Concise asymmetric syntheses of the cylindrospermopsin alkaloids

Abstract

Presented herein is a concise 18 step asymmetric synthesis of the hepatotoxic cyanobacterial alkaloids cylidrospermopsin, 7-epi-cylindrospermopsin, and the purported structure of 7-deoxycylindrospermopsin. Born from a simple amino acid, an intramolecular [1,3]-dipolar cycloaddition of an α-alkoxycarbonyl nitrone and a nitroaldol reaction serve to construct these natural products from a single stereocenter. The brevity of the synthesis, and the incorporation of the uracil moiety in a late-stage approach, proffers the ability to generate synthetic analogues that have been deployed for biomechanistic evaluation.