An Alternative Enzymatic Route to the Ergogenic Ketone Body Ester (R)-3-Hydroxybutyl (R)-3-Hydroxybutyrate

• Published in: Catalysts
• Main Authors: Ferdinando Zaccone, Valentina Venturi, Pier Paolo Giovannini, Claudio Trapella, Marco Narducci, Hugues Fournier, Anna Fantinati
• Format: Text
• Language: English
• Published: Multidisciplinary Digital Publishing Institute 2021
• Subjects: ketone body ester; lipase; kinetic resolution; asymmetric synthesis; configuration inversion; Antarc*; Antarctica
• Online Access: https://doi.org/10.3390/catal11010140

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.