Application of acyl cyanophosphorane methodology to the synthesis of protease inhibitors: poststatin, eurystatin, phebestin, probestin and bestatin

Full details are given for the syntheses of the protease inhibitors, poststatin and eurystatin by the acyl cyanophosphorane coupling procedure used for the formation of alpha-keto amides. We have also extended this methodology to the syntheses of the related alpha-hydroxy amide natural products. phebestin, probestin and bestatin. The key step in the latter synthetic sequences involved diastereomeric selectivity in the reduction of the alpha-keto precursor to the corresponding a-hydroxy amide by the use of zinc borohydride. (C) 2003 Elsevier Ltd. All rights reserved.