Chem. Pharm. Bull., 59(4),525-527, April 2011

Communication to the Editor

Synthetic Studies of the Lichen Macrolide Lepranthin. Stereoselective Synthesis of the Diolide Framework Based on Regioselective Epoxide-Opening Reactions

Hisashi TAKADA,^a Shinji NAGUMO,^*,a Eiko YASUI,^a Megumi MIZUKAMI,^b and Masaaki MIYASHITA^*,a

^a Department of Applied Chemistry, Kogakuin University; 2665-1 Nakano, Hachioji, Tokyo 192-0015, Japan: and ^b Hokkaido Pharmaceutical University, School of Pharmacy; 7-1 Katsuraoka, Otaru 047-0264, Japan. * To whom correspondence should be addressed. e-mail: bt13071@ns.kogakuin.ac.jp

Stereoselective synthesis of the 16-membered diolide 27, a fully functionalized congener of lepranthin (1), is described. The requisite five asymmetric carbon centers in monomer 23 were constructed in a highly stereoselective manner by using different epoxide-opening reactions of α,β-unsaturated γ,δ-epoxy esters and epoxy alcohol derivatives as the key steps. The monomer 23 was successfully transformed into the MOM protected diolide 27 by Yamaguchi macrolactonization.

Key words lepranthin; regioselective epoxide-opening reaction; Yamaguchi macrolactonization; dimeric macrolide