Enzymatic Desymmetrisation of Prochiral meso -1,2-Disubstituted-1,2-Diaminoethane for the Synthesis of Key Enantioenriched (−)-Nutlin-3 Precursor

Herein we present the biocatalysed preparation of a mono- N -carbamate-protected precursor of antitumoral Nutlin-3a through enantioselective alkoxycarbonylation of meso -1,2-disubstituted-1,2-diaminoethane using enzyme lipases and dialkyl carbonates as acylating agents. A series of supported or free...

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Bibliographic Details
Published in:Molecules
Main Authors: Virginia Cristofori, Davide Illuminati, Chiara Bisquoli, Martina Catani, Greta Compagnin, Giulia Turrin, Claudio Trapella, Anna Fantinati
Format: Article in Journal/Newspaper
Language:English
Published: MDPI AG 2024
Subjects:
biocatalysis
Nutlin-3a
desymmetrisation
vicinal meso -diamines
Organic chemistry
QD241-441
Antarc*
Antarctica
Online Access:https://doi.org/10.3390/molecules29143267
https://doaj.org/article/59b0a2d3578d4571872fd539124d04e7
Description
Summary:Herein we present the biocatalysed preparation of a mono- N -carbamate-protected precursor of antitumoral Nutlin-3a through enantioselective alkoxycarbonylation of meso -1,2-disubstituted-1,2-diaminoethane using enzyme lipases and dialkyl carbonates as acylating agents. A series of supported or free lipase enzymes were screened in combination with commercially available diallyl, diethyl and dimethyl carbonates. The reactions were conducted at different temperatures, for different reaction times and with variable co-solvent systems to evaluate the effects on the enzyme catalytic activity. The best results in terms of conversion, enantiomeric excess and yield were obtained when lipase from Candida antarctica B (CAL-B) was used with diallyl carbonate (DAC) when conducting the reaction solventless at 75 °C.

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