1991 Fiscal Year Final Research Report Summary

Synthesis of Cyclopentane-Macrolides Based on Lewis Acid Mediated Cyclization of Chiral Epoxy-Alcohols

Research Project

Project/Area Number	01571137
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Chemical pharmacy
Research Institution	Tohoku University
Principal Investigator	YATAKEYAMA Susumi Tohoku University Pharmaceutical Institute Research ASsociate, 薬学部, 助手 (20143000)
Project Period (FY)	1989 – 1991
Keywords	Sharpless asymmetric epoxidation / Lewis acid mediated cyclization / Substituted cyclopentane / Enantiocontrolled synthesis / Brefeldin A / Brefeldin C / Macrolide antibiotic / Chiral epoxy-alcohol
Research Abstract	In the course of investigation concerning intramolecular Lewis acid mediated nucleophilic opening of epoxy-alcohols, we have developed an enantioselective route to a substituted cyclopentane 2 from an allyl alcohol 1 through four manipulations ; i)Sharpless asymmetric epoxidation, ii)Lewis acid mediated cyclization ; iii)protection as acetonide ; iv)ozonolysis followed by base-catalyzed epimerization. The generality of this method was proved by the fact that regardless of the stereo- and regio-chemistry of pre-exsisting substituents(R^1 and/or R^2)of 1, tri- or four-substituted cyclopentanes 2 with 1, 2-trans configuration were obtained in high enantiomeric excess(>90% ee). The synthetic utility of this method was demonstrated by the achievement of enantiocontrolled syntheses of(+)-brefeldin A(3)and(+)-brefeldin C(4)from 2(R^1=H, R^2=OBn or R^1=R^2=H). brefeldin C(4)from 2(R'=H, R2=OBn or RI=R2=H).

(4 results)