|Title||The Staudinger/aza-Wittig/Grignard reaction as key step for the concise synthesis of 1-C-Alkyl-iminoalditol glycomimetics|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Zoidl, M, Santana, AGonzalez, Torvisco, A, Tysoe, C, Siriwardena, A, Withers, SG, Wrodnigg, TM|
|Date Published||JUN 24|
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 beta-glucosidase activity. (C) 2016 Elsevier Ltd. All rights reserved.