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.

这项研究的目的是根据理论计算开发多环天然产物（例如类固醇骨骼）的新合成方法。在本报告的第一部分中，检查了使用无环中间人的串联自由基环化的类固醇BCD环系统的方法。使用串联自由基环化和随后的氰氢烷基化来实现类固醇BCD环系统的有效合成。在第二部分中，研究了使用十元中间体的串联跨跨性自由基环化来实现类固醇BCD环骨骼的方法。通过十元中间体的串联自由基环化，在一锅操作中完成了类固醇BCD环系统的立体选择性合成。在第三部分中，检查了使用自由环化 - 氧捕获反应的维生素D_3的CD环系统方法，并在第四部分中实现了维生素D_3 CD-RING的立体选择性合成，这是一种新的合成方法，用于使用自由基和肛门元素间介质的序列旋转系统进行类固醇CD环的系统。通过同一合成中间体的顺序自由基和阴离子环化来实现两种不同类型的类固醇CD环系统，在最后一部分中，我们将注意力集中在经跨性别的氧化氧化型重排上。类固醇CD环系统的立体选择性合成是使用10元的1,5-二烯系统和随后的Aldol凝结的跨型氧气重排完成的。利用“ MM2过渡状态模型”的构象分析预测了自由基环化和氧气重排的立体选择性。通常，基于MM2过渡状态模型的立体化学控制的考虑可能在关键合成中间体的设计中具有预测价值。