A Unified Total Synthesis of the Immunomodulators (-)-Rapamycin and (-)-27-Demethoxyrapamycin: Assembly of the Common C(1-20) Perimeter and Final Elaboration

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• 作者：Amos B. Smith ; III ; Stephen M. Condon ; John A. McCauley ; Johnnie L. Leazer ; Jr. ; James W. Leahy ; and Robert E. Maleczka ; Jr.
• 刊名：Journal of the American Chemical Society
• 出版年：1997
• 出版时间：February 5, 1997
• 年：1997
• 卷：119
• 期：5
• 页码：962 - 973
• 全文大小：783K
• 年卷期：v.119,no.5(February 5, 1997)
• ISSN：1520-5126

文摘

The potent, naturally occurring immunomodulators(-)-rapamycin (1) and(-)-27-demethoxyrapamycin(2) have been synthesized via a unified and highlyconvergent strategy. In the preceding paper we discussedtheconstruction of common building blocks A-C and their linkage toprovide the C(21-42) segments of 1 and2.Herein we describe model studies of triene generation and hydroxyldeprotection, the preparation and coupling ofbuilding blocks D and E, a two-step protocol for macrocycle formationvia union of the ABC and DE subtargets,and completion of the total syntheses. The synthesis of27-demethoxyrapamycin (2) confirmed the assignedstructure.