Flow Synthesis of L-α-Glycerylphosphorylcholine: Studies on Synthetic Routes Applicable to a Flow Reactor and Optimization of Reaction Conditions

L-α-Glycerylphosphorylcholine (L-α-GPC) has mainly been produced by two methods: extraction from plants rich in phosphatidylcholine and chemical synthesis. However, production through extraction involves difficult processes, such as fermentation, extractions and ripening, and conventional chemical s...

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Published in:Pharmaceutics 2022-11, Vol.14 (11), p.2480
Main Authors: Park, Jihun, Lee, Seungjae, Kim, Gyungtak, Malpani, Yashwardhan R, Park, Boyoung Y, Hwang, Ye-Jin
Format: Article
Language:English
Subjects:
Chemical properties
Chemicals
Chloride
Choline
Chromatography
flow chemistry
flow reactor
Glycerol
L-α-Glycerylphosphorylcholine
L-α-GPC
NMR
Nuclear magnetic resonance
phosphoryl choline
Potash
Potassium
Production costs
Sensors
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Summary:L-α-Glycerylphosphorylcholine (L-α-GPC) has mainly been produced by two methods: extraction from plants rich in phosphatidylcholine and chemical synthesis. However, production through extraction involves difficult processes, such as fermentation, extractions and ripening, and conventional chemical synthesis methods with high-cost reactants and a batch reactor. These methods are not ideal for large-quantity production. Thus, it is important to develop a simple production method of L-α-GPC, which is suitable for mass production without the need for expensive reactants. Here, we studied synthetic L-α-GPC methods that are applicable to a flow synthesis system, which can provide selectivity, reproducibility, scalability, and a high yield in short reaction time using inexpensive starting materials. We developed a two-step synthetic route to produce L-α-GPC, including the synthesis of phosphoryl choline using choline chloride and phosphoryl oxychloride (POCl ) as a first step and synthesis of L-α-GPC by reacting phosphoryl choline with ( )-(-)-3-chloro-1,2-propanediol (CPD) as a second step under basic conditions. Both steps were separately performed in a customized flow reactor, and reaction conditions were optimized. Finally, phosphoryl choline and L-α-GPC, the products first and second reactions, were successfully synthesized with high conversion yields of 97% and 79%, respectively.
ISSN:1999-4923
1999-4923
DOI:10.3390/pharmaceutics14112480