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Title
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Strecker-derived methodology for library synthesis of N-acylated alpha-aminonitriles
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Author
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Abstract
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| The Strecker reaction is a three-component condensation of an aldehyde, an amine, and hydrogen cyanide, delivering an a-amino carbonitrile. Despite extensive investigations, the possibility to use amides instead of amines as one of the three condensation partners has been largely neglected. Nonetheless, the N-acylated alpha-aminocarbonitriles that are obtained in this way are of direct interest for drug discovery, because they make up a well-known class of mechanism-based inhibitors of serine- and cysteine-type hydrolases. In response, we have thoroughly explored the corresponding variant of the Strecker reaction, focusing on catalyst use, solvent, reaction time, and cyanide source. Optimized parameters were combined in a sequential one-pot protocol for which the scope was found to be compatible with library synthesis applications. Product yields ranged from 7 to 90%, and conditions were found to be mild and tolerant to a wide range of functional groups, including moieties that are typically present in druglike molecules. |
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Language
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English
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Source (journal)
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ACS Omega
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Publication
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American Chemical Society
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2021
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ISSN
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2470-1343
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DOI
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10.1021/ACSOMEGA.0C04908
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Volume/pages
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6
:2
(2021)
, p. 1328-1338
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ISI
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000612348300032
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Pubmed ID
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33490792
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Full text (Publisher's DOI)
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Full text (open access)
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