Synthesis of alkylated deoxyno irimycin and 1,5-dideoxy-1,5-iminoxylitol analogues: Polar side-chain modification, sulfonium and selenonium heteroatom variants, conformational analysis, and evaluation as glycosidase inhibitors

M.G. Szczepina, B.D Johnston, Y. Yuan, Birte Svensson, B.M. Pinto

    Research output: Contribution to journalJournal articleResearchpeer-review

    Abstract

    The syntheses of N-alkylated deoxynojirimycin and 1,5-dideoxy-1,5-iminoxylitol derivatives having either a D- or an L-erythritol-3-sulfate functionalized N-substituent are reported. The alkylating agent used was a cyclic sulfate derivative, whereby selective attack of the nitrogen atom at the least hindered primary center afforded the desired ammonium salt. In aqueous solution, these salts were configurationally labile at the ammonium center. Sulfonium and/or selenonium analogues of the ammonium salts were prepared by analogous reactions. The chalcogen salts were obtained as mixtures of diastereomers, separable in some cases, differing only in the stereochemistry at the configurationally stable sulfur or selenium atoms. Proof of configuration and conformation of each compound was obtained by detailed NMR experiments. The compounds are six-membered ring analogues of salacinol, a known sulfonium-salt glucosidase inhibitor. Evaluation of the target compounds for enzyme inhibition of the glucosidase enzyme glucoamylase G2 indicated that these compounds were either inactive or, at best, only weak inhibitors of maltose hydrolysis.
    Original languageEnglish
    JournalJournal of the American Chemical Society
    Volume126
    Pages (from-to)12458-12469
    ISSN0002-7863
    Publication statusPublished - 2004

    Fingerprint Dive into the research topics of 'Synthesis of alkylated deoxyno irimycin and 1,5-dideoxy-1,5-iminoxylitol analogues: Polar side-chain modification, sulfonium and selenonium heteroatom variants, conformational analysis, and evaluation as glycosidase inhibitors'. Together they form a unique fingerprint.

    Cite this