Synthesis of Imino Sugar Scaffolds for the Generation of Glycosidase Inhibitor Libraries

We have synthesized imino sugar scaffolds bearing two points of diversity — the stereocenters located in α positions relative to the nitrogen atom — and three points of orthogonal derivatization — a carboxylic function, the primary hydroxy group, and the ring nitrogen atom. The key steps in the synthetic approach are the chain elongation of aldehyde 5 with the formation of an α,β‐unsaturated ester, the Michael addition of an amine, and the final cyclization. This strategy leads to the preparation of different N ‐substituted imino sugar analogues having both α and β structures and of both D and L stereochemistry. Different derivatives have been prepared from the scaffolds we obtained. The carboxymethyl group was coupled to the amino function of different amino acids to afford compounds 30 − 34 , while the selectively accessible primary hydroxy group has been substituted with an azido group to afford compounds 24 − 26 . (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)