The Staudinger/aza-Wittig/Grignard reaction as key step for the concise synthesis of 1-C-Alkyl-iminoalditol glycomimetics

Abstract

The scope of a one-pot tandem approach for the synthesis of C-1 alkyl iminoalditol derivatives with a Staudinger/aza-Wittig/Grignard cascade has been evaluated. The reaction conditions have been optimized for two azidodeoxy aldose substrates and a range of Grignard reagents. The nature of both, substrate as well as nucleophile, was found to control the stereoselectivity of the alkyl addition to the cyclic iminium intermediate at position C-1. This approach enabled the synthesis of a collection of C-alkyl iminoalditols, which were biologically evaluated as inhibitors against a set of standard glycoside hydrolases. All compounds were found to exhibit highly selective inhibition of β-glucosidase activity.

Keywords: C-glycoside iminosugars; Glycomimetics; Staudinger/aza Wittig/Grignard reaction cascade; β-glucosidase inhibitors.