title: Synthesis of new six- and seven-membered 1-N-iminosugars 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 NaIO(4) oxidative cleavage and hydrogenation using 10% Pd(OH)(2)/C, H(2) gave six membered 1-N-iminosugar 4a; the hydrogenation using 10% Pd/C-H(2) 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.
authors: Garware Research Centre, Department of Chemistry, University of Pune, Pune 411 007, India.
authors: Amit M
authors: AM
authors: Jabgunde
authors: Navnath B
authors: NB
authors: Kalamkar
authors: Sanjay T
authors: ST
authors: Chavan
authors: Sushma G
authors: SG
authors: Sabharwal
authors: Dilip D
authors: DD
authors: Dhavale
mesh_terms: D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005947:Glucose / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D050112:Imino Pyranoses / Q000737:chemistry; D050111:Imino Sugars / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: D004791:Enzyme Inhibitors; D050112:Imino Pyranoses; D050111:Imino Sugars; C098432:isofagomine; D006026:Glycoside Hydrolases; D005947:Glucose