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

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.

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