Total Synthesis of Piericidin A1 and B1 and Key Analogues

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• 作者：Martin J. Schnermann ; F. Anthony Romero ; Inkyu Hwang ; Eiko Nakamaru-Ogiso ; Takao Yagi ; Dale L. Boger
• 刊名：Journal of the American Chemical Society
• 出版年：2006
• 出版时间：September 13, 2006
• 年：2006
• 卷：128
• 期：36
• 页码：11799 - 11807
• 全文大小：234K
• 年卷期：v.128,no.36(September 13, 2006)
• ISSN：1520-5126

文摘

Full details of the total synthesis of piericidin A1 and B1 and its extension to the preparation ofa series of key analogues are described including ent-piericidin A1 (ent-1), 4'-deshydroxypiericidin A1 (58),5'-desmethylpiericidin A1 (73), 4'-deshydroxy-5'-desmethylpiericidin A1 (75), and the correspondinganalogues 51, 59, 76, and 77 bearing a simplified farnesyl side chain. The evaluation of these key analogues,along with those derived from their further functionalizations, permitted a scan of the key structural featuresproviding new insights into the role of the substituents found in both the pyridyl core as well as the sidechain. A strategic late stage heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fullyelaborated side chain permitted ready access to the analogues in which each half of the molecule couldbe systematically and divergently modified. The pyridyl cores were assembled enlisting inverse electrondemand Diels-Alder reactions of N-sulfonyl-1-azabutadienes, while key elements of side chain synthesesinclude an anti selective asymmetric aldol to install the C9 and C10 relative and absolute stereochemistry(for natural and ent-1) and a modified Julia olefination for formation of the C5-C6 trans double bond withconvergent assemblage of the side chains.