An Economical Route to Lamivudine Featuring a Novel Strategy for Stereospecific Assembly

Org Process Res Dev. 2020 Jun 19;24(6):1194-1198. doi: 10.1021/acs.oprd.0c00083. Epub 2020 Apr 7.

Abstract

An economical synthesis of lamivudine was developed by employing a new method to establish the stereochemistry about the heterocyclic oxathiolane ring. Toward this end, an inexpensive and readily accessible lactic acid derivative served the dual purpose of activating the carbohydrate's anomeric center for N-glycosylation and transferring stereochemical information to the substrate simultaneously. Both enantiomers of the lactic acid derivative are available, and either β-enantiomer in this challenging class of 2'-deoxynucleoside active pharmaceutical ingredients can be formed.