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. 2024 Apr 4;14(16):10953-10961.
doi: 10.1039/d4ra00097h. eCollection 2024 Apr 3.

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus

Shi-Yi Zhang  1 , Guo-Neng Fu  1 , Li-Hua Du  1 , Hang Lin  1 , Ao-Ying Zhang  1 , Han-Jia Xie  1 , Zhi-Kai Sheng  1 , Miao-Miao Xue  1 , Bing-Lin Yan  1 , Yi Liu  1 , Zhi-Xuan Ruan  1 , Bing-Le Pan  1 , Tong-Yao Zhou  1 , Xi-Ping Luo  2
Affiliations

Continuous flow biocatalysis: synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus

Shi-Yi Zhang et al. RSC Adv. .

Abstract

Purine nucleoside ester is one of the derivatives of purine nucleoside, which has antiviral and anticancer activities. In this work, a continuous flow synthesis of purine nucleoside esters catalyzed by lipase TL IM from Thermomyces lanuginosus was successfully achieved. Various parameters including solvent, reaction temperature, reaction time/flow rate and substrate ratio were investigated. The best yields were obtained with a continuous flow microreactor for 35 min at 50 °C with the substrate ratio of 1 : 5 (nucleosides to vinyl esters) in the solvent of tert-amyl alcohol. 12 products were efficiently synthesized with yields of 78-93%. Here we reported for the first time the use of lipase TL IM from Thermomyces lanuginosus in the synthesis of purine nucleoside esters. The significant advantages of this methodology are a green solvent and mild conditions, a simple work-up procedure and the highly reusable biocatalyst. This research provides a new technique for rapid synthesis of anticancer and antiviral nucleoside drugs and is helpful for further screening of drug activity.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Scheme 1
Scheme 1. Synthesis and design of purine nucleoside esters catalyzed by lipase TL IM in continuous-flow microreactors.
Fig. 1
Fig. 1. The influence of substrate ratio (adenosine: vinyl laurate) on the synthesis of adenosine laurate ester catalyzed by lipase TL IM in continuous-flow microreactors.
Fig. 2
Fig. 2. The influence of reaction temperature on the synthesis of adenosine laurate ester catalyzed by lipase TL IM in continuous-flow microreactors.
Fig. 3
Fig. 3. The influence of residence time on the synthesis of adenosine laurate ester catalyzed by lipase TL IM in continuous-flow microreactors.
Fig. 4
Fig. 4. The influence of number of repeated reaction on the synthesis of adenosine laurate ester catalyzed by lipase TL IM in continuous-flow microreactors.
Fig. 5
Fig. 5. The effect of different kinds of vinyl esters on the synthesis of adenosine laurate ester catalyzed by lipase TL IM in continuous-flow microreactors.
Fig. 6
Fig. 6. The effect of different kinds of purine nucleosides on the synthesis of adenosine laurate ester catalyzed by lipase TL IM in continuous-flow microreactors.
Fig. 7
Fig. 7. Equipment for the enzymatic synthesis of purine nucleoside esters in continuous-flow microreactors.
See this image and copyright information in PMC

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