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

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 invest...

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Bibliographic Details
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
Description
Summary: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.

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