Total Synthesis of a Lactam Glycosidase Inhibitor Precursor

Abstract

A total synthesis of an α,β-unsaturated γ-lactam is presented. This heterocycle is a precursor to a glycosidase inhibitor. Glycosidases function in the breakage of complex carbohydrates, yielding smaller sugars for cellular metabolism. Glycosidase inhibitors cripple the enzymatic activity by lodging themselves in the enzyme?s activation site. Heterocycles, due to their sugar-like appearance, form a wide variety of glycosidase inhibitors. The first step of the synthesis is the formation of the ?crotonic? cyanohydrin. Utilizing oxynitrilase, a robust enzyme found in almonds, we are able to induce asymmetry in the α,β-unsaturated aldehyde in exceptional enantiomeric purity. The first generation Grubbs catalyst was utilized to promote the ring closing metathesis. Palladium (0) induced the 1,3 chiral transfer, which, we feel, will allow for the methanol mediated acyl-transfer from the azido lactone to the γ-lactam final product.