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

• Published in: Molecules (Basel, Switzerland) Vol. 29; no. 14; p. 3267
• Main Authors: Cristofori, Virginia, Illuminati, Davide, Bisquoli, Chiara, Catani, Martina, Compagnin, Greta, Turrin, Giulia, Trapella, Claudio, Fantinati, Anna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10-07-2024
• Subjects: Biocatalysis; Cancer; Cell cycle; desymmetrisation; Enzymes; Enzymes, Immobilized - chemistry; Fungal Proteins - metabolism; Lipase - chemistry; Lipase - metabolism; Molecular Structure; Nutlin-3a; Piperazines - chemical synthesis; Piperazines - chemistry; Proteins; Solvents - chemistry; Stereoisomerism; vicinal meso-diamines; vicinal meso-diamines; Nutlin-3a; desymmetrisation; biocatalysis
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules29143267

Herein we present the biocatalysed preparation of a mono-
-carbamate-protected precursor of antitumoral Nutlin-3a through enantioselective alkoxycarbonylation of
-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
(CAL-B) was used with diallyl carbonate (DAC) when conducting the reaction solventless at 75 °C.