A simple and efficient method for the stereoselective synthesis of nojirimycin α--glycoside derivatives has been developed using a bicyclic carbamate-type sp-iminosugar, whose preparation on a gram scale has been optimized, as the starting material. sp-iminosugar -glycosides or anomeric esters serve as excellent precursors of acyliminium cations, which can add nucleophiles, including -nucleophiles. The stereochemical outcome of the reaction is governed by stereoelectronic effects, affording the target α-anomer with total stereoselectivity. Thus, the judicious combination of -allylation, carbamate hydrolysis, cross-metathesis, and hydrogenation reactions provides a very convenient entry to iminosugar α--glycosides, which have been transformed into ,-biantennary derivatives by reductive amination or thiourea-forming reactions. The thiourea adducts undergo intramolecular cyclization to bicyclic iminooxazolidine iminosugar α--glycosides upon acid treatment, broadening the opportunities for molecular diversity. A preliminary evaluation against a panel of commercial glycosidases validates the approach for finely tuning the inhibitory profile of glycomimetics.
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| http://dx.doi.org/10.1021/acsomega.2c01469 | DOI Listing |
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