Lipase-Catalyzed Dynamic Combinatorial Resolution and the Synthesis of Heteroaromatic Cyanohydrin Ester Enantiomers

Five structurally related thiophene-based aldehydes, acetone cyanohydrin, a base, a lipase enzyme and isopropenyl acetate have been mixed in one-pot, leading to the dynamic combinatorial resolution of a cyanohydrin library. The process is applied in optimizing synthetic conditions for the cyanohydri...

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Bibliographic Details
Main Authors: Sundell R, Kanerva LT, Turcu MC
Other Authors: PÄÄT Farmakologia lääkekehitys ja lääkehoito, PÄÄT Farmakologia lääkekehitys ja lääkehoito, 2607102
Language:English
Published: BENTHAM SCIENCE PUBL LTD 2022
Subjects:
Antarc*
Antarctica
Online Access:https://www.utupub.fi/handle/10024/170650
Description
Summary:Five structurally related thiophene-based aldehydes, acetone cyanohydrin, a base, a lipase enzyme and isopropenyl acetate have been mixed in one-pot, leading to the dynamic combinatorial resolution of a cyanohydrin library. The process is applied in optimizing synthetic conditions for the cyanohydrin acetate library obtained in terms of reactivity and enantiopurity. Anhydrous Na2CO3 and lipase PS-D (Burkholderia cepacia lipase) or Novozym 435 (Candida antarctica lipase B) preparations are shown to be the best catalyst combinations for the DCR of the substrate series in toluene. The justification of the optimized process is confirmed by preparing the thiophene -based (R)-cyanohydrin acetates with 68-99% isolated yields and 82-91 % ee using the traditional dynamic kinetic resolution of each substrate.

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