Synthesis of the methylene bis-tetrahydropyran motif of (-)-exiguolide

A chiral-pool approach for the construction of methylene bis-tetrahydropyran subunit, C-1-C-16 fragment, of (-)-exiguolide is described. The synthesis was efficiently accomplished starting from L-glutamic acid and L-aspartic acid involving oxa-Michael reaction and an aldol-driven-reductive etherification as key steps for the formation of tetrahydropyran ring. (C) 2010 Elsevier Ltd. All rights reserved.