Portal de Periódicos da CAPES

Total Synthesis of Epothilone A through Stereospecific Epoxidation of the p-Methoxybenzyl Ether of Epothilone C

2002; Wiley; Volume: 8; Issue: 16 Linguagem: Inglês

10.1002/1521-3765(20020816)8

1521-3765

Zhi‐Yu Liu, Ze-Cheng Chen, Chengzhi Yu, Ruifang Wang, Ruzhou Zhang, Chusheng Huang, Zheng Yan, Derong Cao, Jianbo Sun, Gang Li,

Chemical synthesis and alkaloids

Chemistry – A European JournalVolume 8, Issue 16 p. 3747-3756 Full Paper Total Synthesis of Epothilone A through Stereospecific Epoxidation of the p-Methoxybenzyl Ether of Epothilone C Zhi-Yu Liu Prof., Zhi-Yu Liu Prof. [email protected] Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorZe-Cheng Chen Dr., Ze-Cheng Chen Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorCheng-Zhi Yu Dr., Cheng-Zhi Yu Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorRui-Fang Wang Dr., Rui-Fang Wang Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorRu-Zhou Zhang Dr., Ru-Zhou Zhang Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorChu-Sheng Huang, Chu-Sheng Huang Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorZheng Yan Dr, Zheng Yan Dr Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorDe-Rong Cao Dr., De-Rong Cao Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorJian-Bo Sun, Jian-Bo Sun Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorGang Li, Gang Li Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this author Zhi-Yu Liu Prof., Zhi-Yu Liu Prof. [email protected] Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorZe-Cheng Chen Dr., Ze-Cheng Chen Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorCheng-Zhi Yu Dr., Cheng-Zhi Yu Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorRui-Fang Wang Dr., Rui-Fang Wang Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorRu-Zhou Zhang Dr., Ru-Zhou Zhang Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorChu-Sheng Huang, Chu-Sheng Huang Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorZheng Yan Dr, Zheng Yan Dr Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorDe-Rong Cao Dr., De-Rong Cao Dr. Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorJian-Bo Sun, Jian-Bo Sun Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this authorGang Li, Gang Li Shanghai Institute of Organic Chemistry Chinese Academy of Sciences 354 Fenglin Lu, Shanghai, 200032 (China) Fax: (+86) 21-641 66 128Search for more papers by this author First published: 09 August 2002 https://doi.org/10.1002/1521-3765(20020816)8:16 3.0.CO;2-ACitations: 28Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat Graphical Abstract Directed α-epoxidation and easy deprotection of 3-O-PMB epothilone C produce epothilone A in high yields (see scheme). Other key steps include epoxide opening with acetylide, modified Wittig reaction of 2 with a ketone bearing a long chain and Jacobsen's KHR for the preparation of the C1–C6 segment. The methodologies used are useful for the synthesis of epothilones and their analogues. Abstract The total synthesis of epothilone A is described by the coupling four segments 4–7 a. Three of the segments, 4, 5 and 7 a, have only one chiral center; all other chiral centers were introduced by simple asymmetric catalytic reactions. The key steps are the ring opening of epoxide 5 with acetylide 8 for the construction of the C12–C13 cis double bond and a practical hydrolytic kinetic resolution (HKR) developed by Jacobsen group for the introduction the chiral center at C3. Especially, the stereospecific epoxidation of 3-O-PMB epothilone C 3 b through long-range effect of 3-O-PMB protecting group gave high yields of the C12–C13 α-epoxide for the synthesis of target molecule. Supporting Information Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2111/2002/f4026_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. References 1 1a G. Höfle, N. Bedorf, K. Gerth, H. Reichenbach, DE 4 138 042, 1993 [ Chem. Abstr. 1993, 120, 52 841]; 1b G. Höfle, N. Bedorf, H. Steinmetz, D. Schomburg, G. Gerth, H. Reichenbach, Angew. Chem. 1996, 108, 1671–1673; Angew. Chem. Int. Ed. 1996, 35, 1567–1569; 1c I. H. Hardt, H. Steinmetz, K. Gerth, F. Sasse, H. Reichenbach, G. Höfle, J. Nat. Prod. 2001, 64, 847–856. 2 Reviews: 2a K. C. Nicolaou, F. Roschangar, D. Vourloumis, Angew. Chem. 1998, 110, 2120–2153; Angew. Chem. Int. Ed. 1998, 37, 2014–2045; 2b J. Mulzer, Monatsh. Chem. 2000, 131, 205–238. 3 3a D. Meng, P. Bertinato, A. Balog, D.-S. Su, T. Kamenecka, E. Sorensen, S. J. Danishefsky, J. Am. Chem. Soc. 1997, 119, 10 073–10 092; 3b K. C. Nicolaou, Y. He, D. Vourloumis, H. Vallberg, F. Roschangar, F. Sarabia, S. Ninkovic, Z. Yang, J. I. Trujillo, J. Am. Chem. Soc. 1997, 119, 7960–7973; 3c K. C. Nicolaou, S. Ninkovic, F. Sarabia, D. Vourloumis, Y. He, H. Vallberg, M. R. V. Finlay, Z. Yang, J. Am. Chem. Soc. 1997, 119, 7974–7991; 3d D. Schinzer, A. Bauer, O. M. Bohm, A. Limberg, M. Cordes, Chem. Eur. J. 1999, 5, 2483–2491; 3e S. C. Sinha, C. F. Barbas III, R. A. Lerner, Proc. Natl. Acad. Sci. USA 1998, 95, 14 603–14 608; 3f S. C. Sinha, J. Sun, G. P. Miller, M. Wartmann, R. A. Lerner, Chem. Eur. J. 2001, 7, 1691–1702; 3g B. Zhu, J. S. Panek, Org. Lett. 2000, 2, 2575–2578; 3h D. Sawada, M. Shibasaki, Angew. Chem. 2000, 112, 215–219; Angew. Chem. Int. Ed. 2000, 39, 209–213; 3i D. Sawada, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2000, 122, 10 521–10 532. 4 J. W. Bode, E. M. Carreira, J. Am. Chem. Soc. 2001, 123, 3611–3612. 5 The Shibasaki group reported the synthesis of epothilone A (1) using multifunctional catalytic asymmetric reactions starting from 2,2-dimethyl-propane-1,3-diol and thiomethacrylic acid (S)-ethyl ester over 23 steps in 0.17 % overall yield and 25 steps in 0.6 % overall yield, see ref. [3h, i], respectively. 6 R. E. Taylor, J. Zajicek, J. Org. Chem. 1999, 64, 7224–7228. 7 7a Z.-Y. Liu, C.-Z. Yu, J. Yang, Synlett 1997, 1383–1384; 7b Z.-Y. Liu, C.-Z. Yu, R.-F. Wang, G. Li, Tetrahedron Lett. 1998, 39, 5261–5264. 8 D. F. Taber, J. B. Houze, J. Org. Chem. 1994, 59, 4004–4006. 9 Y. Gao, R. M. Hanson, J. M. Klunder, S. Y. Ko, H. Masamune, K. B. Sharpless, J. Am. Chem. Soc. 1987, 109, 5765–5780. 10 A. Brandes, U. Eggert, H. M. R. Hoffmann, Synlett 1994, 745–747. 11 F. E. Hooper, T. B. Johnson, J. Am. Chem. Soc. 1934, 56, 470–471. 12 D. Schinzer, A. Limberg, O. M. Boehm, Chem. Eur. J. 1996, 2, 1477–1482. 13 T. Gabriel, L. Wessjohann, Tetrahedron Lett. 1997, 38, 1363–1366. 14 J. De Brabander, S. Rosset, G. Bernardinelli, Synlett 1997, 824–826. 15 B. Panicker, J. M. Karle, M. A. Avery, Tetrahedron 2000, 56, 7859–7868. 16 J. Mulzer, A. Mantoulidis, E. Oehler, J. Org. Chem. 2000, 65, 7456–7467. 17 N. Yoshikawa, Y. M. A. Yamada, J. Das, H. Sasai, M Shibasaki, J. Am. Chem. Soc. 1999, 121, 4168–4178. 18 E. Claus, A. Pahl, P. G. Jones, H. M. Meyer, M. Kalesse, Tetrahedron Lett. 1997, 38, 1359–1362. 19 M. Kalesse, M. Quitschalle, E. Claus, K. Gerlach, A. Pahl, H. H. Meyer, Eur. J. Org. Chem. 1999, 2817–2823. 20 R. E. Taylor, G. M. Galvin, K. A. Hilfiker, Y Chen, J. Org. Chem. 1998, 63, 9580–9583. 21 M. Tokunaga, J. F. Larrow, F. Kakiuchi, E. N. Jacobsen, Science 1997, 277, 936–938. 22 K. Hinterding, E. N. Jacobsen, J. Org. Chem. 1999, 64, 2164–2165. 23 I. Mori, K. Ishihara, C. H. Heathcock, J. Org. Chem. 1990, 55, 1114–1117. 24 Compound 7 b: [α]=−17.7 (c=0.8, CHCl3); lit.:[3c] [α]=+16.1 (c=1.0, CHCl3). Professor Nicolaou indicated in a correspondence that there was a typographical error in ref. [3c] for the optical rotation of 7 b which should indeed be of negative value. 25 Independently, the Avery group used the same acetylide opening epoxide strategy for the synthesis of epothilone A C7–C15 segment: P. Bijoy, M. A. Avery, Tetrahedron Lett. 1998, 39, 209–212. 26 Z. Zhao, G. S. Scarlato, R. W. Armstrong, Tetrahedron 1991, 32, 1609–1612. 27 The salt 6 had independently been used by the Mulzer group to react with a shorter chain ketone to give the E configured double bond compound with some Z isomer in the synthesis of epothilone B, see refs. [16, 26]. 28 K. C. Nicolaou, D. Hepworth, M. R. V. Finlay, N. P. King, B. Werschkun, A. Bigot, Chem. Commun. 1999, 519–520. 29 We thank Professor G. Höfle for kindly providing us with natural samples of epothilone A and C. 30 The Snyder group proposed the epoxide ring at C12–C13 forms an intramolecular cross-ring hydrogen bond with the hydrogen of the 3β-hydroxy group. In that case, the 3β-hydroxy group should direct the α-epoxidation of epothilone C to give epothilone A, although this was not observed in our experiments: M. Wang, X. Xia, Y. Kim, D. Hwang, J. M. Jansen, M. Botta, D. C. Liotta, J. P. Snyder, Org. Lett. 1999, 1, 43–46. 31 During the revision of this manuscript, Fürstner and Avery published their synthesis of epothilone A: A. Fürstner, C. Mathes, Chem. Commun. 2001, 1057–1059; R. M. Hindupur, B. Panicker, M. Valluri, M. A. Avery, Tetrahedron Lett. 2001, 42, 7341–7344. Citing Literature Volume8, Issue16August 16, 2002Pages 3747-3756 ReferencesRelatedInformation