An alternative enzymatic route to the ergogenic ketone body ester (R)-3-hydroxybutyl (r)-3-hydroxybutyrate

• Published in: Catalysts
• Main Authors: Zaccone F., Venturi V., Giovannini P. P., Trapella C., Narducci M., Fournier H., Fantinati A.
• Other Authors: Zaccone, F., Venturi, V., Giovannini, P. P., Trapella, C., Narducci, M., Fournier, H., Fantinati, A.
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2021
• Subjects: Asymmetric synthesi; Configuration inversion; Ketone body ester; Kinetic resolution; Lipase; Antarc*; Antarctica
• Online Access: https://hdl.handle.net/11392/2448437; https://doi.org/10.3390/catal11010140; https://www.mdpi.com/2073-4344/11/1/140

Recent studies have highlighted the therapeutic and ergogenic potential of the ketone body ester, (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate. In the present work, the enzymatic synthesis of this biological active compound is reported. The (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate has been produced through the transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol by exploiting the selectivity of Candida antarctica lipase B (CAL-B). The needed (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate achieved by acetylation with vinyl acetate, also in this case, thanks to the enantioselectivity of the CAL-B used as catalyst. Finally, the stereochemical inversion of the unreacted (S) enantiomers of the ethyl 3-hydroxybutyate and 1,3-butanediol accomplished by known procedure allowed to increase the overall yield of the synthetic pathway by incorporating up to 70% of the starting racemic reagents into the final product.