Racemic perhexiline has been used (or is currently undergoing clinical trials) for the treatment of a variety of cardiovascular disorders. Increasing evidence suggests that the (–)-enantiomer should be used, as opposed to the racemic mixture. Here, we report the first asymmetric synthesis of both enantiomers of perhexiline in high enantiomeric excess and the assignment of their (–)-S/(+)-R absolute stereochemistry by X-ray crystallography.
Bibliographical noteWe gratefully thank Signal Pharma for financial support and fellowship (C.C.T), and the EPSRC National Mass Spectrometry Service Centre (Swansea, UK) for performing HRMS analyses. We thank Prof Michael Frenneaux (University of East Anglia, Norwich, UK) for useful and stimulating discussions.
- asymmetric analysis
- medicinal chemistry
- crystal structure