Diana I. S. P. Resende; Amalia M. Estévez; André M. Alker; Rainer E. Martin; Hans Peter Wessel
Med. J. Chem., 2018, 7(2), 135-144
https://doi.org/10.13171/mjc72/01809051415-wessel

Abstract

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.