Novel Chiral Auxiliary for Attempted Resolution of Key Roxifiban Intermediate: A Simple Diastereoselective Coupling Approach for the Synthesis of Roxifiban

Abstract

This article describes a simple method for the synthesis of roxifiban, a potent glycoprotein GP IIb‐IIIa receptor antagonist, by a diastereoselective coupling approach to give >99.9% optical purity. We have also described an attempt to resolve the key synthetic intermediate by diastereomeric ester formation. Although we have been able to separate two diastereomeric esters, the removal of the chiral auxiliary led to partial racemization.

Keywords:

• diastereoselective coupling
• 1,9‐dideoxy forskolin
• dynamic kinetic resolution
• glycoprotein IIb‐IIIa receptor
• roxifiban

Acknowledgments

We gratefully acknowledge Swati A. Piramal for her interest and encouragement and Swati Bal‐Tambe and her group for providing analytical data. Finally we acknowledge A. Ranade for providing useful literature input and fruitful discussion.