Norstatines from Aldehydes by sequential organocatalytic α-amination and passerini reaction

Abstract

The combination of the enantioselective, organocatalytic α-amination of aldehydes by diazodicarboxylates and the Passerini reaction provides rapid access to norstatine-based peptidomimetics. These intermediates were elaborated further by deprotection and cleavage of the N-N bond to provide useful building blocks for aspartic protease inhibitors. Coupling of the compounds 76-86 with the mono-isophthalamide 91 provided moderate inhibitors of human β-secretase (BACE) 92-102. © Wiley-VCH Verlag GmbH & Co. KGaA, 2006.