Optimizing Arginine for Enantioselectivity in Warfarin Synthesis

Abstract

Warfarin is an anticoagulant medication that is important for the treatment and prevention of blood clots and clotting-related disorders. While it is typically prescribed as a racemic mixture, the R- and S- enantiomers of warfarin have large differences in their anti-coagulant activities. In previous work, it was demonstrated that L-arginine is an effective catalyst in an enantioselective synthesis of Warfarin. The aim of this study is to determine whether various derivatives of L-arginine can promote a more enantioselective synthesis of Warfarin. Using nine L-arginine derivatives, separate warfarin reactions were created and allowed to run for a week. Thin Layer Chromatography (TLC), Flash Chromatography, and High-Performance Liquid Chromatography (HPLC) techniques were applied to determine, isolate, and assess the production of warfarin in each reaction. In cases where low enantioselectivities were observed, an acetic acid-assisted strategy was investigated for its potential to increase enantioselectivities. Data collected from the research suggested no substantial increase in percent yield and no significant assistance to enantioselectivity. Although the research revealed that the L-arginine derivatives investigated in this study did not present any enhancements in selectivity for the R-enantiomer, a comparison of L-arginine and L-citrulline indicated the importance of the guanidinium amine groups in L-arginine for driving its organocatalytic activity.