Enantiospecific Synthesis of a Protected Equivalent of APTO, the β‐Amino Acid Fragment of Microsclerodermins C and D, by Aziridino‐γ‐lactone Methodology

The efficient synthesis of a protected form of (2 S ,3 R ,4 S ,5 S ,7 E )‐3‐amino‐8‐phenyl‐2,4,5‐trihydroxyoct‐7‐enoic acid (APTO), the α‐hydroxy β‐amino acid component of microsclerodermins C and D, 23‐membered cyclic peptides isolated from lithistid sponges, is described. The strategy is based on the preparation of the aziridino‐γ‐lactone 46 from L ‐gulose by a procedure previously developed in our laboratory for simpler substrates. Regioselective opening of the aziridine at C‐2 by acetate anion, an intrinsic reactivity pattern of aziridino‐γ‐lactones, followed by a Heck reaction to install the terminal phenyl group, provides lactone 48 . This, a lactonized form of APTO, can be considered an activated building block for the synthesis of microsclerodermins C and D or their analogues, as demonstrated by its subsequent reaction with a benzylamine to give the carboxamide 51 . This represents the first example of the use of an aziridino‐γ‐lactone for the stereoselective synthesis of an α‐substituted β‐amino acid derivative. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)