A facile synthesis of 6-deoxydapagliflozin

摘要

A facile synthesis of a potent SGLT2 inhibitor, 6-deoxydapaglifiozin, from methyl 2,3,4-tri-O-benzyl-6-deoxy-6-iodo-α-D-glucopyranoside in six steps with an overall yield of 50 % is described. The key steps were the reductive deiodination of the starting iodide under hydrog-enolytic conditions to build the desired 6-deoxyglucose functionality, the coupling of 2,3,4-tri-O-benzyl-6-deoxy-D-gluconolactone and (5-bromo-2-chlorophenyl)(4-efhoxy-phenyl)methane, followed by BF3·Et2O-mediated reduction with Et3SiH in order to construct the desired anomeric p-configuration. A variety of methods used for the cleavage of benzyl groups in 2,3,4-tri-O-benzyl-1-[4-chloro-3-(4-eth-oxybenzyl)phenyl]-1,6-dideoxy-β-D-glucopyranose were intensively screened, leading to the discovery of AlCl3-mediated cleavage as the optimal method.