An improved synthesis of latanoprost involving effective control on 15(S) diastereomer

Abstract

An improved process for the synthesis of latanoprost having excellent optical purity (de 99.9%, [α]_D²⁰ = +35.37° (c = 0.90, acetonitrile)) without use of preparative HPLC is described. This process involves effective purification of hydroxyl intermediate (5A) through solvent crystallization followed by inhibition of inversion of the chiral center at C-15 position. This was possible due to judicious use of diol intermediate (6) for double bond reduction prior to hydroxyl protection.

GRAPHICAL ABSTRACT

KEYWORDS:

• Crystallization
• diol intermediate
• ketone intermediate
• latanoprost
• p-nitrobenzoyl chloride
• preparative HPLC

Acknowledgments

We acknowledge Dr. Arun Natu, Dr. Rajeev Chikate, Dr. Rajesh Vyas and Dr. Himanshu Godbole for their valuable guidance, support and suggestions. The authors are thankful to analytical support team for sample analysis. The authors are also thankful to the M/S Lupin Limited for the research program and Ph.D. registration.