Synthesis of the Azetidinyl-Thiazoline Fragment of Vioprolides A and C

Abstract

An efficient synthesis of the azetidinyl-thiazoline fragment of the antifungal and cytotoxic macrolides vioprolides A and C is reported. Key steps of the synthesis include formation of the thiazoline by condensation of N-Alloc- trans (2S,4R)-4-methylazetidine-2-carbonitrile with L-cysteine and formation of the four-membered ring by intramolecular alkylation of a suitably protected N-Alloc derivative prepared from (R)-alaninol. Keywords: Azetidines, natural products, antifungal metabolites