( S )-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates

• Published in: Catalysts
• Main Authors: Samuele Ciceri, Patrizia Ferraboschi, Paride Grisenti, Shahrzad Reza Elahi, Carlo Castellano, Matteo Mori, Fiorella Meneghetti
• Format: Article in Journal/Newspaper
• Language: English
• Published: MDPI AG 2020
• Subjects: chiral synthons; pramipexole; dexpramipexole; Parkinson’s disease; hypereosinophilic syndromes; biocatalysis; Chemical technology; TP1-1185; Chemistry; QD1-999; Antarc*; Antarctica
• Online Access: https://doi.org/10.3390/catal10080941; https://doaj.org/article/a6837b72496c4032abefa57910021b8e

A new chemoenzymatic method has been developed for the synthesis of ( S )- and ( R )- N -(6-hydroxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl) acetamide, two key synthons for the preparation of ( S )-pramipexole, an anti-Parkinson drug, and its enantiomer dexpramipexole, which is currently under investigation for the treatment of eosinophil-associated disorders. These two building blocks have been obtained in good yields and high enantiomeric excess (30% and >98% ee for the R -enantiomer, and 31% and >99% ee for the S - one) through a careful optimization of the reaction conditions, starting from the corresponding racemic mixture and using two consecutive irreversible transesterifications, catalyzed by Candida antarctica lipase type A. Single crystal X-ray analysis has been carried out to unambiguously define the stereochemistry of the two enantiomers, and to explore in depth their three-dimensional features.