Nagavaram Narsimha Rao

Synthesis of the macrocyclic core of iriomoteolide 3a.

The asymmetric synthesis of the fully functionalized macrocyclic core of iriomoteolide 3a, a cytotoxic 15-membered macrolide, is disclosed. The key steps involve Sharpless asymmetric dihydroxylation, Sharpless asymmetric epoxidation, olefin cross-metathesis, Yamaguchi esterification, and a ring-closing metathesis reaction for macrocyclization.

Formal total synthesis of (−)-exiguolide

The formal total synthesis of (−)-exiguolide through the chiral-pool approach is described. The key reactions involved for formation of the macrocyclic core from two subunits are Julia–Kocienski olefination and Yamaguchi macrolactonization. The major methylene bis-tetrahydropyran fragment was achieved in a convergent manner from L-glutamic acid and L-aspartic acid involving the oxa-Michael reaction and an aldol-driven reductive etherification as key steps for the formation of a tetrahydropyran ring. The other sulfone subunit was prepared via an Evans aldol reaction.