(<i>S</i>)-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 (<i>S</i>)- and (<i>R</i>)-<i>N</i>-(6-hydroxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl) acetamide, two key synthons for the preparation of (<i>S</i>)-pramipexole, an anti-Parkinson drug...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Catalysts |
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| Online Access: | https://www.mdpi.com/2073-4344/10/8/941 |
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| author | Samuele Ciceri Patrizia Ferraboschi Paride Grisenti Shahrzad Reza Elahi Carlo Castellano Matteo Mori Fiorella Meneghetti |
| author_facet | Samuele Ciceri Patrizia Ferraboschi Paride Grisenti Shahrzad Reza Elahi Carlo Castellano Matteo Mori Fiorella Meneghetti |
| author_sort | Samuele Ciceri |
| collection | DOAJ |
| description | A new chemoenzymatic method has been developed for the synthesis of (<i>S</i>)- and (<i>R</i>)-<i>N</i>-(6-hydroxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl) acetamide, two key synthons for the preparation of (<i>S</i>)-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 <i>R</i>-enantiomer, and 31% and >99% ee for the <i>S</i>- one) through a careful optimization of the reaction conditions, starting from the corresponding racemic mixture and using two consecutive irreversible transesterifications, catalyzed by <i>Candida antarctica</i> 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. |
| first_indexed | 2024-03-10T17:21:40Z |
| format | Article |
| id | doaj.art-a6837b72496c4032abefa57910021b8e |
| institution | Directory Open Access Journal |
| issn | 2073-4344 |
| language | English |
| last_indexed | 2024-03-10T17:21:40Z |
| publishDate | 2020-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Catalysts |
| spelling | doaj.art-a6837b72496c4032abefa57910021b8e2023-11-20T10:20:16ZengMDPI AGCatalysts2073-43442020-08-0110894110.3390/catal10080941(<i>S</i>)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric IntermediatesSamuele Ciceri0Patrizia Ferraboschi1Paride Grisenti2Shahrzad Reza Elahi3Carlo Castellano4Matteo Mori5Fiorella Meneghetti6Department of Medical Biotechnology and Translational Medicine, University of Milan, Via C. Saldini 50, 20133 Milano, ItalyDepartment of Medical Biotechnology and Translational Medicine, University of Milan, Via C. Saldini 50, 20133 Milano, ItalyChemical-Pharmaceutical Consulting and IP Management, Viale G. da Cermenate 58, 20141 Milano, ItalyDepartment of Medical Biotechnology and Translational Medicine, University of Milan, Via C. Saldini 50, 20133 Milano, ItalyDepartment of Chemistry, University of Milan, Via C. Golgi 19, 20133 Milano, ItalyDepartment of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, ItalyDepartment of Pharmaceutical Sciences, University of Milan, Via L. Mangiagalli 25, 20133 Milano, ItalyA new chemoenzymatic method has been developed for the synthesis of (<i>S</i>)- and (<i>R</i>)-<i>N</i>-(6-hydroxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl) acetamide, two key synthons for the preparation of (<i>S</i>)-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 <i>R</i>-enantiomer, and 31% and >99% ee for the <i>S</i>- one) through a careful optimization of the reaction conditions, starting from the corresponding racemic mixture and using two consecutive irreversible transesterifications, catalyzed by <i>Candida antarctica</i> 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.https://www.mdpi.com/2073-4344/10/8/941chiral synthonspramipexoledexpramipexoleParkinson’s diseasehypereosinophilic syndromesbiocatalysis |
| spellingShingle | Samuele Ciceri Patrizia Ferraboschi Paride Grisenti Shahrzad Reza Elahi Carlo Castellano Matteo Mori Fiorella Meneghetti (<i>S</i>)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates Catalysts chiral synthons pramipexole dexpramipexole Parkinson’s disease hypereosinophilic syndromes biocatalysis |
| title | (<i>S</i>)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates |
| title_full | (<i>S</i>)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates |
| title_fullStr | (<i>S</i>)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates |
| title_full_unstemmed | (<i>S</i>)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates |
| title_short | (<i>S</i>)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates |
| title_sort | i s i pramipexole and its enantiomer dexpramipexole a new chemoenzymatic synthesis and crystallographic investigation of key enantiomeric intermediates |
| topic | chiral synthons pramipexole dexpramipexole Parkinson’s disease hypereosinophilic syndromes biocatalysis |
| url | https://www.mdpi.com/2073-4344/10/8/941 |
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