Abstract
6-Hydroxy-8-chlorooctanoate ethyl ester, an intermediate of α-lipoic acid, was synthesized
via a chemoenzymatic method. High-throughput screening revealed that keto reductase
HGD-1 could effectively catalyze the preparation of 6-hydroxy-8-chlorooctanoate ethyl
ester, achieving a substantial conversion rate. The reaction conditions were optimized
subsequently, the parameters for the complexation reaction were established as follows:
a weight of AlCl3 1.8 times that of the substrate; a reaction time of 4 h; a temperature range of 20–25
°C. The parameters for the enzyme-catalyzed reaction were as follows: a temperature
range of 25–30 °C; a reaction time of 4 h; a solution pH of 6.5–7.5; a substrate concentration
of 50 g/L; concentrations of keto reductase HGD-1, coenzyme glucose dehydrogenase,
and nicotinamide adenine dinucleotide phosphate of 3 g/L, 4 g/L, and 0.05 g/L, respectively.
Under these optimal conditions, the substrate conversion rate exceeded 95%, and 92%
yield of 6-hydroxy-8-chlorooctanoate ethyl ester is obtained, suggesting a viable,
eco-friendly method for synthesizing α-lipoic acid, and it provides a green process
route for the industrial production of α-lipoic acid.
Key words
α-lipoic acid - keto reductase - chemoenzymatic method - 6-hydroxy-8-chlorooctanoate
ethyl ester - green technology
