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Synlett 2025; 36(07): 853-858
DOI: 10.1055/a-2417-1017
letter

Synthesis of 6-Hydroxy-8-chlorooctanoate Ethyl Ester by Chemoenzymatic Method

Zhengdong Ding
,
Hongbin Zhang∗
This research was supported by the Natural Science Foundation of Anhui Province (grant no. 2308085MC110). The authors are grateful to the Natural Science Foundation of Anhui Province for financial support.
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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

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/a-2417-1017.
  • Supporting Information


Publikationsverlauf

Eingereicht: 15. Juni 2024

Angenommen nach Revision: 17. September 2024

Accepted Manuscript online:
17. September 2024

Artikel online veröffentlicht:
14. Oktober 2024

© 2024. Thieme. All rights reserved

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