A practical diastereoselective synthesis of ( −)‐bestatin

Diastereoselective addition of nitromethane to Boc‐D‐Phe‐H in the presence of sodium hydride in diethyl ether/hexane containing 15‐crown‐5 and subsequent N,O‐protection with 2,2‐dimethoxypropane gave trans‐oxazolidine in a diastereomeric ratio of >16:1. The oxazolidine was easily separated by column chromatography, which after Nef reaction was coupled to H‐Leu‐OtBu. The 8‐step synthesis afforded (−)‐bestatin in an overall yield of 24.7% after deprotection and ion exchange. An 8‐step diastereoselective synthesis of (−)‐bestatin is developed via nitro‐aldol reaction in a nonpolar solvent followed by cyclization to trans‐oxazolidine in a highly diastereoselective manner (dr >16:1).
Source: Journal of Peptide Science - Category: Biochemistry Authors: Tags: RESEARCH ARTICLE Source Type: research