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.
(S)-Pramipexole and Its Enantiomer, Dexpramipexole : a New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates / S. Ciceri, P. Ferraboschi, P. Grisenti, S. Reza Elahi, C. Castellano, M. Mori, F. Meneghetti. - In: CATALYSTS. - ISSN 2073-4344. - 10:8(2020 Aug 16), pp. 941.1-941.16.
|Titolo:||(S)-Pramipexole and Its Enantiomer, Dexpramipexole : a New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates|
CICERI, SAMUELE (Primo) (Corresponding)
MENEGHETTI, FIORELLA (Corresponding)
|Parole Chiave:||chiral synthons; pramipexole; dexpramipexole; Parkinson’s disease; hypereosinophilic syndromes; biocatalysis; asymmetric synthesis; Candida antarctica Lipase A; irreversible transesterification; crystal structures|
|Settore Scientifico Disciplinare:||Settore BIO/10 - Biochimica|
|Data di pubblicazione:||16-ago-2020|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/catal10080941|
|Appare nelle tipologie:||01 - Articolo su periodico|