Total Synthesis of (+)-Fendleridine (Aspidoalbidine) and (+)-1-Acetylaspidoalbidine

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• 作者：Erica L. Campbell ; Andrea M. Zuhl ; Christopher M. Liu ; Dale L. Boger
• 刊名：Journal of the American Chemical Society
• 出版年：2010
• 出版时间：March 10, 2010
• 年：2010
• 卷：132
• 期：9
• 页码：3009-3012
• 全文大小：255K
• 年卷期：v.132,no.9(March 10, 2010)
• ISSN：1520-5126

文摘

A total synthesis of the Aspidosperma alkaloids (+)-fendleridine and (+)-1-acetylaspidoalbidine is detailed, providing access to both enantiomers of the natural products and establishing their absolute configuration. Central to the synthetic approach is a powerful intramolecular [4+2]/[3+2] cycloaddition cascade of a 1,3,4-oxadiazole in which the pentacyclic skeleton and all the stereochemistry of the natural products are assembled in a reaction that forms three rings, four C−C bonds, and five stereogenic centers including three contiguous quaternary centers, and introduces the correct oxidation state at C19 in a single synthetic operation. The final tetrahydrofuran bridge is subsequently installed in one step, enlisting an intramolecular alcohol addition to an iminium ion generated by nitrogen-assisted opening of the cycloadduct oxido bridge, with a modification that permits release of useful functionality (a ketone) at the cleavage termini.