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Resolution for 5-methyltetrahydrofolic acid and salifying method thereof

A technology of methyltetrahydrofolate and calcium methyltetrahydrofolate, which is applied in the directions of organic chemical methods, chemical instruments and methods, separation of optically active compounds, etc., can solve restrictions, chloride ions do not meet the limit inspection of chloride ions, and the market price is relatively low. Expensive and other issues

Inactive Publication Date: 2010-08-11
NAN JING RHINE PHARM TECH
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Problems solved by technology

And Klaus.S et al. have proposed the organic base N-ethyl-2-aminomethylpyrrolidine or its enantiomer as a resolution agent from the racemate (6R, S)-5-methyl The method for preparing (6S)-5-methyltetrahydrofolate from tetrahydrofolate (U.S 5,457,202, 1992) created a precedent for the resolution of (6R, S)-5-MTHF, but due to N-ethyl-2-amine Especially (+) or (-) enantiomeric market price of methylpyrrole is more expensive, has limited its application; Some documents used calcium chloride (Fedrico G, et al, U.S 5,124,452, 1992), and finally in the product (6S)-5-MTHF-Ca, a large amount of chloride ions are likely to remain in the product (6S)-5-MTHF-Ca, resulting in the inspection of the chloride ion limit that does not meet the requirements of drugs or food additives

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  • Resolution for 5-methyltetrahydrofolic acid and salifying method thereof

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Abstract

The invention brings forward a preparation method, which utilizes organic alkali Alpha-phenylethylamine to obtain (6S)-5-methyltetrahydrofolate by splitting racemate (6R, S)-5-methyltetrahydrofolate, and utilizes the hydroxide of alkaline earth, particularly calcium hydroxide, to generate (6S)-5-methyltetrahydrofolate calcium salt.

Description

Invention field The present invention relates to the field of organic chemistry, in particular to a method for the resolution and salt formation of organic medicine (6S)-5-methyltetrahydrofolate from (6R,S)-5-methyltetrahydrofolate. Background technique The chemical name of (6S)-5-methyltetrahydrofolate is N-(5-methyl)-6(S)-5,6,7,8,-tetrahydropteroyl-L-glutamic acid, abbreviated (6S)-5-MTHF, the structural formula is as follows: (6S)-5-Methyltetrahydrofolate is the main form of tissue and blood folic acid. Participate in a variety of important biochemical reactions in the body (such as purine and thymine biosynthesis, etc.). The naturally occurring 5-MTHF is only the S type, while the synthetic R type is biochemically inactive and is excreted through the kidneys. (6S)-5-MTHF does not need to go through tedious enzymatic metabolism steps in the human body and can be used directly. (Zhang Yue et al. Fine Chemicals, 13, (22), 13, 2005). Earlier, (6S)-5-MTHF as a drug has two ...

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D475/04C07B57/00
CPCC07D475/04
Inventor 陈新朱光旭陈伟
Owner NAN JING RHINE PHARM TECH
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