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

Catalysts

Paride Grisenti¹  Carlo Castellano²  Patrizia Ferraboschi³  ShahrzadReza Elahi³  Samuele Ciceri³  Fiorella Meneghetti⁴  Matteo Mori⁴ 

[1] Chemical-Pharmaceutical Consulting and IP Management, Viale G. da Cermenate 58, 20141 Milano, Italy;Department of Chemistry, University of Milan, Via C. Golgi 19, 20133 Milano, Italy;Department of Medical Biotechnology and Translational Medicine, University of Milan, Via C. Saldini 50, 20133 Milano, Italy;Department of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, Italy;

关键词: chiral synthons;    pramipexole;    dexpramipexole;    Parkinson’s disease;    hypereosinophilic syndromes;    biocatalysis;   

DOI  :  10.3390/catal10080941

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown