Development of Novel Chiral Building Blocks and Their Utilization in the Synthesis of Physiologically Active Compounds

本研究的目的是开发高度官能化的手性结构单元及其在合成生理活性物质中的利用，其中我们决定利用单萜香芹酮作为起始原料，因为单萜长期以来被认为是合成结构完全不同的天然产物的有用手性前体。因此，（+）-香芹酮和（-）-香芹酮通过涉及Favorskii型重排的三步反应分别以良好的产率转化为相应的环戊酮衍生物。这种手性环戊酮具有三种不同的官能团，因此可以很容易地实现环戊酮上所有碳原子的化学修饰，基于上述概念，建立了以手性环戊酮为起始原料合成碳青霉烯类抗生素硫霉素的方法。该合成策略也被应用于其1 β-甲基衍生物和其他碳青霉烯类抗生素的合成。此外，还合成了（+）-eldanestine，（-）-cis- whisky lactone，（-）-neonepetalactone和oudemansin A等化合物，其中环戊酮的区域选择性键断裂反应起了重要作用，这些结果表明，环戊酮是一种很容易从单萜香芹酮得到的化合物，是合成各种生理活性化合物的有用的手性合成子。

The object of this study was to develop highly functionalized chiral building blocks and their utilization in the synthesis of physiologically active substances, where we have decided to exploit a monoterpene, carvone, as a starting material, since monoterpenes have long being recognized as useful chiral precursors in the synthesis of quite different structural classes of natural products. Thus (+)-and(-)- carvone were converted into the corresponding cyclopentanone derivatives by three-steps involving the Favorskii type rearrangement, in good yields, respectively. This chiral cyclopentanone has different three types of functional groups, hence the chemical modification of all the carbon atoms on the cyclopentanone could easily beachieved.Based on the above concept, the synthesis of thienamycin, a carbapenem antibiotic, was established starting from the chiral cyclopentanone. The synthetic strategy developed here was also applied to the synthesis of its 1beta-methyl derivative and other carbapenem antibiotics. Furthermore, thy syntheses of (+)-eldanolide, (-)-cis- whisky lactone, (-)-neonepetalactone, and oudemansin A were also achieved, in which a regioselective bond cleavage reaction, newly developed by us, of the cyclopentanone played an important role.These results clearly indicated that the cyclopentanone, readily accessible from a monoterpene, carvone, is a useful chiral synthon in the synthesis of various types of physiologically active compounds.