Cyclodepsipeptide alveolaride C: total synthesis and structural assignment

Abstract

First stereoselective total synthesis of naturally occurring bioactive cyclodepsipeptide alveolaride C has been achieved using a convergent approach. This synthetic study enabled us to establish unambiguously the stereochemistry of three unassigned chiral centres embedded in the nonpeptidic segment as well as revised the stereochemistry of the proposed β-phenylalanine counterpart of the molecule. The key strategic features of this synthesis include Sharpless asymmetric dihydroxylation for installing the vicinal diol moiety, Julia–Kocienski olefination for constructing the aliphatic side chain, the Shiina protocol for intermolecular esterification, amide coupling and macrolactamization for the ring formation.