An Economical Route to Lamivudine Featuring a Novel Strategy for Stereospecific Assembly
David R. Snead, D. Tyler McQuade, Saeed Ahmad, Rudy Krack, Rodger W. Stringham, Justina M. Burns, Irini Abdiaj, Vijayagopal Gopalsamuthiram, Ryan C. Nelson, B. Frank Gupton
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.