Practical synthesis of tetrahydrofolate by highly efficient catalytic hydrogenation in continuous flow

IF 2 4区化学 Q3 CHEMISTRY, MULTIDISCIPLINARY

Journal of Flow Chemistry Pub Date : 2024-02-16 DOI:10.1007/s41981-024-00310-7

Heng Pang, Junrong Huang, Juntao Wang, Gang Wang, Ana Xu, Lei Luo, Qunhui Yuan, Hengzhi You, Fen-Er Chen

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Abstract

Hundred-gram scale of highly selective catalytic hydrogenation of folic acid has been developed, which is adopted continuous-flow technology with Raney Ni as a catalyst. Through optimization of the reaction condition, a high conversion rate of folic acid (> 99%) and a high selectivity (99%) of tetrahydrofolate have been achieved. Additionally, a high-purity calcium-6S-5-methyltetrahydrofolate (6S-5-MTHF.Ca) has been synthesized from tetrahydrofolate obtained by continuous hydrogenation through chiral resolution, methylation, salting and recrystallization (purity: 99.5%, de: 97.6%). Compared to known methods, this method provides a feasible procedure using simple, inexpensive, and readily available reagents, making it a step-economical and cost-effective alternative strategy for production of tetrahydrofolate and its active derivatives.

Graphical Abstract

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通过连续流高效催化加氢法合成四氢叶酸的实用方法

采用连续流技术，以 Raney Ni 为催化剂，开发了百克级叶酸高选择性催化加氢反应。通过优化反应条件，实现了叶酸的高转化率（99%）和四氢叶酸的高选择性（99%）。此外，通过手性解析、甲基化、盐析和重结晶，从连续氢化得到的四氢叶酸合成了高纯度的 6S-5-MTHF.Ca (纯度：99.5%，de：97.6%)。与已知方法相比，该方法使用简单、廉价和容易获得的试剂，提供了一个可行的程序，使其成为生产四氢叶酸及其活性衍生物的一种步骤经济、成本效益高的替代策略。

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来源期刊

Journal of Flow Chemistry CHEMISTRY, MULTIDISCIPLINARY-

CiteScore

6.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： The main focus of the journal is flow chemistry in inorganic, organic, analytical and process chemistry in the academic research as well as in applied research and development in the pharmaceutical, agrochemical, fine-chemical, petro- chemical, fragrance industry.