Total Synthesis of Vinblastine, Related Natural Products, and Key Analogues and Development of Inspired Methodology Suitable for the Systematic Study of Their Structure–Function Properties
Abstract
Conspectus
Biologically active natural products composed of fascinatingly complex structures are often regarded as not amenable to traditional systematic structure–function studies enlisted in medicinal chemistry for the optimization of their properties beyond what might be accomplished by semisynthetic modification. Herein, we summarize our recent studies on the Vinca alkaloids vinblastine and vincristine, often considered as prototypical members of such natural products, that not only inspired the development of powerful new synthetic methodology designed to expedite their total synthesis but have subsequently led to the discovery of several distinct classes of new, more potent, and previously inaccessible analogues.
With use of the newly developed methodology and in addition to ongoing efforts to systematically define the importance of each embedded structural feature of vinblastine, two classes of analogues already have been discovered that enhance the potency of the natural products >10-fold. In one instance, remarkable progress has also been made on the refractory problem of reducing Pgp transport responsible for clinical resistance with a series of derivatives made accessible only using the newly developed synthetic methodology. Unlike the removal of vinblastine structural features or substituents, which typically has a detrimental impact, the additions of new structural features have been found that can enhance target tubulin binding affinity and functional activity while simultaneously disrupting Pgp binding, transport, and functional resistance. Already analogues are in hand that are deserving of full preclinical development, and it is a tribute to the advances in organic synthesis that they are readily accessible even on a natural product of a complexity once thought refractory to such an approach.
Special Issue
Published as part of the Accounts of Chemical Research special issue “Synthesis, Design, and Molecular Function”.
Conclusions and Outlook
Biographies
Acknowledgment
We gratefully acknowledge the financial support of the National Institutes of Health (CA115526 and CA042056, DLB).
References
This article references 50 other publications.
-
1Noble, R. L.; Beer, C. T.; Cutts, J. H. Role of chance observations in chemotherapy: Vinca rosea Ann. N.Y. Acad. Sci. 1958, 76, 882– 894Google Scholar1https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaG1M%252FlslCltQ%253D%253D&md5=a728fef90a06da248a734bfbed91a985Role of chance observations in chemotherapy: Vinca roseaNOBLE R L; BEER C T; CUTTS J HAnnals of the New York Academy of Sciences (1958), 76 (3), 882-94 ISSN:0077-8923.There is no expanded citation for this reference.
-
2Noble, R. L. Catharanthus roseus (vinca rosea): Importance and value of a chance observation Lloydia 1964, 27, 280– 281Google ScholarThere is no corresponding record for this reference.
-
3Svoboda, G. H.; Nuess, N.; Gorman, M. Alkaloids of Vinca rosea Linn. (Catharanthus roseus G. Don.). V. Preparation and characterization of alkaloids J. Am. Pharm. Assoc. Sci. Ed. 1959, 48, 659– 666Google Scholar3https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF3cXjsVeltw%253D%253D&md5=6946ca8bc3a4e61aac61d48861318ca4Alkaloids of Vinca rosea (Catharanthus roseus). V. Preparation and characterization of alkaloidsSvoboda, Gordon H.; Neuss, Norbert; Gorman, MarvinJournal of the American Pharmaceutical Association, Scientific Edition (1959), 48 (), 659-66CODEN: JAPMA8; ISSN:0095-9553.cf. preceding abstr. The following alkaloids were isolated from V. rosea [m.p., [α]26D (CHCl3), pK'a in 66% HCONMe2 and λ(EtOH) in mμ given]: vindoline, 154-5°, 42°, 5.5, 212, 250, 304; catharanthine, 126-8°, 29.8°, 6.8, 226, 284, 292; vindolinine-2HCl, 210-12° (decompn.), -8° (H2O), 3.3, 7.1,245,300; lochnericine, 190-3° (decompn.), -432°, 4.2, 226, 297, 327; leurosine (I), 202-5° (decompn.), 72°, 5.5, 7.5 (H2O), 214, 259; vincaleukoblastine (II), 211-16° (decompn.), 42° (detd. on the etherate), 5.4, 7.4 (H2O), 214,259; perivine, 180-1°, -121.4°, 7.5, 226,314; virosine, 258-64° (decompn.), -160.5°, 5.85, 226,270. I and II showed activity against P-1534 leukemia in mice.
-
4Neuss, N.; Neuss, M. N. Therapeutic use of bisindole alkaloids from catharanthus. In The Alkaloids; Brossi, A.; Suffness, M., Eds.; Academic: San Diego, CA, 1990; Vol. 37, pp 229– 240.Google ScholarThere is no corresponding record for this reference.
-
5Pearce, H. L. Medicinal chemistry of bisindole alkaloids from Catharanthus. In The Alkaloids; Brossi, A.; Suffness, M., Eds.; Academic: San Diego, CA, 1990; Vol. 37, pp 145– 204.Google ScholarThere is no corresponding record for this reference.
-
6Kuehne, M. E.; Marko, I. Syntheses of vinblastine-type alkaloids. In The Alkaloids; Brossi, A.; Suffness, M., Eds.; Academic: San Diego, CA, 1990; Vol. 37, pp 77– 132.Google ScholarThere is no corresponding record for this reference.
-
7Fahy, J. Modifications in the “upper” velbenamine part of the Vinca alkaloids have major implications for tubulin interacting activities Curr. Pharm. Des. 2001, 7, 1181– 1197Google Scholar7https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmt1enu7s%253D&md5=91da38c20fa29bc51baf55eb6f76c388Modifications in the « upper » or velbenamine part of the Vinca alkaloids have major implications for tubulin interacting activitiesFahy, JacquesCurrent Pharmaceutical Design (2001), 7 (13), 1181-1197CODEN: CPDEFP; ISSN:1381-6128. (Bentham Science Publishers)A review with refs. Vinca alkaloids represent a chem. class of major interest in cancer chemotherapy. The lead compds. vinblastine and vincristine have been employed in clin. practice for more than thirty years and remain widely used to this day. Several hundred derivs. have been synthesized and evaluated for their pharmacol. activities, the majority being modified in the vindoline moiety, bearing several reactive centers. These efforts led to the identification of the amido deriv. vindesine, registered in Europe in 1980 and now available in several countries. Then novel chem. permitted the semisynthesis of derivs. modified in the velbenamine or « upper » part of the mol., creating a new potential in the Vinca alkaloids medicinal chem.: as a result, vinorelbine, obtained by C' ring contraction of anhydrovinblastine, and is now marketed worldwide. Several strategies aimed at the total synthesis of vinblastine derivs. have been investigated, giving the opportunity to design rationally certain compds. Modifications in the D' ring appeared to induce dramatic changes in the tubulin interactions. These observations have been confirmed recently by the identification of unprecedented pharmacol. properties exerted by the novel fluorinated Vinca alkaloid, vinflunine. This review will focus more specifically on derivs. which have been modified in the velbenamine part, with the aim of inducing different chem. and pharmacol. properties.
-
8Potier, P. Synthesis of the antitumor dimeric indole alkaloids from catharanthus species (vinblastine group) J. Nat. Prod. 1980, 43, 72– 86Google Scholar8https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3cXhvFymuro%253D&md5=14aeb1a8af60a9996f94e4df1a6bdcd0Synthesis of the antitumor dimeric indole alkaloids from Catharanthus species (vinblastine group)Potier, PierreJournal of Natural Products (1980), 43 (1), 72-86CODEN: JNPRDF; ISSN:0163-3864.The synthesis of vinblastine alkaloids via a modified Polonovski reaction was reviewed with 49 refs. Norvinblastine alkaloids were also prepd. by this approach.
-
9Kutney, J. P. Plant cell culture combined with chemistry: a powerful route to complex natural products Acc. Chem. Res. 1993, 26, 559– 566Google Scholar9https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXmt1Cgtrg%253D&md5=ff8527ce783979c3d92af16b53bf6bf6Plant cell culture combined with chemistry: a powerful route to complex natural productsKutney, James P.Accounts of Chemical Research (1993), 26 (10), 559-66CODEN: ACHRE4; ISSN:0001-4842.Utilizing specific examples from the author's lab., a summary of the possible avenues of research in which plant cell culture methods combined with chem. can afford interesting routes to biol. active compds. is provided. The results presented illustrate the potential of such an interdisciplinary program and, in particular, reveal that various "shortcomings" in the utilization of plant cell cultures as sometimes expressed by various members of the scientific community (for example, cell line instability, long-term and low-level prodn. of metabolites, etc.) are invalid. With proper selection of methodol., gram-scale prodn. of end products, often in short-term expts. similar to those with microbial systems, can be achieved. The use of semicontinuous fermn. methods, for example, provides an approach of distinct interest in large-scale efficient prodn. of com. important products.
-
10Langlois, N.; Gueritte, F.; Langlois, Y.; Potier, P. Application of a modification of the Polonovski reaction to the synthesis of vinblastine-type alkaloids J. Am. Chem. Soc. 1976, 98, 7017– 7024Google Scholar10https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE28XlvFaqt7s%253D&md5=14ccac703a16223a97e4d6952da6b12eApplication of a modification of the Polonovski reaction to the synthesis of vinblastine-type alkaloidsLanglois, Nicole; Gueritte, Francoise; Langlois, Yves; Potier, PierreJournal of the American Chemical Society (1976), 98 (22), 7017-24CODEN: JACSAT; ISSN:0002-7863.A new C-16-C-21 skeletal fragmentation of ibogane derivs., induced by the modified Polonovski reaction, lead in the presence of aspidospermane derivs. to vinblastine-type compds. with the natural C-16 configuration, such as vindoline and catharanthine N-oxide, which seems necessary for significant antitumor activity. This new method of coupling, which could be the same as the biogenetical pathway, was applied to partial synthesis of naturally occurring antitumor alkaloids of Catharanthus roseus. The circular dichroism distinguished between the natural or unnatural C-16' configurations. Another type of skeletal fragmentation at C-5-C-6, also encountered during this study, was minimized under the exptl. conditions.
-
11Kutney, J. P.; Hibino, T.; Jahngen, E.; Okutani, T.; Ratcliffe, A. H.; Treasurywala, A. M.; Wunderly, S. Total synthesis of indole and dihydroindole alkaloids. IX. Studies on the synthesis of bisindole alkaloids in the vinblastine-vincristine series. The biogenetic approach Helv. Chim. Acta 1976, 59, 2858– 2882Google Scholar11https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2sXhtVKrt7k%253D&md5=a8f9948d39c38288220138df7d62c96eTotal synthesis of indole and dihydroindole alkaloids. IX. Studies on the synthesis of bisindole alkaloids in the vinblastine-vincristine series. The biogenetic approachKutney, James P.; Hibino, Toshihiko; Jahngen, Edwin; Okutani, Tetsuya; Ratcliffe, Arnold H.; Treasurywala, Adi M.; Wunderly, StephenHelvetica Chimica Acta (1976), 59 (8), 2858-83CODEN: HCACAV; ISSN:0018-019X.The reaction of catharanthine N-oxide and vindoline was carried out at various conditions. Under optimum conditions, which involve low temp. in (F3CCO)2O gave 3',4'-dehydrovinblastine I (R1 = R, R2 = CO2Me, R3 = H) as the exclusive product. I (R1 = CO2Me, R2 = R, R3 = H) and I (R1 = R, R2 = CO2Me, R3 = OH) were often isolated. The reaction, which follows the course of a Polonovski fragmentation process, was extended to the N-oxide derivs. of dihydrocatharanthine and decarbomethoxycatharanthine to give bisindole alkaloid derivs.
-
12Kuehne, M. E.; Matson, P. A.; Bornmann, W. G. Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20′-epi-vincovaline J. Org. Chem. 1991, 56, 513– 528Google Scholar12https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXhs1Cmu7k%253D&md5=dbdd7ea7d52b44b9814bc56ce6237925Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20'-epi-vincovalineKuehne, Martin E.; Matson, Patricia A.; Bornmann, William G.Journal of Organic Chemistry (1991), 56 (2), 513-28CODEN: JOCEAH; ISSN:0022-3263.The binary indole-indoline alkaloids vinblastine (I), leurosidine, 20'-epi-vincovaline, and vincovaline, were obtained by coupling of vindoline to the tetracyclic intermediates, e.g. II, followed by redn. and cyclization steps (60% overall yield for these reactions). The intermediates were obtained by enantioselective establishment of C20' through a first-step Sharpless oxidn. and followed by a subsequent diastereomeric sepn. Alternatively, enantioselective control of the key secodine-type cyclization in the reaction sequence provided the tetracyclic intermediates III for coupling to vindoline. Selective generation of the natural or unnatural atropisomeric forms of the alkaloids was achieved through alternative closures of ring D'. The natural products were also obtained from the higher energy atropisomers by conformational inversion on heating. For the vinblastine synthesis, the overall yield was 22%.
-
13Bornmann, W. G.; Kuehne, M. E. A common intermediate providing syntheses of ψ-tabersonine, coronaridine, iboxyphylline, ibophyllidine, vinamidine, and vinblastine J. Org. Chem. 1992, 57, 1752– 1760Google Scholar13https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XhslCnu7k%253D&md5=47a9a9e4d4d55892f78c53fee45cb07bA common intermediate providing syntheses of Ψ-tabersonine, coronaridine, iboxyphylline, ibophyllidine, vinamidine, and vinblastineBornmann, William G.; Kuehne, Martin E.Journal of Organic Chemistry (1992), 57 (6), 1752-60CODEN: JOCEAH; ISSN:0022-3263.Generation of the key tetracyclic intermediates I in 6 steps (42% overall) and subsequent short redn., oxidn., and arylation sequences results in total syntheses of the tile compds., e.g. coronaridine II.
-
14Yokoshima, S.; Ueda, T.; Kobayashi, S.; Sato, A.; Kuboyama, T.; Tokuyama, H.; Fukuyama, T. Stereocontrolled total synthesis of (+)-vinblastine J. Am. Chem. Soc. 2002, 124, 2137– 2139Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xht1eltL8%253D&md5=c3f72b337748b01c2ab90b4ab6e6e12fStereocontrolled total synthesis of (+)-vinblastineYokoshima, Satoshi; Ueda, Toshihiro; Kobayashi, Satoshi; Sato, Ayato; Kuboyama, Takeshi; Tokuyama, Hidetoshi; Fukuyama, TohruJournal of the American Chemical Society (2002), 124 (10), 2137-2139CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A stereocontrolled total synthesis of (+)-vinblastine was accomplished, featuring prepns. of the two indole units (I and II) by means of a novel indole synthesis via radical cyclization of thioanilide, and a stereoselective coupling of these units.
Additionally, see:
Kuboyama, T.; Yokoshima, S.; Tokuyama, H.; Fukuyama, T. Stereocontrolled total synthesis of (+)-vincristine Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 11966– 11970Google Scholar14https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXntFeksr4%253D&md5=91eb430c84061368d23a89d1f5992f25Stereocontrolled total synthesis of (+)-vincristineKuboyama, Takeshi; Yokoshima, Satoshi; Tokuyama, Hidetoshi; Fukuyama, TohruProceedings of the National Academy of Sciences of the United States of America (2004), 101 (33), 11966-11970CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)An efficient total synthesis of (+)-vincristine has been accomplished through a stereoselective coupling of demethylvindoline and the eleven-membered carbomethoxyverbanamine precursor. Demethylvindoline was prepd. by oxidn. of 17-hydroxy-11-methoxytabersonine, followed by regioselective acetylation with mixed anhydride method. Although an initial attempt of coupling by using demethylvindoline formamide was not successful and resulted in recovery of the starting compds., the reaction using demethylvindoline took place smoothly to furnish the desired bisindole product with the correct stereochem. at C18'. After formation of the piperidine ring by sequential removal of the protective groups and intramol. nucleophilic cyclization, the total synthesis of vincristine was completed by formylation of N1. -
15Magnus, P.; Stamford, A.; Ladlow, M. Synthesis of the antitumor bisindole alkaloid vinblastine: diastereoselectivity and solvent effect on the stereochemistry of the crucial C-15-C-18′ bond J. Am. Chem. Soc. 1990, 112, 8210– 8212Google Scholar15https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3cXmtFans7o%253D&md5=75715cea7a43100a60b3287fb27b9df4Synthesis of the antitumor bisindole alkaloid vinblastine: diastereoselectivity and solvent effect on the stereochemistry of the crucial C-15-C-18' bondMagnus, Philip; Stamford, Andrew; Ladlow, MarkJournal of the American Chemical Society (1990), 112 (22), 8210-12CODEN: JACSAT; ISSN:0002-7863.Treatment of pyrrolocarboline I with ClCO2CH2C6H4NO2-p/vindoline/CH3NO2 at -20°C in the presence of 2,6-di-tert-butyl-4-methylpyridine gave the correct 18'(S) stereoisomer II (Q = CO2CH2C6H2NO2-4) which was converted in 3 steps to vinblastine. Of all of the various stereoisomers of I only one gave the correct C-18', C-2' and C-4' abs. stereochem.
-
16Ishikawa, H.; Colby, D. A.; Seto, S.; Va, P.; Tam, A.; Kakei, H.; Rayl, T. J.; Hwang, I.; Boger, D. L. Total synthesis of vinblastine, vincristine, related natural products, and key structural analogues J. Am. Chem. Soc. 2009, 131, 4904– 4916Google Scholar16https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjt1Gqtbw%253D&md5=da33d88f99ec7f3024a4efcf2198736eTotal Synthesis of Vinblastine, Vincristine, Related Natural Products, and Key Structural AnaloguesIshikawa, Hayato; Colby, David A.; Seto, Shigeki; Va, Porino; Tam, Annie; Kakei, Hiroyuki; Rayl, Thomas J.; Hwang, Inkyu; Boger, Dale L.Journal of the American Chemical Society (2009), 131 (13), 4904-4916CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Full details of the development of a direct coupling of catharanthine with vindoline to provide vinblastine (I) are described along with key mechanistic and labeling studies. Following an Fe(III)-promoted coupling reaction initiated by generation of a presumed catharanthine radical cation that undergoes a subsequent oxidative fragmentation and diastereoselective coupling with vindoline, addn. of the resulting reaction mixt. to an Fe(III)-NaBH4/air soln. leads to oxidn. of the C15'-C20' double bond and redn. of the intermediate iminium ion directly providing vinblastine (40-43%) and leurosidine (20-23%), its naturally occurring C20' alc. isomer. The yield of coupled products, which exclusively possess the natural C16' stereochem., approaches or exceeds 80% and the combined yield of the isomeric C20' alcs. is >60%. Preliminary studies of Fe(III)-NaBH4/air oxidn. reaction illustrate a generalizable trisubstituted olefin scope, identify alternatives to O2 trap at the oxidized carbon, provide a unique entry into C20' functionalized vinblastines, and afford initial insights into the obsd. C20' diastereoselectivity. The first disclosure of the use of exo-catharanthine proceeding through Δ19',20'-anhydrovinblastine in such coupling reactions is also detailed with identical stereochem. consequences. Incorporating either a catharanthine N-Me group or a vindoline N-formyl group precludes Fe(III)-promoted coupling, whereas the removal of the potentially key C16 methoxy group of vindoline does not adversely impact the coupling efficiency. Extension of these studies provided a total synthesis of vincristine (II) via N-desmethylvinblastine (also a natural product), 16-desmethoxyvinblastine and 4-desacetoxy-16-desmethoxyvinblastine both of which we can now suggest are likely natural products produced by C. roseus, desacetylvinblastine and 4-desacetoxyvinblastine, as well as a series of key analogs bearing systematic modifications in the vindoline subunit. Their biol. evaluation provided addnl. insights into the key functionality within the vindoline subunit contributing to the activity and sets the foundation on which further, more deep-seated changes in the structures of I and II will be explored in future studies.
-
17Ishikawa, H.; Elliott, G. I.; Velcicky, J.; Choi, Y.; Boger, D. L. Total synthesis of (−)- and ent-(+)-vindoline and related alkaloids J. Am. Chem. Soc. 2006, 128, 10596– 10612Google Scholar17https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xnt12nsLs%253D&md5=38749a412611ea9892da0a1453deff73Total Synthesis of (-)- and ent-(+)-Vindoline and Related AlkaloidsIshikawa, Hayato; Elliott, Gregory I.; Velcicky, Juraj; Choi, Younggi; Boger, Dale L.Journal of the American Chemical Society (2006), 128 (32), 10596-10612CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A concise 11-step total synthesis of (-)- and ent-(+)-vindoline is detailed based on a unique tandem intramol. [4 + 2]/[3 + 2] cycloaddn. cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which three rings and four C-C bonds are formed central to the characteristic pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. As key elements of the scope and stereochem. features of the reaction were defined, a series of related natural products of increasing complexity were prepd. by total synthesis including both enantiomers of minovine, 4-desacetoxy-6,7-dihydrovindorosine, 4-desacetoxyvindorosine, and vindorosine as well as N-methylaspidospermidine. Subsequent extensions of the approach provided both enantiomers of 6,7-dihydrovindoline, 4-desacetoxyvindoline, and 4-desacetoxy-6,7-dihydrovindoline.
-
18Choi, Y.; Ishikawa, H.; Velcicky, J.; Elliott, G. I.; Miller, M. M.; Boger, D. L. Total synthesis of (−)- and ent-(+)-vindoline Org. Lett. 2005, 7, 4539– 4542Google Scholar18https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXpt1Whu74%253D&md5=66153575bab3f154b43c9e5f56b01752Total Synthesis of (-)- and ent-(+)-VindolineChoi, Younggi; Ishikawa, Hayato; Velcicky, Juraj; Elliott, Gregory I.; Miller, Michael M.; Boger, Dale L.Organic Letters (2005), 7 (20), 4539-4542CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)Two exceptionally concise total syntheses of (-)-vindoline (I) and ent-(+)-vindoline are detailed enlisting a diastereoselective tandem [4+2]/[3+2] cycloaddn. of a 1,3,4-oxadiazole. The unique reaction cascade assembles the fully functionalized pentacyclic ring system of vindoline in a single step that forms four C-C bonds and three rings while introducing all requisite functionality and setting all six stereocenters within the central ring including three contiguous and four total quaternary centers.
-
19Yuan, Z.; Ishikawa, H.; Boger, D. L. Total synthesis of natural (−)- and ent-(+)-4-desacetoxy-6,7-dihydrovindorosine and natural and ent-minovine: oxadiazole tandem intramolecular Diels–Alder/1,3-dipolar cycloaddition reaction Org. Lett. 2005, 7, 741– 744Google Scholar19https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslSmuw%253D%253D&md5=2064655c266ccd452f11a22e3a754486Total synthesis of natural (+)- and ent-(-)-4-desacetoxy-6,7-dihydrovindorosine and natural and ent-minovine: oxadiazole tandem intramolecular Diels-Alder/1,3-dipolar cycloaddition reactionYuan, Zhong Qing; Ishikawa, Hayato; Boger, Dale L.Organic Letters (2005), 7 (4), 741-744CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)Efficient and unusually concise total syntheses of both enantiomers of the Aspidosperma alkaloids 4-desacetoxy-6,7-dihydrovindorosine (I) and minovine (II) are detailed. A tandem intramol. Diels-Alder/1,3-dipolar cycloaddn. reaction of the 1,3,4-oxadiazole III, in which three new rings, four new C-C bonds, and five stereocenters are formed, is a key step in the sequence. The availability of optically active material permitted an assessment of the enantiomeric integrity of minovine and the source of its reported unusual optical rotation.
-
20Elliott, G. I.; Velcicky, J.; Ishikawa, H.; Li, Y.; Boger, D. L. Total synthesis of (−)- and ent-(+)-vindorosine: tandem intramolecular Diels–Alder/1,3-dipolar cycloaddition reaction of 1,3,4-oxadiazoles Angew. Chem., Int. Ed. 2006, 45, 620– 622Google ScholarThere is no corresponding record for this reference.
-
21Ishikawa, H.; Boger, D. L. Total synthesis of natural (−)- and ent-(+)-4-desacetoxy-5-desethylvindoline Heterocycles 2007, 72, 95– 102Google ScholarThere is no corresponding record for this reference.
-
22Elliott, G. I.; Fuchs, J. R.; Blagg, B. S. J.; Ishikawa, H.; Tao, H.; Yuan, Z.; Boger, D. L. Intramolecular Diels–Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles J. Am. Chem. Soc. 2006, 128, 10589– 10595Google Scholar22https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xnt12nsLo%253D&md5=754e07e1bcdabfbef4ba4dc5a15911deIntramolecular Diels-Alder/1,3-Dipolar Cycloaddition Cascade of 1,3,4-OxadiazolesElliott, Gregory I.; Fuchs, James R.; Blagg, Brian S. J.; Ishikawa, Hayato; Tao, Houchao; Yuan, Z.-Q.; Boger, Dale L.Journal of the American Chemical Society (2006), 128 (32), 10589-10595CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The intramol. [4 + 2]/[3 + 2] cascade intramol. cycloaddn. of 1,3,4-oxadiazoles, e.g. I (R = H, Me, Me3CSiMe2OCH2, Ph, PhCH2O, CN, MeO2C), to afford polyheterocycles, e.g. II, has been systematically explored and the scope and utility of the reaction have been defined.
-
23Wilkie, G. D.; Elliott, G. I.; Blagg, B. S. J.; Wolkenberg, S. E.; Soenen, D. B.; Miller, M. M.; Pollack, S.; Boger, D. L. Intramolecular Diels–Alder and tandem intramolecular Diels–Alder/1,3-dipolar cycloaddition reactions of 1,3,4-oxadiazoles J. Am. Chem. Soc. 2002, 124, 11292– 11294Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmsFGmu70%253D&md5=413092b5f48d5b5fa3d2bc39baa715feIntramolecular Diels-Alder and Tandem Intramolecular Diels-Alder/1,3-Dipolar Cycloaddition Reactions of 1,3,4-OxadiazolesWilkie, Gordon D.; Elliott, Gregory I.; Blagg, Brian S. J.; Wolkenberg, Scott E.; Soenen, Danielle R.; Miller, Michael M.; Pollack, Scott; Boger, Dale L.Journal of the American Chemical Society (2002), 124 (38), 11292-11294CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Polycycles such as I and II are prepd. by stereoselective intramol. Diels-Alder reactions of indole- and alkene-contg. oxadiazoles such as III and IV followed by loss of nitrogen and stereoselective intramol. [3+2] dipolar cycloaddn. The reactants are prepd. in short sequences from alkene- or indole-contg. carboxylic acids and aminooxadiazoles prepd. by cyclocondensation of oxalylsemicarbazides. Heating in either 1,2-dichlorobenzene at 180° or in 1,3,5-triisopropylbenzene at 230° gives the polycyclic products in 41-87% yields. The geometry of the products is detd. by the alkene geometry and by stereoselective addn. of the indole to the α-face of the intermediate oxonium ylide; this allows up to six stereocenters to be set reliably in a single reaction. Only oxadiazoles undergo stereoselective cycloaddn. reactions; neither thiadiazoles or N-methyltriazoles react at all. One of the substituents on the oxadiazolylamine must be an acyl group for cycloaddn. to occur. Alkynyl-substituted oxadiazoles also undergo cycloaddn. reactions to give fused furans; alkyne equiv. are also effective, such as in the prepn. of V by tandem cycloaddn. and elimination reactions of VI. This reaction sequence provides rapid access to the ring system and substitution pattern of vindoline.
-
24Boger, D. L. Diels–Alder reactions of azadienes Tetrahedron 1983, 39, 2869– 2939Google Scholar24https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2cXjsVChug%253D%253D&md5=c577e1f3bdeb12a2cdcc17c3a25d0bd3Diels-Alder reactions of azadienesBoger, Dale L.Tetrahedron (1983), 39 (18), 2869-939CODEN: TETRAB; ISSN:0040-4020.A review with 203 refs.
-
25Boger, D. L. Diels–Alder reactions of heterocyclic azadienes Chem. Rev. 1986, 86, 781– 793Google ScholarThere is no corresponding record for this reference.
-
26Vukovic, J.; Goodbody, A. E.; Kutney, J. P.; Misawa, M. Production of 3′,4′-anhydrovinblastine: a unique chemical synthesis Tetrahedron 1988, 44, 325– 331Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL1cXkvFensrs%253D&md5=99df6516eb456055d2095d25f3a1d580Production of 3',4'-anhydrovinblastine: a unique chemical synthesisVukovic, J.; Goodbody, A. E.; Kutney, J. P.; Misawa, M.Tetrahedron (1988), 44 (2), 325-31CODEN: TETRAB; ISSN:0040-4020.Preliminary investigations have led to the discovery that ferric ion can couple catharanthine and vindoline in aq. acidic media to produce 3',4'-anhydrovinblastine as the major product. A conversion of 77% could be realized under optimized conditions.
-
27Ishikawa, H.; Colby, D. A.; Boger, D. L. Direct coupling of catharanthine and vindoline to provide vinblastine: total synthesis of (+)- and ent-(−)-vinblastine J. Am. Chem. Soc. 2008, 130, 420– 421Google Scholar27https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVehu7%252FK&md5=f06c9711d4ccb2dc4c45bf79120126feDirect Coupling of Catharanthine and Vindoline to Provide Vinblastine: Total Synthesis of (+)- and ent-(-)-VinblastineIshikawa, Hayato; Colby, David A.; Boger, Dale L.Journal of the American Chemical Society (2008), 130 (2), 420-421CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A direct coupling of catharanthine I with vindoline II to provide vinblastine III is detailed along with key mechanistic and labeling studies. Following an Fe(III)-promoted coupling reaction initiated by generation of a presumed catharanthine amine radical cation that undergoes a subsequent oxidative fragmentation and diastereoselective coupling with vindoline, addn. of the resulting reaction mixt. to an Fe(III)-NaBH4/air soln. leads to oxidn. of the C15'-C21' double bond and redn. of the intermediate iminium ion directly providing vinblastine (43%) and leurosidine (23%), its naturally occurring C21' alc. isomer. The yield of coupled products, which exclusively possess the natural C16' stereochem., approaches or exceeds 80%, and the combined yield of the isomeric C21' alcs. is 66%.
-
28Sasaki, Y.; Kato, D.; Boger, D. L. Asymmetric total synthesis of vindorosine, vindoline, and key vinblastine analogues J. Am. Chem. Soc. 2010, 132, 13533– 13544Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtV2kur3M&md5=1238182ac0bd1cf56d5354492d316014Asymmetric Total Synthesis of Vindorosine, Vindoline, and Key Vinblastine AnaloguesSasaki, Yoshikazu; Kato, Daisuke; Boger, Dale L.Journal of the American Chemical Society (2010), 132 (38), 13533-13544CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Vindoline I (R = MeO) and vindorosine I (R = H) are prepd. stereoselectively using the tandem intramol. [4 + 2]/[3 + 2] cycloaddn. cascades of indole-substituted 1,3,4-oxadiazoleamides such as II (R1 = H, PhCH2O; R2 = PhCH2O, H; MOM = methoxymethyl) to give hexacycles such as III (R1 = H, PhCH2O; R2 = PhCH2O, H) as the key steps. II (R1 = H, PhCH2O; R2 = PhCH2O, H) are prepd. in six or nine steps from protected D-serine and D-aspartic acid moieties, resp.; the methoxymethoxymethyl moiety controls the facial selectivity of the initiating Diels-Alder reactions of II and sets the abs. stereochem. of the remaining six stereocenters in the cascade cycloadducts. A ring expansion reaction is developed to generate the 6-membered ring with appropriate functionality for introduction of the Δ6,7-double bond found in I. I (R = MeO) and related analogs generated in its synthesis are converted to vinblastine analogs by iron-mediated oxidative coupling reactions with catharanthine sulfate; the activities of the vinblastine analogs against murine leukemia and drug-susceptible and drug-resistant human colon cancer cell lines are detd. Analogs of vinblastine lacking the vinblastine Δ6,7-double bond inhibit cancer cells only at concns. 100-fold greater than that at which vinblastine inhibits the same cancer cells. The structures of selected intermediates in the prepn. of I (R = H, MeO) or of their enantiomers are detd. by X-ray crystallog.
-
29Kato, D.; Sasaki, Y.; Boger, D. L. Asymmetric total synthesis of vindoline J. Am. Chem. Soc. 2010, 132, 3685– 3687Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXisVOqsrs%253D&md5=26f4d78eb3595ec77264863543c33c5cAsymmetric Total Synthesis of VindolineKato, Daisuke; Sasaki, Yoshikazu; Boger, Dale L.Journal of the American Chemical Society (2010), 132 (11), 3685-3687CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A concise asym. total synthesis of (-)-vindoline (I) is detailed based on a tandem intramol. [4+2]/[3+2] cycloaddn. cascade of a 1,3,4-oxadiazole II inspired by the natural product structure, in which the tether linking the initiating dienophile and oxadiazole bears a chiral substituent that controls the facial selectivity of the initiating Diels-Alder reaction and sets abs. stereochem. of the remaining six stereocenters in the cascade cycloadduct. This key reaction introduces three rings and four C-C bonds central to the pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. Implementation of the approach also required the development of a unique ring expansion reaction to provide a six-membered ring suitably functionalized for introduction of the Δ-double bond found in the core structure of vindoline and defined our use of a protected hydroxymethyl group as the substituent used to control the stereochem. course of the cycloaddn. cascade.
-
30Kuehne, M. E.; Bornmann, W. G.; Marko, I.; Qin, Y.; Le Boulluec, K. L.; Frasier, D. A.; Xu, F.; Malamba, T.; Ensinger, C. L.; Borman, L. S.; Huot, A. E.; Exon, C.; Bizzarro, F. T.; Cheung, J. B.; Bane, S. L. Syntheses and biological evaluation of vinblastine congeners Org. Biomol. Chem. 2003, 1, 2120– 2136Google ScholarThere is no corresponding record for this reference.
-
31Miyazaki, T.; Yokoshima, S.; Simizu, S.; Osada, H.; Tokuyama, H.; Fukuyama, T. Synthesis of (+)-vinblastine and its analogues Org. Lett. 2007, 9, 4737– 4740Google Scholar31https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtFKhtbbN&md5=69b307f1a999da3091938428fbc98072Synthesis of (+)-Vinblastine and Its AnaloguesMiyazaki, Tohru; Yokoshima, Satoshi; Simizu, Siro; Osada, Hiroyuki; Tokuyama, Hidetoshi; Fukuyama, TohruOrganic Letters (2007), 9 (23), 4737-4740CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)A synthetic route to vinblastine and its analogs with an ethynyl group, which features a stereoselective coupling of an 11-membered key intermediate with vindoline, is described. Transformations of the alkynyl moiety including a partial redn. as well as a Sonogashira coupling furnished a variety of analogs.
-
32Voss, M. E.; Ralph, J. M.; Xie, D.; Manning, D. D.; Chen, X.; Frank, A. J.; Leyhane, A. J.; Liu, L.; Stevens, J. M.; Budde, C.; Surman, M. D.; Friedrich, T.; Peace, D.; Scott, I. L.; Wolf, M.; Johnson, R. Synthesis and SAR of vinca alkaloid analogues Bioorg. Med. Chem. Lett. 2009, 19, 1245– 1249Google Scholar32https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXit1Wru74%253D&md5=5e1b81b6ea85a9fbfc10f2f8cca61ce4Synthesis and SAR of Vinca alkaloid analogsVoss, Matthew E.; Ralph, Jeffery M.; Xie, Dejian; Manning, David D.; Chen, Xinchao; Frank, Anthony J.; Leyhane, Andrew J.; Liu, Lei; Stevens, Jason M.; Budde, Cheryl; Surman, Matthew D.; Friedrich, Thomas; Peace, Denise; Scott, Ian L.; Wolf, Mark; Johnson, RandallBioorganic & Medicinal Chemistry Letters (2009), 19 (4), 1245-1249CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)Versatile intermediates 12'-iodovinblastine, 12'-iodovincristine and 11'-iodovinorelbine I [R1 = Me, R3' = H, R4' = OH-β, R12' = iodo, X7' = (CH2)2; R1 = CHO, R3' = H, R4' = OH-β, R12' = iodo, X7' = (CH2)2; R1 = Me, R3'R4' = bond, R12' = iodo, X7' = CH2, resp.] were utilized as substrates for transition metal based chem. which led to the prepn. of novel analogs of the Vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products and the SAR based upon HeLa and MCF-7 cell toxicity assays was presented. Selected analogs I [R1 = Me, R3' = H, R4' = OH-β, R12' = Me, SMe, X7' = (CH2)2] showed promising anticancer activity in the P388 murine leukemia model.
-
33Gherbovet, O.; Coderch, C.; Alvarez, M. C. G.; Bignon, J.; Thoret, S.; Martin, M.-T.; Guéritte, F.; Gago, F.; Roussi, F. Synthesis and biological evaluation of a new series of highly functionalized 7′-homo-anhydrovinblastine derivatives J. Med. Chem. 2013, 56, 6088– 6100Google ScholarThere is no corresponding record for this reference.
-
34Va, P.; Campbell, E. L.; Robertson, W. M.; Boger, D. L. Total synthesis and evaluation of a key series of C5-substituted vinblastine derivatives J. Am. Chem. Soc. 2010, 132, 8489– 8495Google Scholar34https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmvFarsrY%253D&md5=32a2dee454ee115192b93fa7764a44afTotal Synthesis and Evaluation of a Key Series of C5-Substituted Vinblastine DerivativesVa, Porino; Campbell, Erica L.; Robertson, William M.; Boger, Dale L.Journal of the American Chemical Society (2010), 132 (24), 8489-8495CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Desacetoxyvinblastine derivs. such as I [R = H, Me, Et, EtCH2, HC≡C, H2C:CH, HOCH2, OHC, (S)-R1OCCH2CH(OR1), Me3CMe2SiC≡C; R1 = H, EtCH2CO] (vinblastine analogs) with varying C5 substituents are prepd. stereoselectively using the intramol. domino [4+2]/[3+2] cycloaddn. reactions of (alkenoyl)(indoleethyl)amino oxazadiazolecarboxylates II (R = H, Me, EtCH2, HC≡C) to form the vindoline analogs III (R = H, Me, EtCH2, HC≡C) and the stereoselective biomimetic oxidative coupling reactions of vindoline analogs with catharanthine sulfate as the key steps. The antitumor activities of I [R = H, Me, Et, EtCH2, HC≡C, H2C:CH, HOCH2, OHC, (S)-R1OCCH2CH(OR1), Me3CMe2SiC≡C; R1 = H, EtCH2CO], epimeric leurosidine and anhydrovinblastine analogs generated in the oxidative coupling step with catharanthine sulfate, and lactone and dehydrovindoline-contg. analogs are detd. in human cell lines. The tubulin binding site surrounding the C5 substituent of vinblastine analogs is exquisitely sensitive to the presence, shape, and polarity of the substituent; only the vinblastine analog I (R = Me) has anticancer activity approaching that obsd. with the vinblastine analog I (R = Et) with the Et group present in vinblastine.
-
35Schleicher, K. D.; Sasaki, Y.; Tam, A.; Kato, D.; Duncan, K. K.; Boger, D. L. Total synthesis and evaluation of vinblastine analogues containing systematic deep-seated modifications in the vindoline subunit ring system: core redesign J. Med. Chem. 2013, 56, 483– 495Google Scholar35https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvVKhurrO&md5=1a7addebed643550c8828ef70c155480Total Synthesis and Evaluation of Vinblastine Analogues Containing Systematic Deep-Seated Modifications in the Vindoline Subunit Ring System: Core RedesignSchleicher, Kristin D.; Sasaki, Yoshikazu; Tam, Annie; Kato, Daisuke; Duncan, Katharine K.; Boger, Dale L.Journal of Medicinal Chemistry (2013), 56 (2), 483-495CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)The total synthesis of a systematic series of vinblastine analogs that contain deep-seated structural modifications to the core ring system of the lower vindoline subunit is described. Complementary to the vindoline 6,5 DE ring system, compds. with 5,5, 6,6, and the reversed 5,6 membered DE ring systems were prepd. Both the natural cis and unnatural trans 6,6-membered ring systems proved accessible, with the latter representing a surprisingly effective class for analog design. Following Fe(III)-promoted coupling with catharanthine and in situ oxidn. to provide the corresponding vinblastine analogs, their evaluation provided unanticipated insights into how the structure of the vindoline subunit contributes to activity. Two potent analogs (I and II) possessing two different unprecedented modifications to the vindoline subunit core architecture were discovered that matched the potency of the comparison natural products and both lack the 6,7-double bond whose removal in vinblastine leads to a 100-fold drop in activity.
-
36Leggans, E. K.; Barker, T. J.; Duncan, K. K.; Boger, D. L. Iron(III)/NaBH4-mediated additions to unactivated alkenes: synthesis of novel 20′-vinblastine analogues Org. Lett. 2012, 14, 1428– 1431Google Scholar36https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XivVOnsrg%253D&md5=954aa67e2b5d5b7f9ce2ac8b02c8857aIron(III)/NaBH4-Mediated Additions to Unactivated Alkenes: Synthesis of Novel 20'-Vinblastine AnaloguesLeggans, Erick K.; Barker, Timothy J.; Duncan, Katharine K.; Boger, Dale L.Organic Letters (2012), 14 (6), 1428-1431CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)An Fe(III)/NaBH4-mediated reaction for the functionalization of unactivated alkenes is described defining the alkene substrate scope, establishing the exclusive Markovnikov addn., exploring a range of free radical traps, examg. the Fe(III) salt and initiating hydride source, introducing H2O-cosolvent mixts., and exploring catalytic variants. Its use led to the prepn. of a novel, potent, and previously inaccessible C20'-vinblastine analog, I [X = NHCONHCOCCl3, NHCONH2, NHCSNH2].
-
37Leggans, E. K.; Duncan, K. K.; Barker, T. J.; Schleicher, K. D.; Boger, D. L. A remarkable series of vinblastine analogues displaying enhanced activity and an unprecedented tubulin binding steric tolerance: C20′ urea derivatives J. Med. Chem. 2013, 56, 628– 639Google Scholar37https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvVCqs7fJ&md5=3af29fd43a2de5b0d6bcc7f79f5ce280A Remarkable Series of Vinblastine Analogues Displaying Enhanced Activity and an Unprecedented Tubulin Binding Steric Tolerance: C20' Urea DerivativesLeggans, Erick K.; Duncan, Katharine K.; Barker, Timothy J.; Schleicher, Kristin D.; Boger, Dale L.Journal of Medicinal Chemistry (2013), 56 (3), 628-639CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)A systematic series of previously inaccessible key C20' urea and thiourea derivs. of vinblastine were prepd. from 20'-aminovinblastine that was made accessible through a unique Fe(III)/NaBH4-mediated alkene functionalization reaction of anhydrovinblastine. Their examn. defined key structural features of the urea-based analogs that contribute to their properties and provided derivs. that match or exceed the potency of vinblastine by as much as 10-fold in cell-based functional assays, which is directly related to their relative tubulin binding affinity. In contrast to expectations based on apparent steric constraints of the tubulin binding site surrounding the vinblastine C20' center depicted in an X-ray cocrystal structure, remarkably large C20' urea derivs. are accommodated.
-
38Barker, T. J.; Duncan, K. K.; Otrubova, K.; Boger, D. L. Potent vinblastine C20′ ureas displaying additionally improved activity against a vinblastine-resistant cancer cell line ACS Med. Chem. Lett. 2013, 4, 985– 988Google ScholarThere is no corresponding record for this reference.
-
39Tam, A.; Gotoh, H.; Robertson, W. M.; Boger, D. L. Catharanthine C16 substituent effects on the biomimetic coupling with vindoline: preparation and evaluation of a key series of vinblastine analogues Bioorg. Med. Chem. Lett. 2010, 20, 6408– 6410Google Scholar39https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlSms7jI&md5=11d7a0b077fac4cfbdf58d862a885d90Catharanthine C16 substituent effects on the biomimetic coupling with vindoline: Preparation and evaluation of a key series of vinblastine analoguesTam, Annie; Gotoh, Hiroaki; Robertson, William M.; Boger, Dale L.Bioorganic & Medicinal Chemistry Letters (2010), 20 (22), 6408-6410CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)The examn. of the catharanthine C16 substituent effects on the Fe(III)-promoted biomimetic coupling reaction with vindoline is detailed, confirming the importance of the presence of a C16 electron-withdrawing substituent, and establishing an unanticipated unique role (>10-fold) that the C16 Me ester plays in the expression of the natural product properties. Thus, replacement of the vinblastine C16' Me ester with an Et ester (10-fold), a cyano group (100-fold), an aldehyde (100-fold), a hydroxymethyl group (1000-fold) or a primary carboxamide (>1000-fold) led to surprisingly large redns. in cytotoxic activity.
-
40Gotoh, H.; Duncan, K. K.; Robertson, W. M.; Boger, D. L. 10′-Fluorovinblastine and 10′-fluorovincristine: synthesis of a key series of modified Vinca alkaloids ACS Med. Chem. Lett. 2011, 2, 948– 952Google ScholarThere is no corresponding record for this reference.
-
41Gotoh, H.; Sears, J. E.; Eschenmoser, A.; Boger, D. L. New insights into the mechanism and an expanded scope of the Fe(III)-mediated vinblastine coupling reaction J. Am. Chem. Soc. 2012, 134, 13240– 13243Google Scholar41https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFChtL7E&md5=375df8d7c8c4e1ed4d3ee15f7fee371dNew Insights into the Mechanism and an Expanded Scope of the Fe(III)-Mediated Vinblastine Coupling ReactionGotoh, Hiroaki; Sears, Justin E.; Eschenmoser, Albert; Boger, Dale L.Journal of the American Chemical Society (2012), 134 (32), 13240-13243CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A definition of the scope of arom. substrates that participate with catharanthine in an Fe(III)-mediated coupling reaction, an examn. of the key structural features of catharanthine required for participation in the reaction, and the development of a generalized indole functionalization reaction that bears little structural relationship to catharanthine itself are detailed. In addn. to providing insights into the mechanism of the Fe(III)-mediated coupling reaction of catharanthine with vindoline suggesting the reaction conducted in acidic aq. buffer may be radical mediated, the studies provide new opportunities for the prepn. of previously inaccessible vinblastine analogs and define powerful new methodol. for the synthesis of indole-contg. natural and unnatural products.
-
42
We thank Gregory Vite and Robert Borzilleri for arranging and overseeing this assessment and Craig Fairchild, Kathy Johnson, and Russell Peterson for conducting the testing at Bristol–Myers Squibb.
There is no corresponding record for this reference. -
43Gigant, B.; Wang, C.; Ravelli, R. B. G.; Roussi, F.; Steinmetz, M. O.; Curmi, P. A.; Sobel, A.; Knossow, M. Structural basis for the regulation of tublin by vinblastine Nature 2005, 435, 519– 522Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXksVeisrc%253D&md5=25451d6a11a9626c4baa02890b16f6aeStructural basis for the regulation of tubulin by vinblastineGigant, Benoit; Wang, Chunguang; Ravelli, Raimond B. G.; Roussi, Fanny; Steinmetz, Michel O.; Curmi, Patrick A.; Sobel, Andre; Knossow, MarcelNature (London, United Kingdom) (2005), 435 (7041), 519-522CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Vinblastine is one of several tubulin-targeting Vinca alkaloids that have been responsible for many chemotherapeutic successes since their introduction in the clinic as antitumor drugs. In contrast with the two other classes of small tubulin-binding mols. (Taxol and colchicine), the binding site of vinblastine is largely unknown and the mol. mechanism of this drug has remained elusive. Here we report the x-ray structure of vinblastine bound to tubulin in a complex with the RB3 protein stathmin-like domain (RB3-SLD). Vinblastine introduces a wedge at the interface of two tubulin mols. and thus interferes with tubulin assembly. Together with electron microscopical and biochem. data, the structure explains vinblastine-induced tubulin self-assocn. into spiral aggregates at the expense of microtubule growth. It also shows that vinblastine and the amino-terminal part of RB3-SLD binding sites share a hydrophobic groove on the α-tubulin surface that is located at an intermol. contact in microtubules. This is an attractive target for drugs designed to perturb microtubule dynamics by interfacial interference, for which tubulin seems ideally suited because of its propensity to self-assoc.
-
44Iwasaki, K.; Wan, K. K.; Oppedisano, A.; Crossley, S. W. M.; Shenvi, R. A. Simple, chemoselective hydrogenation with thermodynamic stereocontrol J. Am. Chem. Soc. 2014, 136, 1300– 1303Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXotVeksA%253D%253D&md5=cad8e944cc88b12006aeddac5323b186Simple, Chemoselective Hydrogenation with Thermodynamic StereocontrolIwasaki, Kotaro; Wan, Kanny K.; Oppedisano, Alberto; Crossley, Steven W. M.; Shenvi, Ryan A.Journal of the American Chemical Society (2014), 136 (4), 1300-1303CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Few methods permit the hydrogenation of alkenes to a thermodynamically favored configuration when steric effects dictate the alternative trajectory of hydrogen delivery. Dissolving metal redn. achieves this control, but with extremely low functional group tolerance. Here we demonstrate a catalytic hydrogenation of alkenes that affords the thermodn. alkane products with remarkably broad functional group compatibility and rapid reaction rates at std. temp. and pressure.
Also see:
Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXotVGjtg%253D%253D&md5=90592331a16f989ea72607e5172c09b8A Practical and Catalytic Reductive Olefin CouplingLo, Julian C.; Yabe, Yuki; Baran, Phil S.Journal of the American Chemical Society (2014), 136 (4), 1304-1307CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)In the presence of Fe(acac)3 and phenylsilane, dienes with one electron-deficient alkene moiety such as methylpentenylcyclohexenone I underwent chemoselective (and in some cases stereoselective) reductive cyclization/coupling reactions in ethanol or ethanol/ethylene glycol mixts. to give cyclization products such as cis-decalone II regioselectively in 60-97% yields. Under similar conditions, alkenes such as 1-methyl-1-cyclohexene underwent regioselective reductive coupling with electron-deficient alkenes to give products such as III (R = MeCO, MeO2C, Me2NCO, NC, PhSO2; R1 = H, MeO2C) in 34-81% yields. Unactivated olefins were joined directly to electron-deficient olefins in both intra- and intermol. settings to generate hindered bicyclic systems, vicinal quaternary centers, and cyclopropanes which would be difficult or perhaps impossible to access using other methods; the reductive coupling reactions were insensitive to oxygen and moisture. -
45Barker, T. J.; Boger, D. L. Fe(III)/NaBH4-mediated free radical hydrofluorination of unactivated alkenes J. Am. Chem. Soc. 2012, 134, 13588– 13591Google Scholar45https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFClurnP&md5=9e25b202126788582c1d2f174f43e0ebFe(III)/NaBH4-mediated free radical hydrofluorination of unactivated alkenesBarker, Timothy J.; Boger, Dale L.Journal of the American Chemical Society (2012), 134 (33), 13588-13591CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A powerful Fe(III)/NaBH4-mediated free radical hydrofluorination of unactivated alkenes is disclosed using Selectfluor reagent as a source of fluorine and resulting in exclusive Markovnikov addn. In contrast to the traditional and unmanageable free radical hydrofluorination of alkenes, the Fe(III)/NaBH4-mediated reaction is conducted under exceptionally mild reaction conditions (0 °C, 5 min, CH3CN/H2O). The reaction can be conducted open to the air and with water as a cosolvent and demonstrates an outstanding substrate scope and functional group tolerance.
-
46Boger, D. L.; Brotherton, C. E. Total synthesis of azafluoranthene alkaloids: rufescine and imelutine J. Org. Chem. 1984, 49, 4050– 4055Google ScholarThere is no corresponding record for this reference.
-
47Duflos, A.; Kruczynski, A.; Baret, J.-M. Novel aspects of natural and modified Vinca alkaloids Curr. Med. Chem., Anti-Cancer Agents 2002, 2, 55– 75Google ScholarThere is no corresponding record for this reference.
-
48Campbell, E. L.; Skepper, C. K.; Sankar, K.; Duncan, K. K.; Boger, D. L. Transannular Diels–Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles: total synthesis of a unique set of vinblastine analogues Org. Lett. 2013, 15, 5306– 5309Google ScholarThere is no corresponding record for this reference.
-
49Roepke, J.; Salim, V.; Wu, M.; Thamm, A. M. K.; Murata, J.; Ploss, K.; Boland, W.; De Luca, V. Vinca drug components accumulate exclusively in leaf exudates of Madagascar periwinkle Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 15287– 15292Google ScholarThere is no corresponding record for this reference.
-
50Once in a while you receive a valued gift if you ask the right question at the right time. Personal communication: Otis, Hutchinson, KS (1971) .Google ScholarThere is no corresponding record for this reference.
Cited By
This article is cited by 150 publications.
- Bowen Zhang, Frederik R. Erb, Aristidis Vasilopoulos, Eric A. Voight, Erik J. Alexanian. General Synthesis of N-Alkylindoles from N,N-Dialkylanilines via [4 + 1] Annulative Double C–H Functionalization. Journal of the American Chemical Society 2023, 145 (49) , 26540-26544. https://doi.org/10.1021/jacs.3c10751
- Luo-Rong Yuan, Shun-Jun Ji, Xiao-Ping Xu. Coupling-Spirocyclization Cascade of Tryptamine-Derived Isocyanides with Iodonium Ylides and Despirocyclization Reactions. Organic Letters 2023, 25 (43) , 7858-7862. https://doi.org/10.1021/acs.orglett.3c03090
- Rui-Han Niu, Jing Zhang, Ru-Yuan Zhao, Quan-Jian Luo, Jin-Heng Li, Bo Sun. Cobalt(III)-Catalyzed Directed C-7 Selective C–H Alkynylation of Indolines with Bromoalkynes. Organic Letters 2023, 25 (29) , 5411-5415. https://doi.org/10.1021/acs.orglett.3c01584
- Rimei Zheng, Aimin Xu, Tianyuan Zhang, Pei Li, Maoqing Shi, Shanliang Dong, Wenhao Hu, Yu Qian. Asymmetric Acyclic 1,3-Difunctionalization of Vinyl Carbenes via Site-Selective Vinylogous Mannich-Type Interception of Oxonium Ylides. Organic Letters 2023, 25 (29) , 5509-5514. https://doi.org/10.1021/acs.orglett.3c01983
- Assia Chebieb, Young Gyu Kim, Jin Kun Cha. Synthesis of Indoles from o-Haloanilines. The Journal of Organic Chemistry 2023, 88 (14) , 10164-10170. https://doi.org/10.1021/acs.joc.3c01047
- Cong Chen, Jing Chen, Han Wang, Ze-Feng Xu, Shengguo Duan, Chuan-Ying Li. Catalyst-Free Synthesis of Polycyclic Spiroindolines by Cascade Reaction of 3-(2-Isocyanoethyl)indoles with 1-Sulfonyl-1,2,3-triazoles. The Journal of Organic Chemistry 2023, 88 (13) , 9543-9553. https://doi.org/10.1021/acs.joc.3c00800
- Alexander W. Rand, Kevin J. Gonzalez, Christopher E. Reimann, Scott C. Virgil, Brian M. Stoltz. Total Synthesis of Strempeliopidine and Non-Natural Stereoisomers through a Convergent Petasis Borono–Mannich Reaction. Journal of the American Chemical Society 2023, 145 (13) , 7278-7287. https://doi.org/10.1021/jacs.2c13146
- Xiangji Yang, Kemiao Hong, Sujie Zhang, Zhijing Zhang, Su Zhou, Jingjing Huang, Xinfang Xu, Wenhao Hu. Asymmetric Three-Component Reaction of Two Diazo Compounds and Hyrdroxylamine Derivatives for the Access to Chiral α-Alkoxy-β-amino-carboxylates. ACS Catalysis 2022, 12 (19) , 12302-12309. https://doi.org/10.1021/acscatal.2c02541
- Wen-Bin Cao, Jian-Dong Zhang, Meng-Meng Xu, Hua-Wei Liu, Hai-Yan Li, Xiao-Ping Xu, Shun-Jun Ji. Syn-Stereoselective C3-Spirocyclization and C2-Amination of 3-(2-Isocyanoethyl)indole Using C,N-Cyclic Azomethine Imines. Organic Letters 2022, 24 (25) , 4620-4624. https://doi.org/10.1021/acs.orglett.2c01736
- Kristen M. Flynn, In-Soo Myeong, Taylor Pinto, Mohammad Movassaghi. Total Synthesis of (−)-Voacinol and (−)-Voacandimine C. Journal of the American Chemical Society 2022, 144 (20) , 9126-9131. https://doi.org/10.1021/jacs.2c03057
- Jiajun Zhang, Srinivas R. Paladugu, Rachel M. Gillard, Anindya Sarkar, Dale L. Boger. Tris(4-bromophenyl)aminium Hexachloroantimonate-Mediated Intermolecular C(sp2)–C(sp3) Free Radical Coupling of Vindoline with β-Ketoesters and Related Compounds. Journal of the American Chemical Society 2022, 144 (1) , 495-502. https://doi.org/10.1021/jacs.1c10971
- Hai-Jiao Long, Yin-Long Li, Bing-Qian Zhang, Wen-Ying Xiao, Xiao-Ying Zhang, Ling He, Jun Deng. Asymmetric Bromoaminocyclization and Desymmetrization of Cyclohexa-1,4-dienes through Anion Phase-Transfer Catalysis. Organic Letters 2021, 23 (21) , 8153-8157. https://doi.org/10.1021/acs.orglett.1c02817
- Fei Zhao, Jin Qiao, Yangbin Lu, Xiaoning Zhang, Long Dai, Siyu Liu, Hangcheng Ni, Xiuwen Jia, Xiaowei Wu, Shiyao Lu. Redox-Neutral Rhodium(III)-Catalyzed Chemospecific and Regiospecific [4+1] Annulation between Indoles and Alkenes for the Synthesis of Functionalized Imidazo[1,5-a]indoles. The Journal of Organic Chemistry 2021, 86 (15) , 10591-10607. https://doi.org/10.1021/acs.joc.1c01256
- Sharna-kay Daley, Geoffrey A. Cordell. Biologically Significant and Recently Isolated Alkaloids from Endophytic Fungi. Journal of Natural Products 2021, 84 (3) , 871-897. https://doi.org/10.1021/acs.jnatprod.0c01195
- Bijay Shrestha, Brennan T. Rose, Casey L. Olen, Aaron Roth, Adon C. Kwong, Yang Wang, Scott E. Denmark. A Unified Strategy for the Asymmetric Synthesis of Highly Substituted 1,2-Amino Alcohols Leading to Highly Substituted Bisoxazoline Ligands. The Journal of Organic Chemistry 2021, 86 (4) , 3490-3534. https://doi.org/10.1021/acs.joc.0c02899
- Christopher Gartshore, Shinji Tadano, Prem B. Chanda, Anindya Sarkar, Naidu S. Chowdari, Sanjeev Gangwar, Qian Zhang, Gregory D. Vite, Jelena Momirov, Dale L. Boger. Total Synthesis of Meayamycin and O-Acyl Analogues. Organic Letters 2020, 22 (21) , 8714-8719. https://doi.org/10.1021/acs.orglett.0c03308
- Anna E. Cholewczynski, Peyton C. Williams, Joshua G. Pierce. Stereocontrolled Synthesis of (±)-Melokhanine E via an Intramolecular Formal [3 + 2] Cycloaddition. Organic Letters 2020, 22 (2) , 714-717. https://doi.org/10.1021/acs.orglett.9b04546
- Byron A. Boon, Dale L. Boger. Triarylaminium Radical Cation Promoted Coupling of Catharanthine with Vindoline: Diastereospecific Synthesis of Anhydrovinblastine and Reaction Scope. Journal of the American Chemical Society 2019, 141 (36) , 14349-14355. https://doi.org/10.1021/jacs.9b06968
- Jiajun Zhang, Vyom Shukla, Dale L. Boger. Inverse Electron Demand Diels–Alder Reactions of Heterocyclic Azadienes, 1-Aza-1,3-Butadienes, Cyclopropenone Ketals, and Related Systems. A Retrospective. The Journal of Organic Chemistry 2019, 84 (15) , 9397-9445. https://doi.org/10.1021/acs.joc.9b00834
- Yongyan Zhu, Ruixuan Liu, Haoji Huang, Quanhong Zhu. Vinblastine-Loaded Nanoparticles with Enhanced Tumor-Targeting Efficiency and Decreasing Toxicity: Developed by One-Step Molecular Imprinting Process. Molecular Pharmaceutics 2019, 16 (6) , 2675-2689. https://doi.org/10.1021/acs.molpharmaceut.9b00243
- Deepali Waghray, Qinghai Zhang. Inhibit or Evade Multidrug Resistance P-Glycoprotein in Cancer Treatment. Journal of Medicinal Chemistry 2018, 61 (12) , 5108-5121. https://doi.org/10.1021/acs.jmedchem.7b01457
- Christopher M. Glinkerman, Dale L. Boger. Synthesis, Characterization, and Rapid Cycloadditions of 5-Nitro-1,2,3-triazine. Organic Letters 2018, 20 (9) , 2628-2631. https://doi.org/10.1021/acs.orglett.8b00825
- Emma King-Smith, Christian R. Zwick, III, and Hans Renata . Applications of Oxygenases in the Chemoenzymatic Total Synthesis of Complex Natural Products. Biochemistry 2018, 57 (4) , 403-412. https://doi.org/10.1021/acs.biochem.7b00998
- Dale L. Boger . The Difference a Single Atom Can Make: Synthesis and Design at the Chemistry–Biology Interface. The Journal of Organic Chemistry 2017, 82 (23) , 11961-11980. https://doi.org/10.1021/acs.joc.7b02088
- Stephen F. Martin . Natural Products and Their Mimics as Targets of Opportunity for Discovery. The Journal of Organic Chemistry 2017, 82 (20) , 10757-10794. https://doi.org/10.1021/acs.joc.7b01368
- Joshua E. Zweig, Daria E. Kim, and Timothy R. Newhouse . Methods Utilizing First-Row Transition Metals in Natural Product Total Synthesis. Chemical Reviews 2017, 117 (18) , 11680-11752. https://doi.org/10.1021/acs.chemrev.6b00833
- John C. Lukesh, III, Daniel W. Carney, Huijun Dong, R. Matthew Cross, Vyom Shukla, Katharine K. Duncan, Shouliang Yang, Daniel M. Brody, Manuela M. Brütsch, Aleksandar Radakovic, and Dale L. Boger . Vinblastine 20′ Amides: Synthetic Analogues That Maintain or Improve Potency and Simultaneously Overcome Pgp-Derived Efflux and Resistance. Journal of Medicinal Chemistry 2017, 60 (17) , 7591-7604. https://doi.org/10.1021/acs.jmedchem.7b00958
- Nengzhong Wang, Shuo Du, Dong Li, and Xuefeng Jiang . Divergent Asymmetric Total Synthesis of (+)-Vincadifformine, (−)-Quebrachamine, (+)-Aspidospermidine, (−)-Aspidospermine, (−)-Pyrifolidine, and Related Natural Products. Organic Letters 2017, 19 (12) , 3167-3170. https://doi.org/10.1021/acs.orglett.7b01292
- Haosen Yuan, Zhixian Guo, and Tuoping Luo . Synthesis of (+)-Lysergol and Its Analogues To Assess Serotonin Receptor Activity. Organic Letters 2017, 19 (3) , 624-627. https://doi.org/10.1021/acs.orglett.6b03779
- Ming Yan, Julian C. Lo, Jacob T. Edwards, and Phil S. Baran . Radicals: Reactive Intermediates with Translational Potential. Journal of the American Chemical Society 2016, 138 (39) , 12692-12714. https://doi.org/10.1021/jacs.6b08856
- Steven W. M. Crossley, Carla Obradors, Ruben M. Martinez, and Ryan A. Shenvi . Mn-, Fe-, and Co-Catalyzed Radical Hydrofunctionalizations of Olefins. Chemical Reviews 2016, 116 (15) , 8912-9000. https://doi.org/10.1021/acs.chemrev.6b00334
- Oliver Allemann, Manuela Brutsch, John C. Lukesh III, Daniel M. Brody, and Dale L. Boger . Synthesis of a Potent Vinblastine: Rationally Designed Added Benign Complexity. Journal of the American Chemical Society 2016, 138 (27) , 8376-8379. https://doi.org/10.1021/jacs.6b04330
- Lorenzo V. White and Martin G. Banwell . Conversion of the Enzymatically Derived (1S,2S)-3-Bromocyclohexa-3,5-diene-1,2-diol into Enantiomerically Pure Compounds Embodying the Pentacyclic Framework of Vindoline. The Journal of Organic Chemistry 2016, 81 (4) , 1617-1626. https://doi.org/10.1021/acs.joc.5b02788
- Justin E. Sears and Dale L. Boger . Tandem Intramolecular Diels–Alder/1,3-Dipolar Cycloaddition Cascade of 1,3,4-Oxadiazoles: Initial Scope and Applications. Accounts of Chemical Research 2016, 49 (2) , 241-251. https://doi.org/10.1021/acs.accounts.5b00510
- Justin E. Sears, Timothy J. Barker, and Dale L. Boger . Total Synthesis of (−)-Vindoline and (+)-4-epi-Vindoline Based on a 1,3,4-Oxadiazole Tandem Intramolecular [4 + 2]/[3 + 2] Cycloaddition Cascade Initiated by an Allene Dienophile. Organic Letters 2015, 17 (21) , 5460-5463. https://doi.org/10.1021/acs.orglett.5b02818
- Takahiro Morikawa, Shinji Harada, and Atsushi Nishida . Chiral Holmium Complex-Catalyzed Synthesis of Hydrocarbazole from Siloxyvinylindole and Its Application to the Enantioselective Total Synthesis of (−)-Minovincine. The Journal of Organic Chemistry 2015, 80 (17) , 8859-8867. https://doi.org/10.1021/acs.joc.5b01393
- Maxence Holtz, Carlos G Acevedo-Rocha, Michael K Jensen. Combining enzyme and metabolic engineering for microbial supply of therapeutic phytochemicals. Current Opinion in Biotechnology 2024, 87 , 103110. https://doi.org/10.1016/j.copbio.2024.103110
- Tian-Shu Wu, Yong-Jiu Hao, Zhong-Jian Cai, Shun-Jun Ji. Ligand-controlled regioselective cascade C–C/C–F cleavage/annulation of gem -DFCPs: a divergent synthesis of pyrroles. Organic Chemistry Frontiers 2024, 11 (4) , 1057-1061. https://doi.org/10.1039/D3QO01879B
- Jing Zhang, Quan‐Jian Luo, Han‐Chi Wang, Jin‐Heng Li, Bo Sun. Ru( II )‐Catalyzed ortho C—H Allylation of N ‐Aryl ‐7‐azaindoles with 2‐Methylidene Cyclic Carbonate. Chinese Journal of Chemistry 2024, 46 https://doi.org/10.1002/cjoc.202300627
- Rachel M. Gillard, Jiajun Zhang, Richard Steel, Jocelyn Wang, Jessica L. Strull, Bin Cai, Nilanjana Chakraborty, Dale L. Boger. Aryl Annulation: A Powerful Simplifying Retrosynthetic Disconnection. Synthesis 2024, 56 (01) , 118-133. https://doi.org/10.1055/a-1959-2088
- Rahul Shukla, Ajit Singh, Kamalinder K. Singh. Vincristine-based nanoformulations: a preclinical and clinical studies overview. Drug Delivery and Translational Research 2024, 14 (1) , 1-16. https://doi.org/10.1007/s13346-023-01389-6
- Shohreh Bakhshi, Alireza Shoari, Parisa Alibolandi, Mahmoud Ganji, Esraa Ghazy, Abbas Rahdar, Sonia Fathi-karkan, Sadanand Pandey. Emerging innovations in vincristine-encapsulated nanoparticles: Pioneering a new era in oncological therapeutics. Journal of Drug Delivery Science and Technology 2024, 91 , 105270. https://doi.org/10.1016/j.jddst.2023.105270
- P. K. Pournami, Nasheeda Rasheed, Athira Raveendran, Vipin Gopinath. Antineoplastic Drug Leads from Plants and Microbes. 2024, 287-331. https://doi.org/10.1007/978-981-99-9183-9_12
- Chong Qiu, Jun Zhe Zhang, Bo Wu, Cheng Chao Xu, Huan Huan Pang, Qing Chao Tu, Yu Qian Lu, Qiu Yan Guo, Fei Xia, Ji Gang Wang. Advanced application of nanotechnology in active constituents of Traditional Chinese Medicines. Journal of Nanobiotechnology 2023, 21 (1) https://doi.org/10.1186/s12951-023-02165-x
- Hong Zhang, Cui-Ping Li, Li-Li Wang, Zhuo-Da Zhou, Li Wen-Sen, Ling-Yi Kong, Yang Ming-Hua. Asperochones A and B, two antimicrobial aromatic polyketides from the endophytic fungus Aspergillus sp. MMC-2. Chinese Chemical Letters 2023, 82 , 109351. https://doi.org/10.1016/j.cclet.2023.109351
- Firdoos Ahmad Sofi, Nahida Tabassum. Natural product inspired leads in the discovery of anticancer agents: an update. Journal of Biomolecular Structure and Dynamics 2023, 41 (17) , 8605-8628. https://doi.org/10.1080/07391102.2022.2134212
- Ameer Fawad Zahoor, Sadaf Saeed, Azhar Rasul, Razia Noreen, Ali Irfan, Sajjad Ahmad, Shah Faisal, Sami A. Al-Hussain, Muhammad Athar Saeed, Muhammed Tilahun Muhammed, Zeinab A. Muhammad, Magdi E. A. Zaki. Synthesis, Cytotoxic, and Computational Screening of Some Novel Indole–1,2,4-Triazole-Based S-Alkylated N-Aryl Acetamides. Biomedicines 2023, 11 (11) , 3078. https://doi.org/10.3390/biomedicines11113078
- Anjali Gupta, Joydev K. Laha. Growing Utilization of Radical Chemistry in the Synthesis of Pharmaceuticals. The Chemical Record 2023, 23 (11) https://doi.org/10.1002/tcr.202300207
- Roland Wohlgemuth. Synthesis of Metabolites and Metabolite-like Compounds Using Biocatalytic Systems. Metabolites 2023, 13 (10) , 1097. https://doi.org/10.3390/metabo13101097
- Hui Xu, Yanfeng Dang. Unveiling the mechanism and origin of stereocontrol in dinuclear-zinc-catalyzed reductive desymmetrization of malonic esters. Organic Chemistry Frontiers 2023, 10 (18) , 4529-4541. https://doi.org/10.1039/D3QO00846K
- Ju Hee Kim, Sun A Lee, Tae Sik Jeon, Jin Kun Cha, Young Gyu Kim. A Unified Approach to Mono- and 2,3-Disubstituted N–H Indoles. Synlett 2023, 34 (14) , 1719-1722. https://doi.org/10.1055/s-0042-1752656
- Rishabha Malviya, Arun Kumar Singh, Deepika Yadav. Novel Strategies Preventing Emergence of MDR in Breast Cancer. 2023, 171-194. https://doi.org/10.1002/9781394209866.ch9
- Ramsha Munir, Ameer Fawad Zahoor, Sadia Javed, Bushra Parveen, Asim Mansha, Ahmad Irfan, Samreen Gul Khan, Ali Irfan, Katarzyna Kotwica-Mojzych, Mariusz Mojzych. Simmons–Smith Cyclopropanation: A Multifaceted Synthetic Protocol toward the Synthesis of Natural Products and Drugs: A Review. Molecules 2023, 28 (15) , 5651. https://doi.org/10.3390/molecules28155651
- Fuzhuo Li, Heping Deng, Hans Renata. Chemoenzymatic approaches for exploring structure–activity relationship studies of bioactive natural products. Nature Synthesis 2023, 2 (8) , 708-718. https://doi.org/10.1038/s44160-023-00358-8
- Kolawole Olofinsan, Heidi Abrahamse, Blassan P. George. Therapeutic Role of Alkaloids and Alkaloid Derivatives in Cancer Management. Molecules 2023, 28 (14) , 5578. https://doi.org/10.3390/molecules28145578
- Derek A. Leas, Daniel C. Schultz, Robert W. Huigens III. Chemical Reactions of Indole Alkaloids That Enable Rapid Access to New Scaffolds for Discovery. SynOpen 2023, 07 (02) , 165-185. https://doi.org/10.1055/a-2048-8412
- Shuai Jiang, Yu-Xin Huang, Xiao-Feng Wang, Xiao-Ping Xu, Shun-Jun Ji. Radical addition/spirocyclization cascade of tryptamine-derived isocyanides with aryl boronic acids: efficient access to spiroindoline derivatives. Organic Chemistry Frontiers 2023, 10 (7) , 1660-1668. https://doi.org/10.1039/D2QO01992B
- Xuefei Chen, Chao Huang, Kunlun Li, Junqiu Liu, Youyou Zheng, Yue Feng, Guo-yin Kai. Recent advances in biosynthesis and pharmacology of β-elemene. Phytochemistry Reviews 2023, 22 (1) , 169-186. https://doi.org/10.1007/s11101-022-09833-0
- Chhanda Charan Danta, Alakh Niranjan Sahu. Naturally occurring anticancer drugs. 2023, 539-588. https://doi.org/10.1016/B978-0-323-90575-6.00017-X
- Jun‐Xiong He, Xu‐Ge Si, Qi‐Tao Lu, Qian‐Wei Zhang, Quan Cai. An Enantioselective Approach to Heteroatom‐Containing Bicyclic Derivatives via Inverse‐Electron‐Demand Diels−Alder Reactions. Chinese Journal of Chemistry 2023, 41 (1) , 21-26. https://doi.org/10.1002/cjoc.202200441
- Mehdi Eshraghi, Mazaher Ahmadi, Saeid Afshar, Shahrokh Lorzadeh, Aida Adlimoghaddam, Nahid Rezvani Jalal, Ryan West, Sanaz Dastghaib, Somayeh Igder, Seyed Reza Naeimi Torshizi, Amir Mahmoodzadeh, Pooneh Mokarram, Tayyebeh Madrakian, Benedict C. Albensi, Marek J. Łos, Saeid Ghavami, Stevan Pecic. Enhancing autophagy in Alzheimer's disease through drug repositioning. Pharmacology & Therapeutics 2022, 237 , 108171. https://doi.org/10.1016/j.pharmthera.2022.108171
- Pei Dong, Zhaojing Li, Xiaohua Liu, Shunxi Dong, Xiaoming Feng. Asymmetric synthesis of polycyclic spiroindolines via the Dy-catalyzed cascade reaction of 3-(2-isocyanoethyl)indoles with aziridines. Organic Chemistry Frontiers 2022, 9 (17) , 4591-4597. https://doi.org/10.1039/D2QO00874B
- Liu‐Peng Zhao, Peng‐Juan Li, Lijia Wang, Yong Tang. Allenamide‐Initiated Cascade [2+2+2] Annulation Enabling the Divergent Total Synthesis of (−)‐Deoxoapodine, (−)‐Kopsifoline D and (±)‐Melotenine A. Angewandte Chemie International Edition 2022, 61 (34) https://doi.org/10.1002/anie.202207360
- Liu‐Peng Zhao, Peng‐Juan Li, Lijia Wang, Yong Tang. Allenamide‐Initiated Cascade [2+2+2] Annulation Enabling the Divergent Total Synthesis of (−)‐Deoxoapodine, (−)‐Kopsifoline D and (±)‐Melotenine A. Angewandte Chemie 2022, 134 (34) https://doi.org/10.1002/ange.202207360
- Gautier Bourbon, Ritchy Leroy, Carine Machado-Rodrigues, Georges Massiot. Catharanthine borane – An unexpected reaction product. Phytochemistry Letters 2022, 48 , 40-42. https://doi.org/10.1016/j.phytol.2022.01.009
- Dan Long, Gaoyuan Zhao, Zhiqiang Liu, Peiqi Chen, Shiqiang Ma, Xingang Xie, Xuegong She. Enantioselective Pictet–Spengler Condensation to Access the Total Synthesis of (+)‐Tabertinggine. European Journal of Organic Chemistry 2022, 2022 (10) https://doi.org/10.1002/ejoc.202200088
- Yan-Bo Zheng, Yan-Qun Dong, Shu-Yi Si, Yong-Su Zhen, Jian-Hua Gong. IMB5476, a novel microtubule inhibitor, induces mitotic catastrophe and overcomes multidrug resistance in tumors. European Journal of Pharmacology 2022, 919 , 174802. https://doi.org/10.1016/j.ejphar.2022.174802
- Xiao‐Tong Lin, Cheng Zhao, Da‐Ru Wang, Guang‐Cheng Wu, Guo‐Shu Chen, Shu‐Jie Chen, Hai Ren, Dong‐Sheng Deng, Yi‐Bing Xu, Xiao‐Wei Hu, Yun‐Lin Liu. BiCl 3 ‐Mediated Tandem Cyclization of Tryptamine‐Derived Ynamide: Concise Synthesis of Pentacyclic Spiroindolines and Tricyclic Indole Derivatives. Advanced Synthesis & Catalysis 2022, 364 (4) , 890-896. https://doi.org/10.1002/adsc.202101232
- Gen Li, Mingliang Lou, Xiangbing Qi. A brief overview of classical natural product drug synthesis and bioactivity. Organic Chemistry Frontiers 2022, 9 (2) , 517-571. https://doi.org/10.1039/D1QO01341F
- Jinfeng Kang, Todd R. Lewis, Alex Gardner, Rodrigo B. Andrade, Rongsheng E. Wang. Semi-syntheses and interrogation of indole-substituted Aspidosperma terpenoid alkaloids. Organic & Biomolecular Chemistry 2022, 177 https://doi.org/10.1039/D2OB00610C
- Xiangkai Kong, Yipeng Zhang, Lingjing Dang, Wen Chen, Hongbin Zhang. Research Progress in Synthesis of Indole Alkaloids Vindoline and Vindorosine. Chinese Journal of Organic Chemistry 2022, 42 (9) , 2728. https://doi.org/10.6023/cjoc202204009
- Jinghua Wu, Zhiqiang Ma. Metal-hydride hydrogen atom transfer (MHAT) reactions in natural product synthesis. Organic Chemistry Frontiers 2021, 8 (24) , 7050-7076. https://doi.org/10.1039/D1QO01139A
- Haizhen Li, Jinyu Wu, Jianfeng Zheng, Wei-Dong Z. Li. Synthesis of polycyclic spiroindolines via the cascade reaction of 3-(2-isocyanoethyl)indoles. Chemical Communications 2021, 57 (84) , 11092-11095. https://doi.org/10.1039/D1CC04576H
- Shi Tang, Shumin Ding, Dan Li, Lianjie Li, Haixia Zhao, Minxue Chai, Jian Wang. Palladium-catalysed imidoylative spirocyclization of 3-(2-isocyanoethyl)indoles. Chemical Communications 2021, 57 (81) , 10576-10579. https://doi.org/10.1039/D1CC03240B
- Fei Zhao, Jing Chen, Jin Qiao, Yangbin Lu, Xiaoning Zhang, Hui Mao, Shiyao Lu, Xin Gong, Siyu Liu, Xiaowei Wu, Long Dai. Chemo‐ and Regioselective Synthesis of Functionalized 1 H ‐imidazo[1,5‐ a ]indol‐3(2 H )‐ones via a Redox‐Neutral Rhodium(III)‐Catalyzed [4+1] Annulation between Indoles and Alkynes. Advanced Synthesis & Catalysis 2021, 363 (18) , 4380-4389. https://doi.org/10.1002/adsc.202100555
- Yulei Zhao, Shuai Li, Yuhang Fan, Xuqiang Guo, Xin Jiao, Laijin Tian, Xuejun Sun. Synthesis of 10 H ‐Indolo[1,2‐ a ]indole Derivatives via Intramolecular Cycloaddition and H‐Migration. European Journal of Organic Chemistry 2021, 2021 (30) , 4358-4363. https://doi.org/10.1002/ejoc.202100723
- Camillo La Mesa, Oliarinony Ranalison, Lovasoa N. Randriantseheno, Gianfranco Risuleo. Natural Products from Madagascar, Socio-Cultural Usage, and Potential Applications in Advanced Biomedicine: A Concise Review. Molecules 2021, 26 (15) , 4507. https://doi.org/10.3390/molecules26154507
- Matokah M. Abualnaja, Joseph Cowell, John D. Jolliffe, Corinne Wills, Paul G. Waddell, William Clegg, Michael J. Hall. Diastereoselective rearomative etherifications and aminations of 2,3,9,9a-tetrahydro-1H-carbazoles. Tetrahedron 2021, 89 , 132144. https://doi.org/10.1016/j.tet.2021.132144
- Byron A. Boon, Yi-Yun Yu, Dale L. Boger. Total synthesis of (−)-4-desacetoxy-1-oxovindoline: Single atom exchange of an embedded core heteroatom in vindoline. Tetrahedron 2021, 87 , 132117. https://doi.org/10.1016/j.tet.2021.132117
- The Hong Phong Nguyen, V. Bharath Kumar, Vinoth Kumar Ponnusamy, Thi Thu Thao Mai, Phuong Tran Nhat, Kathirvel Brindhadevi, Arivalagan Pugazhendhi. Phytochemicals intended for anticancer effects at preclinical levels to clinical practice: Assessment of formulations at nanoscale for non-small cell lung cancer (NSCLC) therapy. Process Biochemistry 2021, 104 , 55-75. https://doi.org/10.1016/j.procbio.2021.02.004
- Mallory Pullman, Francisco León, Stephen J. Cutler. Natural Products as Cytotoxic Agents. 2021, 1-89. https://doi.org/10.1002/0471266949.bmc216.pub2
- Sebastián J. Castro, José M. Padrón, Benjamin Darses, Viviana E. Nicotra, Philippe Dauban. Late‐stage Rh(II)‐catalyzed Nitrene Transfer for the Synthesis of Guaianolide Analogs with Enhanced Antiproliferative Activity. European Journal of Organic Chemistry 2021, 2021 (12) , 1859-1863. https://doi.org/10.1002/ejoc.202100074
- Jiawei Sun, He Yang, Wenjun Tang. Recent advances in total syntheses of complex dimeric natural products. Chemical Society Reviews 2021, 50 (4) , 2320-2336. https://doi.org/10.1039/D0CS00220H
- Pham T. Tham, Pham T. Chinh, Nguyen V. Tuyen, Duong N. Bang, Dinh T. Van, Vu T. Kien, Hoang T. Thanh, Duong H. Quynh, Vu D. Cuong, Nguyen H. Thanh, Alfonso Pérez-Encabo. Synthesis and cytotoxic evaluation of novel simplified plinabulin-quinoline derivatives. Mendeleev Communications 2021, 31 (2) , 213-215. https://doi.org/10.1016/j.mencom.2021.03.022
- Bruno Musquiari, Eduardo J. Crevelin, Bianca W. Bertoni, Suzelei de C. França, Ana Maria S. Pereira, Ana Carolina Devides Castello, Willian O. Castillo-Ordoñez, Silvana Giuliatti, Adriana A. Lopes. Precursor-directed Biosynthesis in Tabernaemontana catharinensis as a New Avenue for Alzheimerʼs Disease-modifying Agents. Planta Medica 2021, 87 (01/02) , 136-147. https://doi.org/10.1055/a-1315-2282
- Mahesh H. Shinde, Chepuri V. Ramana. An Apparent Umpolung Reactivity of Indole through [Au]‐Catalysed Cyclisation and Lewis‐Acid‐Mediated Allylation. Chemistry – A European Journal 2020, 26 (71) , 17171-17175. https://doi.org/10.1002/chem.202003441
- Zhi-Chen Wu, Dale L. Boger. The quest for supernatural products: the impact of total synthesis in complex natural products medicinal chemistry. Natural Product Reports 2020, 37 (11) , 1511-1531. https://doi.org/10.1039/D0NP00060D
- Fei Wang, Juan Li, Shengjie Fan, Zhigang Jin, Cheng Huang. Targeting stress granules: A novel therapeutic strategy for human diseases. Pharmacological Research 2020, 161 , 105143. https://doi.org/10.1016/j.phrs.2020.105143
- Samuel A. Bradley, Jie Zhang, Michael K. Jensen. Deploying Microbial Synthesis for Halogenating and Diversifying Medicinal Alkaloid Scaffolds. Frontiers in Bioengineering and Biotechnology 2020, 8 https://doi.org/10.3389/fbioe.2020.594126
- Lucie Cahlíková, Marcela Šafratová, Anna Hošťálková, Jakub Chlebek, Daniela Hulcová, Kateřina Breiterová, Lubomír Opletal. Pharmacognosy and Its Role in the System of Profile Disciplines in Pharmacy. Natural Product Communications 2020, 15 (9) , 1934578X2094545. https://doi.org/10.1177/1934578X20945450
- Xiaowei Wu, Pinyi Li, Yangbin Lu, Jin Qiao, Jingwei Zhao, Xiuwen Jia, Hangcheng Ni, Lichun Kong, Xiaoning Zhang, Fei Zhao. Rhodium‐Catalyzed Cascade Reactions of Indoles with 4‐Hydroxy‐2‐Alkynoates for the Synthesis of Indole‐Fused Polyheterocycles. Advanced Synthesis & Catalysis 2020, 362 (14) , 2953-2960. https://doi.org/10.1002/adsc.202000493
- Timothy Barker. Ferric Oxalate Hexahydrate. 2020, 1-4. https://doi.org/10.1002/047084289X.rn02346
- Guo‐Shu Chen, Shu‐Jie Chen, Jian Luo, Xiang‐Yu Mao, Albert Sun‐Chi Chan, Raymond Wai‐Yin Sun, Yun‐Lin Liu. Tandem Cross‐Coupling/Spirocyclization/Mannich‐Type Reactions of 3‐(2‐Isocyanoethyl)indoles with Diazo Compounds toward Polycyclic Spiroindolines. Angewandte Chemie 2020, 132 (2) , 624-631. https://doi.org/10.1002/ange.201911614
- Guo‐Shu Chen, Shu‐Jie Chen, Jian Luo, Xiang‐Yu Mao, Albert Sun‐Chi Chan, Raymond Wai‐Yin Sun, Yun‐Lin Liu. Tandem Cross‐Coupling/Spirocyclization/Mannich‐Type Reactions of 3‐(2‐Isocyanoethyl)indoles with Diazo Compounds toward Polycyclic Spiroindolines. Angewandte Chemie International Edition 2020, 59 (2) , 614-621. https://doi.org/10.1002/anie.201911614
- Junpei Matsuoka. Introduction. 2020, 1-18. https://doi.org/10.1007/978-981-15-8652-1_1
- Khoa Chung, Sarah E. O'Connor. Biosynthesis of Vinblastine. 2020, 642-685. https://doi.org/10.1016/B978-0-12-409547-2.14618-9
- M. Toufiqur Rahman, James M. Cook. The C-19 methyl substituted sarpagine-macroline-ajmaline alkaloids: Diversity, occurrence, bioactivity, and synthesis. 2020, 1-57. https://doi.org/10.1016/B978-0-12-817903-1.00001-2
- Adriana A. Lopes, Bianca Chioca, Bruno Musquiari, Eduardo J. Crevelin, Suzelei de C. França, Maria Fatima das G. Fernandes da Silva, Ana Maria S. Pereira. Unnatural spirocyclic oxindole alkaloids biosynthesis in Uncaria guianensis. Scientific Reports 2019, 9 (1) https://doi.org/10.1038/s41598-019-47706-3
- Ryan A. Shenvi, Jeishla L. M. Matos, Samantha A. Green. Hydrofunctionalization of Alkenes by Hydrogen‐Atom Transfer. 2019, 383-470. https://doi.org/10.1002/0471264180.or100.07
- Verrill M. Norwood, Robert W. Huigens. Harnessing the Chemistry of the Indole Heterocycle to Drive Discoveries in Biology and Medicine. ChemBioChem 2019, 20 (18) , 2273-2297. https://doi.org/10.1002/cbic.201800768
-
References
ARTICLE SECTIONS
This article references 50 other publications.
-
1Noble, R. L.; Beer, C. T.; Cutts, J. H. Role of chance observations in chemotherapy: Vinca rosea Ann. N.Y. Acad. Sci. 1958, 76, 882– 8941https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADyaG1M%252FlslCltQ%253D%253D&md5=a728fef90a06da248a734bfbed91a985Role of chance observations in chemotherapy: Vinca roseaNOBLE R L; BEER C T; CUTTS J HAnnals of the New York Academy of Sciences (1958), 76 (3), 882-94 ISSN:0077-8923.There is no expanded citation for this reference.
-
2Noble, R. L. Catharanthus roseus (vinca rosea): Importance and value of a chance observation Lloydia 1964, 27, 280– 281There is no corresponding record for this reference.
-
3Svoboda, G. H.; Nuess, N.; Gorman, M. Alkaloids of Vinca rosea Linn. (Catharanthus roseus G. Don.). V. Preparation and characterization of alkaloids J. Am. Pharm. Assoc. Sci. Ed. 1959, 48, 659– 6663https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaF3cXjsVeltw%253D%253D&md5=6946ca8bc3a4e61aac61d48861318ca4Alkaloids of Vinca rosea (Catharanthus roseus). V. Preparation and characterization of alkaloidsSvoboda, Gordon H.; Neuss, Norbert; Gorman, MarvinJournal of the American Pharmaceutical Association, Scientific Edition (1959), 48 (), 659-66CODEN: JAPMA8; ISSN:0095-9553.cf. preceding abstr. The following alkaloids were isolated from V. rosea [m.p., [α]26D (CHCl3), pK'a in 66% HCONMe2 and λ(EtOH) in mμ given]: vindoline, 154-5°, 42°, 5.5, 212, 250, 304; catharanthine, 126-8°, 29.8°, 6.8, 226, 284, 292; vindolinine-2HCl, 210-12° (decompn.), -8° (H2O), 3.3, 7.1,245,300; lochnericine, 190-3° (decompn.), -432°, 4.2, 226, 297, 327; leurosine (I), 202-5° (decompn.), 72°, 5.5, 7.5 (H2O), 214, 259; vincaleukoblastine (II), 211-16° (decompn.), 42° (detd. on the etherate), 5.4, 7.4 (H2O), 214,259; perivine, 180-1°, -121.4°, 7.5, 226,314; virosine, 258-64° (decompn.), -160.5°, 5.85, 226,270. I and II showed activity against P-1534 leukemia in mice.
-
4Neuss, N.; Neuss, M. N. Therapeutic use of bisindole alkaloids from catharanthus. In The Alkaloids; Brossi, A.; Suffness, M., Eds.; Academic: San Diego, CA, 1990; Vol. 37, pp 229– 240.There is no corresponding record for this reference.
-
5Pearce, H. L. Medicinal chemistry of bisindole alkaloids from Catharanthus. In The Alkaloids; Brossi, A.; Suffness, M., Eds.; Academic: San Diego, CA, 1990; Vol. 37, pp 145– 204.There is no corresponding record for this reference.
-
6Kuehne, M. E.; Marko, I. Syntheses of vinblastine-type alkaloids. In The Alkaloids; Brossi, A.; Suffness, M., Eds.; Academic: San Diego, CA, 1990; Vol. 37, pp 77– 132.There is no corresponding record for this reference.
-
7Fahy, J. Modifications in the “upper” velbenamine part of the Vinca alkaloids have major implications for tubulin interacting activities Curr. Pharm. Des. 2001, 7, 1181– 11977https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3MXmt1enu7s%253D&md5=91da38c20fa29bc51baf55eb6f76c388Modifications in the « upper » or velbenamine part of the Vinca alkaloids have major implications for tubulin interacting activitiesFahy, JacquesCurrent Pharmaceutical Design (2001), 7 (13), 1181-1197CODEN: CPDEFP; ISSN:1381-6128. (Bentham Science Publishers)A review with refs. Vinca alkaloids represent a chem. class of major interest in cancer chemotherapy. The lead compds. vinblastine and vincristine have been employed in clin. practice for more than thirty years and remain widely used to this day. Several hundred derivs. have been synthesized and evaluated for their pharmacol. activities, the majority being modified in the vindoline moiety, bearing several reactive centers. These efforts led to the identification of the amido deriv. vindesine, registered in Europe in 1980 and now available in several countries. Then novel chem. permitted the semisynthesis of derivs. modified in the velbenamine or « upper » part of the mol., creating a new potential in the Vinca alkaloids medicinal chem.: as a result, vinorelbine, obtained by C' ring contraction of anhydrovinblastine, and is now marketed worldwide. Several strategies aimed at the total synthesis of vinblastine derivs. have been investigated, giving the opportunity to design rationally certain compds. Modifications in the D' ring appeared to induce dramatic changes in the tubulin interactions. These observations have been confirmed recently by the identification of unprecedented pharmacol. properties exerted by the novel fluorinated Vinca alkaloid, vinflunine. This review will focus more specifically on derivs. which have been modified in the velbenamine part, with the aim of inducing different chem. and pharmacol. properties.
-
8Potier, P. Synthesis of the antitumor dimeric indole alkaloids from catharanthus species (vinblastine group) J. Nat. Prod. 1980, 43, 72– 868https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3cXhvFymuro%253D&md5=14aeb1a8af60a9996f94e4df1a6bdcd0Synthesis of the antitumor dimeric indole alkaloids from Catharanthus species (vinblastine group)Potier, PierreJournal of Natural Products (1980), 43 (1), 72-86CODEN: JNPRDF; ISSN:0163-3864.The synthesis of vinblastine alkaloids via a modified Polonovski reaction was reviewed with 49 refs. Norvinblastine alkaloids were also prepd. by this approach.
-
9Kutney, J. P. Plant cell culture combined with chemistry: a powerful route to complex natural products Acc. Chem. Res. 1993, 26, 559– 5669https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3sXmt1Cgtrg%253D&md5=ff8527ce783979c3d92af16b53bf6bf6Plant cell culture combined with chemistry: a powerful route to complex natural productsKutney, James P.Accounts of Chemical Research (1993), 26 (10), 559-66CODEN: ACHRE4; ISSN:0001-4842.Utilizing specific examples from the author's lab., a summary of the possible avenues of research in which plant cell culture methods combined with chem. can afford interesting routes to biol. active compds. is provided. The results presented illustrate the potential of such an interdisciplinary program and, in particular, reveal that various "shortcomings" in the utilization of plant cell cultures as sometimes expressed by various members of the scientific community (for example, cell line instability, long-term and low-level prodn. of metabolites, etc.) are invalid. With proper selection of methodol., gram-scale prodn. of end products, often in short-term expts. similar to those with microbial systems, can be achieved. The use of semicontinuous fermn. methods, for example, provides an approach of distinct interest in large-scale efficient prodn. of com. important products.
-
10Langlois, N.; Gueritte, F.; Langlois, Y.; Potier, P. Application of a modification of the Polonovski reaction to the synthesis of vinblastine-type alkaloids J. Am. Chem. Soc. 1976, 98, 7017– 702410https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE28XlvFaqt7s%253D&md5=14ccac703a16223a97e4d6952da6b12eApplication of a modification of the Polonovski reaction to the synthesis of vinblastine-type alkaloidsLanglois, Nicole; Gueritte, Francoise; Langlois, Yves; Potier, PierreJournal of the American Chemical Society (1976), 98 (22), 7017-24CODEN: JACSAT; ISSN:0002-7863.A new C-16-C-21 skeletal fragmentation of ibogane derivs., induced by the modified Polonovski reaction, lead in the presence of aspidospermane derivs. to vinblastine-type compds. with the natural C-16 configuration, such as vindoline and catharanthine N-oxide, which seems necessary for significant antitumor activity. This new method of coupling, which could be the same as the biogenetical pathway, was applied to partial synthesis of naturally occurring antitumor alkaloids of Catharanthus roseus. The circular dichroism distinguished between the natural or unnatural C-16' configurations. Another type of skeletal fragmentation at C-5-C-6, also encountered during this study, was minimized under the exptl. conditions.
-
11Kutney, J. P.; Hibino, T.; Jahngen, E.; Okutani, T.; Ratcliffe, A. H.; Treasurywala, A. M.; Wunderly, S. Total synthesis of indole and dihydroindole alkaloids. IX. Studies on the synthesis of bisindole alkaloids in the vinblastine-vincristine series. The biogenetic approach Helv. Chim. Acta 1976, 59, 2858– 288211https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaE2sXhtVKrt7k%253D&md5=a8f9948d39c38288220138df7d62c96eTotal synthesis of indole and dihydroindole alkaloids. IX. Studies on the synthesis of bisindole alkaloids in the vinblastine-vincristine series. The biogenetic approachKutney, James P.; Hibino, Toshihiko; Jahngen, Edwin; Okutani, Tetsuya; Ratcliffe, Arnold H.; Treasurywala, Adi M.; Wunderly, StephenHelvetica Chimica Acta (1976), 59 (8), 2858-83CODEN: HCACAV; ISSN:0018-019X.The reaction of catharanthine N-oxide and vindoline was carried out at various conditions. Under optimum conditions, which involve low temp. in (F3CCO)2O gave 3',4'-dehydrovinblastine I (R1 = R, R2 = CO2Me, R3 = H) as the exclusive product. I (R1 = CO2Me, R2 = R, R3 = H) and I (R1 = R, R2 = CO2Me, R3 = OH) were often isolated. The reaction, which follows the course of a Polonovski fragmentation process, was extended to the N-oxide derivs. of dihydrocatharanthine and decarbomethoxycatharanthine to give bisindole alkaloid derivs.
-
12Kuehne, M. E.; Matson, P. A.; Bornmann, W. G. Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20′-epi-vincovaline J. Org. Chem. 1991, 56, 513– 52812https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3MXhs1Cmu7k%253D&md5=dbdd7ea7d52b44b9814bc56ce6237925Enantioselective syntheses of vinblastine, leurosidine, vincovaline and 20'-epi-vincovalineKuehne, Martin E.; Matson, Patricia A.; Bornmann, William G.Journal of Organic Chemistry (1991), 56 (2), 513-28CODEN: JOCEAH; ISSN:0022-3263.The binary indole-indoline alkaloids vinblastine (I), leurosidine, 20'-epi-vincovaline, and vincovaline, were obtained by coupling of vindoline to the tetracyclic intermediates, e.g. II, followed by redn. and cyclization steps (60% overall yield for these reactions). The intermediates were obtained by enantioselective establishment of C20' through a first-step Sharpless oxidn. and followed by a subsequent diastereomeric sepn. Alternatively, enantioselective control of the key secodine-type cyclization in the reaction sequence provided the tetracyclic intermediates III for coupling to vindoline. Selective generation of the natural or unnatural atropisomeric forms of the alkaloids was achieved through alternative closures of ring D'. The natural products were also obtained from the higher energy atropisomers by conformational inversion on heating. For the vinblastine synthesis, the overall yield was 22%.
-
13Bornmann, W. G.; Kuehne, M. E. A common intermediate providing syntheses of ψ-tabersonine, coronaridine, iboxyphylline, ibophyllidine, vinamidine, and vinblastine J. Org. Chem. 1992, 57, 1752– 176013https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XhslCnu7k%253D&md5=47a9a9e4d4d55892f78c53fee45cb07bA common intermediate providing syntheses of Ψ-tabersonine, coronaridine, iboxyphylline, ibophyllidine, vinamidine, and vinblastineBornmann, William G.; Kuehne, Martin E.Journal of Organic Chemistry (1992), 57 (6), 1752-60CODEN: JOCEAH; ISSN:0022-3263.Generation of the key tetracyclic intermediates I in 6 steps (42% overall) and subsequent short redn., oxidn., and arylation sequences results in total syntheses of the tile compds., e.g. coronaridine II.
-
14Yokoshima, S.; Ueda, T.; Kobayashi, S.; Sato, A.; Kuboyama, T.; Tokuyama, H.; Fukuyama, T. Stereocontrolled total synthesis of (+)-vinblastine J. Am. Chem. Soc. 2002, 124, 2137– 213914https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38Xht1eltL8%253D&md5=c3f72b337748b01c2ab90b4ab6e6e12fStereocontrolled total synthesis of (+)-vinblastineYokoshima, Satoshi; Ueda, Toshihiro; Kobayashi, Satoshi; Sato, Ayato; Kuboyama, Takeshi; Tokuyama, Hidetoshi; Fukuyama, TohruJournal of the American Chemical Society (2002), 124 (10), 2137-2139CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A stereocontrolled total synthesis of (+)-vinblastine was accomplished, featuring prepns. of the two indole units (I and II) by means of a novel indole synthesis via radical cyclization of thioanilide, and a stereoselective coupling of these units.
Additionally, see:
Kuboyama, T.; Yokoshima, S.; Tokuyama, H.; Fukuyama, T. Stereocontrolled total synthesis of (+)-vincristine Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 11966– 1197014https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2cXntFeksr4%253D&md5=91eb430c84061368d23a89d1f5992f25Stereocontrolled total synthesis of (+)-vincristineKuboyama, Takeshi; Yokoshima, Satoshi; Tokuyama, Hidetoshi; Fukuyama, TohruProceedings of the National Academy of Sciences of the United States of America (2004), 101 (33), 11966-11970CODEN: PNASA6; ISSN:0027-8424. (National Academy of Sciences)An efficient total synthesis of (+)-vincristine has been accomplished through a stereoselective coupling of demethylvindoline and the eleven-membered carbomethoxyverbanamine precursor. Demethylvindoline was prepd. by oxidn. of 17-hydroxy-11-methoxytabersonine, followed by regioselective acetylation with mixed anhydride method. Although an initial attempt of coupling by using demethylvindoline formamide was not successful and resulted in recovery of the starting compds., the reaction using demethylvindoline took place smoothly to furnish the desired bisindole product with the correct stereochem. at C18'. After formation of the piperidine ring by sequential removal of the protective groups and intramol. nucleophilic cyclization, the total synthesis of vincristine was completed by formylation of N1. -
15Magnus, P.; Stamford, A.; Ladlow, M. Synthesis of the antitumor bisindole alkaloid vinblastine: diastereoselectivity and solvent effect on the stereochemistry of the crucial C-15-C-18′ bond J. Am. Chem. Soc. 1990, 112, 8210– 821215https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK3cXmtFans7o%253D&md5=75715cea7a43100a60b3287fb27b9df4Synthesis of the antitumor bisindole alkaloid vinblastine: diastereoselectivity and solvent effect on the stereochemistry of the crucial C-15-C-18' bondMagnus, Philip; Stamford, Andrew; Ladlow, MarkJournal of the American Chemical Society (1990), 112 (22), 8210-12CODEN: JACSAT; ISSN:0002-7863.Treatment of pyrrolocarboline I with ClCO2CH2C6H4NO2-p/vindoline/CH3NO2 at -20°C in the presence of 2,6-di-tert-butyl-4-methylpyridine gave the correct 18'(S) stereoisomer II (Q = CO2CH2C6H2NO2-4) which was converted in 3 steps to vinblastine. Of all of the various stereoisomers of I only one gave the correct C-18', C-2' and C-4' abs. stereochem.
-
16Ishikawa, H.; Colby, D. A.; Seto, S.; Va, P.; Tam, A.; Kakei, H.; Rayl, T. J.; Hwang, I.; Boger, D. L. Total synthesis of vinblastine, vincristine, related natural products, and key structural analogues J. Am. Chem. Soc. 2009, 131, 4904– 491616https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXjt1Gqtbw%253D&md5=da33d88f99ec7f3024a4efcf2198736eTotal Synthesis of Vinblastine, Vincristine, Related Natural Products, and Key Structural AnaloguesIshikawa, Hayato; Colby, David A.; Seto, Shigeki; Va, Porino; Tam, Annie; Kakei, Hiroyuki; Rayl, Thomas J.; Hwang, Inkyu; Boger, Dale L.Journal of the American Chemical Society (2009), 131 (13), 4904-4916CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Full details of the development of a direct coupling of catharanthine with vindoline to provide vinblastine (I) are described along with key mechanistic and labeling studies. Following an Fe(III)-promoted coupling reaction initiated by generation of a presumed catharanthine radical cation that undergoes a subsequent oxidative fragmentation and diastereoselective coupling with vindoline, addn. of the resulting reaction mixt. to an Fe(III)-NaBH4/air soln. leads to oxidn. of the C15'-C20' double bond and redn. of the intermediate iminium ion directly providing vinblastine (40-43%) and leurosidine (20-23%), its naturally occurring C20' alc. isomer. The yield of coupled products, which exclusively possess the natural C16' stereochem., approaches or exceeds 80% and the combined yield of the isomeric C20' alcs. is >60%. Preliminary studies of Fe(III)-NaBH4/air oxidn. reaction illustrate a generalizable trisubstituted olefin scope, identify alternatives to O2 trap at the oxidized carbon, provide a unique entry into C20' functionalized vinblastines, and afford initial insights into the obsd. C20' diastereoselectivity. The first disclosure of the use of exo-catharanthine proceeding through Δ19',20'-anhydrovinblastine in such coupling reactions is also detailed with identical stereochem. consequences. Incorporating either a catharanthine N-Me group or a vindoline N-formyl group precludes Fe(III)-promoted coupling, whereas the removal of the potentially key C16 methoxy group of vindoline does not adversely impact the coupling efficiency. Extension of these studies provided a total synthesis of vincristine (II) via N-desmethylvinblastine (also a natural product), 16-desmethoxyvinblastine and 4-desacetoxy-16-desmethoxyvinblastine both of which we can now suggest are likely natural products produced by C. roseus, desacetylvinblastine and 4-desacetoxyvinblastine, as well as a series of key analogs bearing systematic modifications in the vindoline subunit. Their biol. evaluation provided addnl. insights into the key functionality within the vindoline subunit contributing to the activity and sets the foundation on which further, more deep-seated changes in the structures of I and II will be explored in future studies.
-
17Ishikawa, H.; Elliott, G. I.; Velcicky, J.; Choi, Y.; Boger, D. L. Total synthesis of (−)- and ent-(+)-vindoline and related alkaloids J. Am. Chem. Soc. 2006, 128, 10596– 1061217https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xnt12nsLs%253D&md5=38749a412611ea9892da0a1453deff73Total Synthesis of (-)- and ent-(+)-Vindoline and Related AlkaloidsIshikawa, Hayato; Elliott, Gregory I.; Velcicky, Juraj; Choi, Younggi; Boger, Dale L.Journal of the American Chemical Society (2006), 128 (32), 10596-10612CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A concise 11-step total synthesis of (-)- and ent-(+)-vindoline is detailed based on a unique tandem intramol. [4 + 2]/[3 + 2] cycloaddn. cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which three rings and four C-C bonds are formed central to the characteristic pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. As key elements of the scope and stereochem. features of the reaction were defined, a series of related natural products of increasing complexity were prepd. by total synthesis including both enantiomers of minovine, 4-desacetoxy-6,7-dihydrovindorosine, 4-desacetoxyvindorosine, and vindorosine as well as N-methylaspidospermidine. Subsequent extensions of the approach provided both enantiomers of 6,7-dihydrovindoline, 4-desacetoxyvindoline, and 4-desacetoxy-6,7-dihydrovindoline.
-
18Choi, Y.; Ishikawa, H.; Velcicky, J.; Elliott, G. I.; Miller, M. M.; Boger, D. L. Total synthesis of (−)- and ent-(+)-vindoline Org. Lett. 2005, 7, 4539– 454218https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXpt1Whu74%253D&md5=66153575bab3f154b43c9e5f56b01752Total Synthesis of (-)- and ent-(+)-VindolineChoi, Younggi; Ishikawa, Hayato; Velcicky, Juraj; Elliott, Gregory I.; Miller, Michael M.; Boger, Dale L.Organic Letters (2005), 7 (20), 4539-4542CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)Two exceptionally concise total syntheses of (-)-vindoline (I) and ent-(+)-vindoline are detailed enlisting a diastereoselective tandem [4+2]/[3+2] cycloaddn. of a 1,3,4-oxadiazole. The unique reaction cascade assembles the fully functionalized pentacyclic ring system of vindoline in a single step that forms four C-C bonds and three rings while introducing all requisite functionality and setting all six stereocenters within the central ring including three contiguous and four total quaternary centers.
-
19Yuan, Z.; Ishikawa, H.; Boger, D. L. Total synthesis of natural (−)- and ent-(+)-4-desacetoxy-6,7-dihydrovindorosine and natural and ent-minovine: oxadiazole tandem intramolecular Diels–Alder/1,3-dipolar cycloaddition reaction Org. Lett. 2005, 7, 741– 74419https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXmslSmuw%253D%253D&md5=2064655c266ccd452f11a22e3a754486Total synthesis of natural (+)- and ent-(-)-4-desacetoxy-6,7-dihydrovindorosine and natural and ent-minovine: oxadiazole tandem intramolecular Diels-Alder/1,3-dipolar cycloaddition reactionYuan, Zhong Qing; Ishikawa, Hayato; Boger, Dale L.Organic Letters (2005), 7 (4), 741-744CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)Efficient and unusually concise total syntheses of both enantiomers of the Aspidosperma alkaloids 4-desacetoxy-6,7-dihydrovindorosine (I) and minovine (II) are detailed. A tandem intramol. Diels-Alder/1,3-dipolar cycloaddn. reaction of the 1,3,4-oxadiazole III, in which three new rings, four new C-C bonds, and five stereocenters are formed, is a key step in the sequence. The availability of optically active material permitted an assessment of the enantiomeric integrity of minovine and the source of its reported unusual optical rotation.
-
20Elliott, G. I.; Velcicky, J.; Ishikawa, H.; Li, Y.; Boger, D. L. Total synthesis of (−)- and ent-(+)-vindorosine: tandem intramolecular Diels–Alder/1,3-dipolar cycloaddition reaction of 1,3,4-oxadiazoles Angew. Chem., Int. Ed. 2006, 45, 620– 622There is no corresponding record for this reference.
-
21Ishikawa, H.; Boger, D. L. Total synthesis of natural (−)- and ent-(+)-4-desacetoxy-5-desethylvindoline Heterocycles 2007, 72, 95– 102There is no corresponding record for this reference.
-
22Elliott, G. I.; Fuchs, J. R.; Blagg, B. S. J.; Ishikawa, H.; Tao, H.; Yuan, Z.; Boger, D. L. Intramolecular Diels–Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles J. Am. Chem. Soc. 2006, 128, 10589– 1059522https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD28Xnt12nsLo%253D&md5=754e07e1bcdabfbef4ba4dc5a15911deIntramolecular Diels-Alder/1,3-Dipolar Cycloaddition Cascade of 1,3,4-OxadiazolesElliott, Gregory I.; Fuchs, James R.; Blagg, Brian S. J.; Ishikawa, Hayato; Tao, Houchao; Yuan, Z.-Q.; Boger, Dale L.Journal of the American Chemical Society (2006), 128 (32), 10589-10595CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)The intramol. [4 + 2]/[3 + 2] cascade intramol. cycloaddn. of 1,3,4-oxadiazoles, e.g. I (R = H, Me, Me3CSiMe2OCH2, Ph, PhCH2O, CN, MeO2C), to afford polyheterocycles, e.g. II, has been systematically explored and the scope and utility of the reaction have been defined.
-
23Wilkie, G. D.; Elliott, G. I.; Blagg, B. S. J.; Wolkenberg, S. E.; Soenen, D. B.; Miller, M. M.; Pollack, S.; Boger, D. L. Intramolecular Diels–Alder and tandem intramolecular Diels–Alder/1,3-dipolar cycloaddition reactions of 1,3,4-oxadiazoles J. Am. Chem. Soc. 2002, 124, 11292– 1129423https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD38XmsFGmu70%253D&md5=413092b5f48d5b5fa3d2bc39baa715feIntramolecular Diels-Alder and Tandem Intramolecular Diels-Alder/1,3-Dipolar Cycloaddition Reactions of 1,3,4-OxadiazolesWilkie, Gordon D.; Elliott, Gregory I.; Blagg, Brian S. J.; Wolkenberg, Scott E.; Soenen, Danielle R.; Miller, Michael M.; Pollack, Scott; Boger, Dale L.Journal of the American Chemical Society (2002), 124 (38), 11292-11294CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Polycycles such as I and II are prepd. by stereoselective intramol. Diels-Alder reactions of indole- and alkene-contg. oxadiazoles such as III and IV followed by loss of nitrogen and stereoselective intramol. [3+2] dipolar cycloaddn. The reactants are prepd. in short sequences from alkene- or indole-contg. carboxylic acids and aminooxadiazoles prepd. by cyclocondensation of oxalylsemicarbazides. Heating in either 1,2-dichlorobenzene at 180° or in 1,3,5-triisopropylbenzene at 230° gives the polycyclic products in 41-87% yields. The geometry of the products is detd. by the alkene geometry and by stereoselective addn. of the indole to the α-face of the intermediate oxonium ylide; this allows up to six stereocenters to be set reliably in a single reaction. Only oxadiazoles undergo stereoselective cycloaddn. reactions; neither thiadiazoles or N-methyltriazoles react at all. One of the substituents on the oxadiazolylamine must be an acyl group for cycloaddn. to occur. Alkynyl-substituted oxadiazoles also undergo cycloaddn. reactions to give fused furans; alkyne equiv. are also effective, such as in the prepn. of V by tandem cycloaddn. and elimination reactions of VI. This reaction sequence provides rapid access to the ring system and substitution pattern of vindoline.
-
24Boger, D. L. Diels–Alder reactions of azadienes Tetrahedron 1983, 39, 2869– 293924https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL2cXjsVChug%253D%253D&md5=c577e1f3bdeb12a2cdcc17c3a25d0bd3Diels-Alder reactions of azadienesBoger, Dale L.Tetrahedron (1983), 39 (18), 2869-939CODEN: TETRAB; ISSN:0040-4020.A review with 203 refs.
-
25Boger, D. L. Diels–Alder reactions of heterocyclic azadienes Chem. Rev. 1986, 86, 781– 793There is no corresponding record for this reference.
-
26Vukovic, J.; Goodbody, A. E.; Kutney, J. P.; Misawa, M. Production of 3′,4′-anhydrovinblastine: a unique chemical synthesis Tetrahedron 1988, 44, 325– 33126https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL1cXkvFensrs%253D&md5=99df6516eb456055d2095d25f3a1d580Production of 3',4'-anhydrovinblastine: a unique chemical synthesisVukovic, J.; Goodbody, A. E.; Kutney, J. P.; Misawa, M.Tetrahedron (1988), 44 (2), 325-31CODEN: TETRAB; ISSN:0040-4020.Preliminary investigations have led to the discovery that ferric ion can couple catharanthine and vindoline in aq. acidic media to produce 3',4'-anhydrovinblastine as the major product. A conversion of 77% could be realized under optimized conditions.
-
27Ishikawa, H.; Colby, D. A.; Boger, D. L. Direct coupling of catharanthine and vindoline to provide vinblastine: total synthesis of (+)- and ent-(−)-vinblastine J. Am. Chem. Soc. 2008, 130, 420– 42127https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhsVehu7%252FK&md5=f06c9711d4ccb2dc4c45bf79120126feDirect Coupling of Catharanthine and Vindoline to Provide Vinblastine: Total Synthesis of (+)- and ent-(-)-VinblastineIshikawa, Hayato; Colby, David A.; Boger, Dale L.Journal of the American Chemical Society (2008), 130 (2), 420-421CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A direct coupling of catharanthine I with vindoline II to provide vinblastine III is detailed along with key mechanistic and labeling studies. Following an Fe(III)-promoted coupling reaction initiated by generation of a presumed catharanthine amine radical cation that undergoes a subsequent oxidative fragmentation and diastereoselective coupling with vindoline, addn. of the resulting reaction mixt. to an Fe(III)-NaBH4/air soln. leads to oxidn. of the C15'-C21' double bond and redn. of the intermediate iminium ion directly providing vinblastine (43%) and leurosidine (23%), its naturally occurring C21' alc. isomer. The yield of coupled products, which exclusively possess the natural C16' stereochem., approaches or exceeds 80%, and the combined yield of the isomeric C21' alcs. is 66%.
-
28Sasaki, Y.; Kato, D.; Boger, D. L. Asymmetric total synthesis of vindorosine, vindoline, and key vinblastine analogues J. Am. Chem. Soc. 2010, 132, 13533– 1354428https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtV2kur3M&md5=1238182ac0bd1cf56d5354492d316014Asymmetric Total Synthesis of Vindorosine, Vindoline, and Key Vinblastine AnaloguesSasaki, Yoshikazu; Kato, Daisuke; Boger, Dale L.Journal of the American Chemical Society (2010), 132 (38), 13533-13544CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Vindoline I (R = MeO) and vindorosine I (R = H) are prepd. stereoselectively using the tandem intramol. [4 + 2]/[3 + 2] cycloaddn. cascades of indole-substituted 1,3,4-oxadiazoleamides such as II (R1 = H, PhCH2O; R2 = PhCH2O, H; MOM = methoxymethyl) to give hexacycles such as III (R1 = H, PhCH2O; R2 = PhCH2O, H) as the key steps. II (R1 = H, PhCH2O; R2 = PhCH2O, H) are prepd. in six or nine steps from protected D-serine and D-aspartic acid moieties, resp.; the methoxymethoxymethyl moiety controls the facial selectivity of the initiating Diels-Alder reactions of II and sets the abs. stereochem. of the remaining six stereocenters in the cascade cycloadducts. A ring expansion reaction is developed to generate the 6-membered ring with appropriate functionality for introduction of the Δ6,7-double bond found in I. I (R = MeO) and related analogs generated in its synthesis are converted to vinblastine analogs by iron-mediated oxidative coupling reactions with catharanthine sulfate; the activities of the vinblastine analogs against murine leukemia and drug-susceptible and drug-resistant human colon cancer cell lines are detd. Analogs of vinblastine lacking the vinblastine Δ6,7-double bond inhibit cancer cells only at concns. 100-fold greater than that at which vinblastine inhibits the same cancer cells. The structures of selected intermediates in the prepn. of I (R = H, MeO) or of their enantiomers are detd. by X-ray crystallog.
-
29Kato, D.; Sasaki, Y.; Boger, D. L. Asymmetric total synthesis of vindoline J. Am. Chem. Soc. 2010, 132, 3685– 368729https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXisVOqsrs%253D&md5=26f4d78eb3595ec77264863543c33c5cAsymmetric Total Synthesis of VindolineKato, Daisuke; Sasaki, Yoshikazu; Boger, Dale L.Journal of the American Chemical Society (2010), 132 (11), 3685-3687CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A concise asym. total synthesis of (-)-vindoline (I) is detailed based on a tandem intramol. [4+2]/[3+2] cycloaddn. cascade of a 1,3,4-oxadiazole II inspired by the natural product structure, in which the tether linking the initiating dienophile and oxadiazole bears a chiral substituent that controls the facial selectivity of the initiating Diels-Alder reaction and sets abs. stereochem. of the remaining six stereocenters in the cascade cycloadduct. This key reaction introduces three rings and four C-C bonds central to the pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. Implementation of the approach also required the development of a unique ring expansion reaction to provide a six-membered ring suitably functionalized for introduction of the Δ-double bond found in the core structure of vindoline and defined our use of a protected hydroxymethyl group as the substituent used to control the stereochem. course of the cycloaddn. cascade.
-
30Kuehne, M. E.; Bornmann, W. G.; Marko, I.; Qin, Y.; Le Boulluec, K. L.; Frasier, D. A.; Xu, F.; Malamba, T.; Ensinger, C. L.; Borman, L. S.; Huot, A. E.; Exon, C.; Bizzarro, F. T.; Cheung, J. B.; Bane, S. L. Syntheses and biological evaluation of vinblastine congeners Org. Biomol. Chem. 2003, 1, 2120– 2136There is no corresponding record for this reference.
-
31Miyazaki, T.; Yokoshima, S.; Simizu, S.; Osada, H.; Tokuyama, H.; Fukuyama, T. Synthesis of (+)-vinblastine and its analogues Org. Lett. 2007, 9, 4737– 474031https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtFKhtbbN&md5=69b307f1a999da3091938428fbc98072Synthesis of (+)-Vinblastine and Its AnaloguesMiyazaki, Tohru; Yokoshima, Satoshi; Simizu, Siro; Osada, Hiroyuki; Tokuyama, Hidetoshi; Fukuyama, TohruOrganic Letters (2007), 9 (23), 4737-4740CODEN: ORLEF7; ISSN:1523-7060. (American Chemical Society)A synthetic route to vinblastine and its analogs with an ethynyl group, which features a stereoselective coupling of an 11-membered key intermediate with vindoline, is described. Transformations of the alkynyl moiety including a partial redn. as well as a Sonogashira coupling furnished a variety of analogs.
-
32Voss, M. E.; Ralph, J. M.; Xie, D.; Manning, D. D.; Chen, X.; Frank, A. J.; Leyhane, A. J.; Liu, L.; Stevens, J. M.; Budde, C.; Surman, M. D.; Friedrich, T.; Peace, D.; Scott, I. L.; Wolf, M.; Johnson, R. Synthesis and SAR of vinca alkaloid analogues Bioorg. Med. Chem. Lett. 2009, 19, 1245– 124932https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXit1Wru74%253D&md5=5e1b81b6ea85a9fbfc10f2f8cca61ce4Synthesis and SAR of Vinca alkaloid analogsVoss, Matthew E.; Ralph, Jeffery M.; Xie, Dejian; Manning, David D.; Chen, Xinchao; Frank, Anthony J.; Leyhane, Andrew J.; Liu, Lei; Stevens, Jason M.; Budde, Cheryl; Surman, Matthew D.; Friedrich, Thomas; Peace, Denise; Scott, Ian L.; Wolf, Mark; Johnson, RandallBioorganic & Medicinal Chemistry Letters (2009), 19 (4), 1245-1249CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)Versatile intermediates 12'-iodovinblastine, 12'-iodovincristine and 11'-iodovinorelbine I [R1 = Me, R3' = H, R4' = OH-β, R12' = iodo, X7' = (CH2)2; R1 = CHO, R3' = H, R4' = OH-β, R12' = iodo, X7' = (CH2)2; R1 = Me, R3'R4' = bond, R12' = iodo, X7' = CH2, resp.] were utilized as substrates for transition metal based chem. which led to the prepn. of novel analogs of the Vinca alkaloids. The synthesis of key iodo intermediates, their transformation into final products and the SAR based upon HeLa and MCF-7 cell toxicity assays was presented. Selected analogs I [R1 = Me, R3' = H, R4' = OH-β, R12' = Me, SMe, X7' = (CH2)2] showed promising anticancer activity in the P388 murine leukemia model.
-
33Gherbovet, O.; Coderch, C.; Alvarez, M. C. G.; Bignon, J.; Thoret, S.; Martin, M.-T.; Guéritte, F.; Gago, F.; Roussi, F. Synthesis and biological evaluation of a new series of highly functionalized 7′-homo-anhydrovinblastine derivatives J. Med. Chem. 2013, 56, 6088– 6100There is no corresponding record for this reference.
-
34Va, P.; Campbell, E. L.; Robertson, W. M.; Boger, D. L. Total synthesis and evaluation of a key series of C5-substituted vinblastine derivatives J. Am. Chem. Soc. 2010, 132, 8489– 849534https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXmvFarsrY%253D&md5=32a2dee454ee115192b93fa7764a44afTotal Synthesis and Evaluation of a Key Series of C5-Substituted Vinblastine DerivativesVa, Porino; Campbell, Erica L.; Robertson, William M.; Boger, Dale L.Journal of the American Chemical Society (2010), 132 (24), 8489-8495CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Desacetoxyvinblastine derivs. such as I [R = H, Me, Et, EtCH2, HC≡C, H2C:CH, HOCH2, OHC, (S)-R1OCCH2CH(OR1), Me3CMe2SiC≡C; R1 = H, EtCH2CO] (vinblastine analogs) with varying C5 substituents are prepd. stereoselectively using the intramol. domino [4+2]/[3+2] cycloaddn. reactions of (alkenoyl)(indoleethyl)amino oxazadiazolecarboxylates II (R = H, Me, EtCH2, HC≡C) to form the vindoline analogs III (R = H, Me, EtCH2, HC≡C) and the stereoselective biomimetic oxidative coupling reactions of vindoline analogs with catharanthine sulfate as the key steps. The antitumor activities of I [R = H, Me, Et, EtCH2, HC≡C, H2C:CH, HOCH2, OHC, (S)-R1OCCH2CH(OR1), Me3CMe2SiC≡C; R1 = H, EtCH2CO], epimeric leurosidine and anhydrovinblastine analogs generated in the oxidative coupling step with catharanthine sulfate, and lactone and dehydrovindoline-contg. analogs are detd. in human cell lines. The tubulin binding site surrounding the C5 substituent of vinblastine analogs is exquisitely sensitive to the presence, shape, and polarity of the substituent; only the vinblastine analog I (R = Me) has anticancer activity approaching that obsd. with the vinblastine analog I (R = Et) with the Et group present in vinblastine.
-
35Schleicher, K. D.; Sasaki, Y.; Tam, A.; Kato, D.; Duncan, K. K.; Boger, D. L. Total synthesis and evaluation of vinblastine analogues containing systematic deep-seated modifications in the vindoline subunit ring system: core redesign J. Med. Chem. 2013, 56, 483– 49535https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvVKhurrO&md5=1a7addebed643550c8828ef70c155480Total Synthesis and Evaluation of Vinblastine Analogues Containing Systematic Deep-Seated Modifications in the Vindoline Subunit Ring System: Core RedesignSchleicher, Kristin D.; Sasaki, Yoshikazu; Tam, Annie; Kato, Daisuke; Duncan, Katharine K.; Boger, Dale L.Journal of Medicinal Chemistry (2013), 56 (2), 483-495CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)The total synthesis of a systematic series of vinblastine analogs that contain deep-seated structural modifications to the core ring system of the lower vindoline subunit is described. Complementary to the vindoline 6,5 DE ring system, compds. with 5,5, 6,6, and the reversed 5,6 membered DE ring systems were prepd. Both the natural cis and unnatural trans 6,6-membered ring systems proved accessible, with the latter representing a surprisingly effective class for analog design. Following Fe(III)-promoted coupling with catharanthine and in situ oxidn. to provide the corresponding vinblastine analogs, their evaluation provided unanticipated insights into how the structure of the vindoline subunit contributes to activity. Two potent analogs (I and II) possessing two different unprecedented modifications to the vindoline subunit core architecture were discovered that matched the potency of the comparison natural products and both lack the 6,7-double bond whose removal in vinblastine leads to a 100-fold drop in activity.
-
36Leggans, E. K.; Barker, T. J.; Duncan, K. K.; Boger, D. L. Iron(III)/NaBH4-mediated additions to unactivated alkenes: synthesis of novel 20′-vinblastine analogues Org. Lett. 2012, 14, 1428– 143136https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XivVOnsrg%253D&md5=954aa67e2b5d5b7f9ce2ac8b02c8857aIron(III)/NaBH4-Mediated Additions to Unactivated Alkenes: Synthesis of Novel 20'-Vinblastine AnaloguesLeggans, Erick K.; Barker, Timothy J.; Duncan, Katharine K.; Boger, Dale L.Organic Letters (2012), 14 (6), 1428-1431CODEN: ORLEF7; ISSN:1523-7052. (American Chemical Society)An Fe(III)/NaBH4-mediated reaction for the functionalization of unactivated alkenes is described defining the alkene substrate scope, establishing the exclusive Markovnikov addn., exploring a range of free radical traps, examg. the Fe(III) salt and initiating hydride source, introducing H2O-cosolvent mixts., and exploring catalytic variants. Its use led to the prepn. of a novel, potent, and previously inaccessible C20'-vinblastine analog, I [X = NHCONHCOCCl3, NHCONH2, NHCSNH2].
-
37Leggans, E. K.; Duncan, K. K.; Barker, T. J.; Schleicher, K. D.; Boger, D. L. A remarkable series of vinblastine analogues displaying enhanced activity and an unprecedented tubulin binding steric tolerance: C20′ urea derivatives J. Med. Chem. 2013, 56, 628– 63937https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhvVCqs7fJ&md5=3af29fd43a2de5b0d6bcc7f79f5ce280A Remarkable Series of Vinblastine Analogues Displaying Enhanced Activity and an Unprecedented Tubulin Binding Steric Tolerance: C20' Urea DerivativesLeggans, Erick K.; Duncan, Katharine K.; Barker, Timothy J.; Schleicher, Kristin D.; Boger, Dale L.Journal of Medicinal Chemistry (2013), 56 (3), 628-639CODEN: JMCMAR; ISSN:0022-2623. (American Chemical Society)A systematic series of previously inaccessible key C20' urea and thiourea derivs. of vinblastine were prepd. from 20'-aminovinblastine that was made accessible through a unique Fe(III)/NaBH4-mediated alkene functionalization reaction of anhydrovinblastine. Their examn. defined key structural features of the urea-based analogs that contribute to their properties and provided derivs. that match or exceed the potency of vinblastine by as much as 10-fold in cell-based functional assays, which is directly related to their relative tubulin binding affinity. In contrast to expectations based on apparent steric constraints of the tubulin binding site surrounding the vinblastine C20' center depicted in an X-ray cocrystal structure, remarkably large C20' urea derivs. are accommodated.
-
38Barker, T. J.; Duncan, K. K.; Otrubova, K.; Boger, D. L. Potent vinblastine C20′ ureas displaying additionally improved activity against a vinblastine-resistant cancer cell line ACS Med. Chem. Lett. 2013, 4, 985– 988There is no corresponding record for this reference.
-
39Tam, A.; Gotoh, H.; Robertson, W. M.; Boger, D. L. Catharanthine C16 substituent effects on the biomimetic coupling with vindoline: preparation and evaluation of a key series of vinblastine analogues Bioorg. Med. Chem. Lett. 2010, 20, 6408– 641039https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXhtlSms7jI&md5=11d7a0b077fac4cfbdf58d862a885d90Catharanthine C16 substituent effects on the biomimetic coupling with vindoline: Preparation and evaluation of a key series of vinblastine analoguesTam, Annie; Gotoh, Hiroaki; Robertson, William M.; Boger, Dale L.Bioorganic & Medicinal Chemistry Letters (2010), 20 (22), 6408-6410CODEN: BMCLE8; ISSN:0960-894X. (Elsevier B.V.)The examn. of the catharanthine C16 substituent effects on the Fe(III)-promoted biomimetic coupling reaction with vindoline is detailed, confirming the importance of the presence of a C16 electron-withdrawing substituent, and establishing an unanticipated unique role (>10-fold) that the C16 Me ester plays in the expression of the natural product properties. Thus, replacement of the vinblastine C16' Me ester with an Et ester (10-fold), a cyano group (100-fold), an aldehyde (100-fold), a hydroxymethyl group (1000-fold) or a primary carboxamide (>1000-fold) led to surprisingly large redns. in cytotoxic activity.
-
40Gotoh, H.; Duncan, K. K.; Robertson, W. M.; Boger, D. L. 10′-Fluorovinblastine and 10′-fluorovincristine: synthesis of a key series of modified Vinca alkaloids ACS Med. Chem. Lett. 2011, 2, 948– 952There is no corresponding record for this reference.
-
41Gotoh, H.; Sears, J. E.; Eschenmoser, A.; Boger, D. L. New insights into the mechanism and an expanded scope of the Fe(III)-mediated vinblastine coupling reaction J. Am. Chem. Soc. 2012, 134, 13240– 1324341https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFChtL7E&md5=375df8d7c8c4e1ed4d3ee15f7fee371dNew Insights into the Mechanism and an Expanded Scope of the Fe(III)-Mediated Vinblastine Coupling ReactionGotoh, Hiroaki; Sears, Justin E.; Eschenmoser, Albert; Boger, Dale L.Journal of the American Chemical Society (2012), 134 (32), 13240-13243CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A definition of the scope of arom. substrates that participate with catharanthine in an Fe(III)-mediated coupling reaction, an examn. of the key structural features of catharanthine required for participation in the reaction, and the development of a generalized indole functionalization reaction that bears little structural relationship to catharanthine itself are detailed. In addn. to providing insights into the mechanism of the Fe(III)-mediated coupling reaction of catharanthine with vindoline suggesting the reaction conducted in acidic aq. buffer may be radical mediated, the studies provide new opportunities for the prepn. of previously inaccessible vinblastine analogs and define powerful new methodol. for the synthesis of indole-contg. natural and unnatural products.
-
42
We thank Gregory Vite and Robert Borzilleri for arranging and overseeing this assessment and Craig Fairchild, Kathy Johnson, and Russell Peterson for conducting the testing at Bristol–Myers Squibb.
There is no corresponding record for this reference. -
43Gigant, B.; Wang, C.; Ravelli, R. B. G.; Roussi, F.; Steinmetz, M. O.; Curmi, P. A.; Sobel, A.; Knossow, M. Structural basis for the regulation of tublin by vinblastine Nature 2005, 435, 519– 52243https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXksVeisrc%253D&md5=25451d6a11a9626c4baa02890b16f6aeStructural basis for the regulation of tubulin by vinblastineGigant, Benoit; Wang, Chunguang; Ravelli, Raimond B. G.; Roussi, Fanny; Steinmetz, Michel O.; Curmi, Patrick A.; Sobel, Andre; Knossow, MarcelNature (London, United Kingdom) (2005), 435 (7041), 519-522CODEN: NATUAS; ISSN:0028-0836. (Nature Publishing Group)Vinblastine is one of several tubulin-targeting Vinca alkaloids that have been responsible for many chemotherapeutic successes since their introduction in the clinic as antitumor drugs. In contrast with the two other classes of small tubulin-binding mols. (Taxol and colchicine), the binding site of vinblastine is largely unknown and the mol. mechanism of this drug has remained elusive. Here we report the x-ray structure of vinblastine bound to tubulin in a complex with the RB3 protein stathmin-like domain (RB3-SLD). Vinblastine introduces a wedge at the interface of two tubulin mols. and thus interferes with tubulin assembly. Together with electron microscopical and biochem. data, the structure explains vinblastine-induced tubulin self-assocn. into spiral aggregates at the expense of microtubule growth. It also shows that vinblastine and the amino-terminal part of RB3-SLD binding sites share a hydrophobic groove on the α-tubulin surface that is located at an intermol. contact in microtubules. This is an attractive target for drugs designed to perturb microtubule dynamics by interfacial interference, for which tubulin seems ideally suited because of its propensity to self-assoc.
-
44Iwasaki, K.; Wan, K. K.; Oppedisano, A.; Crossley, S. W. M.; Shenvi, R. A. Simple, chemoselective hydrogenation with thermodynamic stereocontrol J. Am. Chem. Soc. 2014, 136, 1300– 130344https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXotVeksA%253D%253D&md5=cad8e944cc88b12006aeddac5323b186Simple, Chemoselective Hydrogenation with Thermodynamic StereocontrolIwasaki, Kotaro; Wan, Kanny K.; Oppedisano, Alberto; Crossley, Steven W. M.; Shenvi, Ryan A.Journal of the American Chemical Society (2014), 136 (4), 1300-1303CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)Few methods permit the hydrogenation of alkenes to a thermodynamically favored configuration when steric effects dictate the alternative trajectory of hydrogen delivery. Dissolving metal redn. achieves this control, but with extremely low functional group tolerance. Here we demonstrate a catalytic hydrogenation of alkenes that affords the thermodn. alkane products with remarkably broad functional group compatibility and rapid reaction rates at std. temp. and pressure.
Also see:
44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2cXotVGjtg%253D%253D&md5=90592331a16f989ea72607e5172c09b8A Practical and Catalytic Reductive Olefin CouplingLo, Julian C.; Yabe, Yuki; Baran, Phil S.Journal of the American Chemical Society (2014), 136 (4), 1304-1307CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)In the presence of Fe(acac)3 and phenylsilane, dienes with one electron-deficient alkene moiety such as methylpentenylcyclohexenone I underwent chemoselective (and in some cases stereoselective) reductive cyclization/coupling reactions in ethanol or ethanol/ethylene glycol mixts. to give cyclization products such as cis-decalone II regioselectively in 60-97% yields. Under similar conditions, alkenes such as 1-methyl-1-cyclohexene underwent regioselective reductive coupling with electron-deficient alkenes to give products such as III (R = MeCO, MeO2C, Me2NCO, NC, PhSO2; R1 = H, MeO2C) in 34-81% yields. Unactivated olefins were joined directly to electron-deficient olefins in both intra- and intermol. settings to generate hindered bicyclic systems, vicinal quaternary centers, and cyclopropanes which would be difficult or perhaps impossible to access using other methods; the reductive coupling reactions were insensitive to oxygen and moisture. -
45Barker, T. J.; Boger, D. L. Fe(III)/NaBH4-mediated free radical hydrofluorination of unactivated alkenes J. Am. Chem. Soc. 2012, 134, 13588– 1359145https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38XhtFClurnP&md5=9e25b202126788582c1d2f174f43e0ebFe(III)/NaBH4-mediated free radical hydrofluorination of unactivated alkenesBarker, Timothy J.; Boger, Dale L.Journal of the American Chemical Society (2012), 134 (33), 13588-13591CODEN: JACSAT; ISSN:0002-7863. (American Chemical Society)A powerful Fe(III)/NaBH4-mediated free radical hydrofluorination of unactivated alkenes is disclosed using Selectfluor reagent as a source of fluorine and resulting in exclusive Markovnikov addn. In contrast to the traditional and unmanageable free radical hydrofluorination of alkenes, the Fe(III)/NaBH4-mediated reaction is conducted under exceptionally mild reaction conditions (0 °C, 5 min, CH3CN/H2O). The reaction can be conducted open to the air and with water as a cosolvent and demonstrates an outstanding substrate scope and functional group tolerance.
-
46Boger, D. L.; Brotherton, C. E. Total synthesis of azafluoranthene alkaloids: rufescine and imelutine J. Org. Chem. 1984, 49, 4050– 4055There is no corresponding record for this reference.
-
47Duflos, A.; Kruczynski, A.; Baret, J.-M. Novel aspects of natural and modified Vinca alkaloids Curr. Med. Chem., Anti-Cancer Agents 2002, 2, 55– 75There is no corresponding record for this reference.
-
48Campbell, E. L.; Skepper, C. K.; Sankar, K.; Duncan, K. K.; Boger, D. L. Transannular Diels–Alder/1,3-dipolar cycloaddition cascade of 1,3,4-oxadiazoles: total synthesis of a unique set of vinblastine analogues Org. Lett. 2013, 15, 5306– 5309There is no corresponding record for this reference.
-
49Roepke, J.; Salim, V.; Wu, M.; Thamm, A. M. K.; Murata, J.; Ploss, K.; Boland, W.; De Luca, V. Vinca drug components accumulate exclusively in leaf exudates of Madagascar periwinkle Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 15287– 15292There is no corresponding record for this reference.
-
50Once in a while you receive a valued gift if you ask the right question at the right time. Personal communication: Otis, Hutchinson, KS (1971) .There is no corresponding record for this reference.
-