All eight stereoisomeric D-glyconic-delta-lactams: Synthesis, conformational analysis, and evaluation as glycosidase inhibitors

An efficient and general synthetic route to all eight stereoisomeric D-glyc ono-delta-lactams has been developed. The strategy involves, as a key step, a stereodivergent delta-lactam formation with configurational retention or inversion at C-4 of a starting gamma-lactone to lead to two epimers of del ta-lactam from one parent gamma-lactone. Conformations of eight glycono-del ta-lactams were examined by X-ray crystallographic analysis and molecular m odeling. Analyses of conformation and glycosidase-inhibition provide useful information for the design of new glycosidase inhibitors.