Citation: Liming Cao, Maolin Sun, Chaoming Liang, Lei Yang, Yueyue Ma, Ruihua Cheng, Yanxiong Ke, Wei Yu, Jinxing Ye. A sequential continuous flow synthesis and purification process of calcium dibutyryladenosine cyclophosphate[J]. Chinese Chemical Letters, ;2024, 35(2): 108758. doi: 10.1016/j.cclet.2023.108758 shu

A sequential continuous flow synthesis and purification process of calcium dibutyryladenosine cyclophosphate

Liming Cao ^a ,
Maolin Sun ^{b, *,} ,
Chaoming Liang ^b ,
Lei Yang ^a ,
Yueyue Ma ^b ,
Ruihua Cheng ^b ,
Yanxiong Ke ^{a, *,} ,
Wei Yu ^{a, c} ,
Jinxing Ye ^{a, b, *,}

a.
Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China
b.
School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
c.
Shanghai No.1 Biochemical & Pharmaceutical Co., Ltd., Shanghai 200080, China

maolinsun@gdut.edu.cn

key@ecust.edu.cn

yejx@ecust.edu.cn

jinxingye@gdut.edu.cn

Received Date: 12 May 2023
Revised Date: 21 June 2023
Accepted Date: 29 June 2023
Available Online: 1 July 2023

Figures(6)

Calcium dibutyryladenosine cyclophosphate is a widely used cardiovascular drug. The traditional batch synthesis process suffers from long reaction times, tedious operations, and unstable yields. Herein, a sequential continuous flow synthesis combined with a multistage in-line purification process of calcium dibutyryladenosine cyclophosphate was developed. The acylation reaction was completed in a continuous coil reactor at 160 ℃ in 20 min. And the high toxic solvent pyridine was replaced by acetonitrile. Furthermore, the multistage in-line purification process was integrated into the homemade 3D circular cyclone-type micromixer chip. Combining with the membrane phase separators, the residence time of the purification step was 30 s. The isolated yield of this sequential continuous process was 92% with 99% purity.
- Flow chemistry,
- Calcium dibutyryladenosine cyclophosphate,
- Continuous flow synthesis,
- In-line purification,
- 3D circular cyclone-type micromixer chip
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