Synthesis of new six- and seven-membered 1-N-iminosugar as promising glycosidase inhibitors

Abstract

New six- and seven-membered 1-N-iminosugars were prepared from D-glucose by the stereoselective Michael addition of nitromethane to D-glucose derived α,β-unsaturated ester A followed by one pot reduction of nitro/ester functionality and subsequent amine protection to get N-Cbz protected aminol 6. Hydrolysis of 1,2-acetonide and reductive aminocyclization gave seven membered 1-N-iminosugar 5b. While, hydrolysis of 1,2-acetonide followed by NaIO₄ oxidative cleavage and hydrogenation using 10% Pd(OH)₂/C, H₂ gave six membered 1-N-iminosugar 4a; the hydrogenation using 10% Pd/C-H₂ however, gave N-methyl substituted 1-N-iminosugar 4b. The hydrochloride salts of 4a/4b and 5b were found to be specific α-galactosidase and moderate α-glucosidae inhibitors, respectively, in micro molar range.