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Development of New Synthetic Methods for Steroid Sleketon Based on Theoretical Calculation

基于理论计算的类固醇骨架合成新方法的开发

基本信息

批准号：
08555227
负责人：
TAKAHASHI Takashi
金额：
$ 2.69万
依托单位：
TOKYO INSTITUTE OF TECHNOLOGY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

Objective of this study is to develop new synthetic methodologies for polycyclic natural products such as steroid skeleton based on theoretical calculations. In the first part of this report, the approach to the steroid BCD-ring system using tandem radical cyclization of the acyclic intermediate was examined. An efficient synthesis of steroid BCD-ring system was accomplished using a tandem radical cyclization and subsequent cyanohydrin alkylation. In the second part, another approach to the steroid BCD-ring skeleton using tandem transannular radical cyclization of the ten-membered intermediate was examined. By the tandem radical cyclization of the ten-membered intermediate, stereoselective synthesis of steroid BCD-ring system was accomplished in a one-pot operation. In the third part, the approach to the CD-ring system of vitamin D_3 using radical cyclization-oxygen trapping reaction was examined and stereoselective synthesis of the vitamin D_3 CD-ring was achieved, In the fourth part, a new synthetic method for steroid CD-ring system using sequential cyclization of radical and anionic intermediates was examined. Construction of two different types of steroid CD ring systems was accomplished by the sequential radical and anionic cyclization from same synthetic intermediate, In the last part, we focused our attention on a transannular Oxy-Cope rearrangement. Stereoselective synthesis of steroid CD-ring system was accomplished using transannular Oxy-Cope rearrangement of ten-membered 1,5-diene systems and subsequent aldol condensation. Conformational analysis utilizing the "MM2 transition-state model" predicts the stereoselectivity in the radical cyclization and Oxy-Cope rearrangement. In general, considerations of stereochemical control based on MM2 transition-state model might have predictive value in the design of key synthetic intermediates.

本研究的目的是在理论计算的基础上开发多环天然产物如甾体骨架的新合成方法。在本报告的第一部分中，我们研究了通过串联自由基环化来合成类固醇BCD-环体系的方法。通过串联自由基环化和随后的氰醇烷基化反应，实现了甾体BCD环系的高效合成。在第二部分中，我们研究了另一种合成甾体BCD环骨架的方法，即通过十元中间体的串联跨环自由基环化反应。通过十元中间体的串联自由基环化反应，一锅法完成了甾体BCD环系的立体选择性合成。第三部分探讨了利用自由基环化-氧捕获反应合成维生素D_3CD-环体系的方法，实现了维生素D_3CD-环的立体选择性合成。第四部分研究了自由基环化和阴离子中间体顺序环化合成甾体CD-环体系的新方法。从相同的合成中间体出发，通过连续的自由基和阴离子环化反应，构建了两种不同类型的甾体CD环体系。最后，我们将注意力集中在跨环氧-钴重排反应上。通过十元1，5-二烯体系的跨环氧-钴重排和随后的羟醛缩合反应完成了甾体CD-环体系的立体选择性合成。用“MM2过渡态模型”进行构象分析，预测了自由基环化和氧位重排中的立体选择性。总的来说，基于MM2过渡态模型的立体化学控制的考虑在关键合成中间体的设计中可能具有预测价值。