Applications of Vinylogous Mannich Reactions. Total Syntheses of the Ergot Alkaloids Rugulovasines A and B and Setoclavine

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• 作者：Spiros Liras ; Christopher L. Lynch ; Andrew M. Fryer ; Binh T. Vu ; and Stephen F. Martin
• 刊名：Journal of the American Chemical Society
• 出版年：2001
• 出版时间：June 27, 2001
• 年：2001
• 卷：123
• 期：25
• 页码：5918 - 5924
• 全文大小：101K
• 年卷期：v.123,no.25(June 27, 2001)
• ISSN：1520-5126

文摘

Concise syntheses of the Ergot alkaloids rugulovasine A (3a), rugulovasine B (3b), and setoclavine(2) have been completed by strategies that feature inter- and intramolecular vinylogous Mannich reactions asthe key steps. Thus, the first synthesis of 3a,b commenced with the conversion of the known indole 17 into24 via the addition of the furan 22 to the iminium ion 21, which was generated in situ from the aldehyde 19.Cyclization of 24 by a novel S_RN1 reaction followed by removal of the N-benzyl group furnished a mixture(1:2) of 3a and 3b. In an alternative approach to these alkaloids, the biaryl 35 was reduced with DIBAL-H togive an intermediate imine that underwent spontaneous cyclization via an intramolecular vinylogous Mannichaddition to provide 36a,b. N-Methylation of the derived benzyl carbamates 37a,b followed by global deprotectiongave a mixture (2:1) of rugulovasines A and B (3a,b). Setoclavine (2) was then prepared from the biaryl 41using a closely related intramolecular vinylogous Mannich reaction to furnish the spirocyclic lactones 42a,b.These lactones were subsequently transformed by hydride reduction and reductive methylation into the ergolinederivatives 43a,b, which were in turn converted into 2 by deprotection and solvolytic 1,3-rearrangement ofthe allylic hydroxyl group.