Norstatines from aldehydes by sequential organocatalytic α-amination and Passerini reaction

The combination of the enantioselective, organocatalytic alpha-animation 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 P-secretase (BACE) 92-102, ((c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006).