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A carbohydrate-derived trifunctional scaffold for medicinal chemistry library synthesis

Diana I. S. P. Resende, Amalia M. Estévez, Andre M. Alker, Rainer E. Martin, Hans Peter Wessel


For the generation of compound libraries for drug discovery a central scaffold containing three exit vectors with defined chirality was devised starting from commercially available tri-O-acetyl-glucal. Surprisingly, the reaction of a 4-O-mesylate with sodium azide did not lead to the expected 4-azido-4-deoxy derivative but to a 3-azido-3-deoxy regioisomer via intermediate epoxide formation. The absolute stereochemical configuration of the final tetrahydropyran building block was proven by X-ray crystallography. This scaffold endowed with a carboxylic acid, a secondary alcohol, and an azide functionality may be connected to a DNA tag at any of the three distinct exit vectors, thus providing ready access to several different compound libraries. 

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- Crystallographic data for the structure in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication numbers CCDC 1836178. This data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44(0)-1223-336033 or e-mail: deposit@].


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