Total Synthesis of (+)-Calyculin A and (-)-Calyculin B: Cyanotetraene Construction, Asymmetric Synthesis of the C(26-37) Oxazole, Fragment Assembly, and Final Elaboration

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• 作者：Amos B. Smith ; III ; Gregory K. Friestad ; Joseph Barbosa ; Emmanuel Bertounesque ; James J.-W. Duan ; Kenneth G. Hull ; Makoto Iwashima ; Yuping Qiu ; P. Grant Spoors ; and Brian A. Salvatore
• 刊名：Journal of the American Chemical Society
• 出版年：1999
• 出版时间：November 17, 1999
• 年：1999
• 卷：121
• 期：45
• 页码：10478 - 10486
• 全文大小：720K
• 年卷期：v.121,no.45(November 17, 1999)
• ISSN：1520-5126

文摘

A convergent total synthesis leading to (+)-calyculin A and (-)-calyculin B (1 and 2), antipodes ofthe potent, highly selective and remarkably cell-permeable phosphatase inhibitors calyculins A and B, hasbeen achieved. In the preceding paper we outlined the asymmetric synthesis of the C(9-25) spiroketaldipropionate subunit (+)-BC; herein we describe construction of the C(1-8) cyanotetraene, an asymmetricsynthesis of the C(26-37) oxazole, fragment assembly and final elaboration to (+)-1 and (-)-2. Highlights ofthe synthesis include: application of a one-pot three-component Suzuki reaction for the construction ofphosphonate A, a bifunctional triene precursor of the light sensitive C(1-8) cyanotetraene subunit, an asymmetricsynthesis of the C(26-32) oxazole (-)-D, exploiting the Silks-Odom ⁷⁷Se NMR protocol to assess enantiomericpurity, construction of the C(33-37) subtarget (-)-E in a highly stereocontrolled fashion via an acyliminiumion, and a concise, highly efficient sequence for fragment assembly and elaboration to (+)-calyculin A and(-)-calyculin B. The synthesis of (-)-2 also confirms the structure of calyculin B, previously based only onspectral comparison with calyculin A.