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

• Published in: European Journal of Organic Chemistry 2009-02, Vol.2009 (5), p.673-686
• Main Authors: Tarrade‐Matha, Aurélie, Valle, Marcelo Siqueira, Tercinier, Pierre, Dauban, Philippe, Dodd, Robert H.
• Format: Article
• Language: English
• Subjects: Amino ­acids; Aziridines; Chemical reactivity; Chemical Sciences; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Microsclerodermins; Nucleophilic ring‐opening; Organic chemistry; Peptides; Preparations and properties; Reactivity and mechanisms; Synthesis design
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200801000

The efficient synthesis of a protected form of (2S,3R,4S,5S,7E)‐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) The efficient synthesis of a protected form of APTO, the α‐hydroxy β‐amino acid component of microsclerodermins C and D, starting from L‐gulose is reported. Thestrategy is based on treatment of aziridino‐γ‐lactones with soft nucleophiles, which regioselectively affords α‐substituted β‐amino acids.