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功能化的手性构筑块及其在合成生理活性物质中的应用，我们决定以一种单萜类化合物香芹酮为起始原料，因为单萜类化合物长期以来一直被认为是合成不同结构类别的天然产物的有用手性前体。因此，(+)-香芹酮和(-)-香芹酮分别通过涉及Favorskii类型重排的三步反应以较高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，因此可以很容易地对环戊酮上的所有碳原子进行化学修饰。基于上述概念，从手性环戊酮出发，建立了碳青霉烯类抗生素硫那霉素的合成方法。所开发的合成策略也应用于其1-β-甲基衍生物和其他碳青霉烯类抗生素的合成。此外，我们还合成了(+)-榄香内酯、(-)-顺式威士忌内酯、(-)-新内酯和外消旋素A，其中我们新开发的环戊酮的区域选择性断键反应起到了重要的作用。这些结果清楚地表明，环戊酮是一种在合成各种生理活性化合物中很有用的手性合成子。

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.