Synthesis of alpha- and beta-glycosyl asparagine ethylene isosteres (C-glycosyl asparagines) via sugar acetylenes and Garner aldehyde coupling.

Abstract

A convergent approach has been developed for the synthesis of C-glycosyl amino acids in which the glycinyl moiety CH(NH2)CO2H is connected to the anomeric center of the sugar residue by a three carbon atom tether. Essentially, these compounds are isosteres of N-glycosyl asparagines in which the amide group has been replaced by an ethylene bridge. Following the coupling of alpha- or beta-D-linked lithium C-glycoside acetylides with N-Boc D-serinal acetonide (Garner aldehyde), the resulting adducts were transformed into the final N-Boc-C-glycosyl-alpha-aminopentanoic acids via reduction of the triple bond, deoxygenation, and oxidative cleavage of the oxazolidine ring. By this protocol, 12 C-glycosyl asparagines, six pairs of alpha- and beta-anomers, have been prepared incorporating the gluco, galacto, manno, and the corresponding 2-acetamido-2-deoxy residues.