Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Method for reacting L-5-methyltetrahydrofolic acid with organic base to form salt

A technology of calcium methyltetrahydrofolate and organic bases, applied in the directions of organic chemistry, chemical instruments and methods, amino sugars, etc., can solve problems such as poor stability and low yield, and achieve the effect of good stability

Inactive Publication Date: 2015-07-01
NAN JING RHINE PHARM TECH
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] Gnosis S.p.a. proposed the preparation method and application of L-5-methyltetrahydrofolate glucosamine salt and L-5-methyltetrahydrofolate galactosamine salt (US 7,947,662). In the preparation process of this method, the preparation (free Acid) L-5-methyltetrahydrofolate and (free base) glucosamine (D-Glucosamine) or galactose (D-Galactosamine), using water as a solvent for addition, the yield is low, the stability is poor, and special Equipment freeze drying or spray dryer

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for reacting L-5-methyltetrahydrofolic acid with organic base to form salt
  • Method for reacting L-5-methyltetrahydrofolic acid with organic base to form salt
  • Method for reacting L-5-methyltetrahydrofolic acid with organic base to form salt

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Under nitrogen flow, in a 1000ml three-necked flask, suspend 49.7g (0.1mol) of L-calcium tetrahydrofolate in 200ml of ethanol, and take another 43.1g (0.2mol) of glucosamine hydrochloride dissolved in 200ml of water. While stirring, slowly add to the ethanol suspension of L-calcium tetrahydrofolate, keeping the temperature at 0-20°C; stir the above mixture at room temperature for 8 hours, add dropwise 200ml of acetone or 300ml of absolute ethanol, and then stir for 6 hours; stand for 24 hours; filter, wash with cold ethanol / water, and dry under vacuum at 25-40°C. Recrystallize once if necessary. Obtained 61.8g of crystalline powder of L-5-methyltetrahydrofolate glutamine salt, yield 66.7%, chemical purity 98.6%, [α] 20 D =+54.1° (C=1, water) Optical purity ee≥99.0%.

Embodiment 2

[0028] Under nitrogen flow, in a 1000ml three-necked flask, suspend 49.7g (0.1mol) of L-calcium tetrahydrofolate in 300ml of ethanol, and take 454.5g (0.2mol) of glucosamine sulfuric acid dissolved in 300ml of water, while While stirring, slowly add to the ethanol suspension of L-calcium tetrahydrofolate, keeping the temperature at 20-30°C; stir the above mixture at room temperature for 2 hours, filter, remove calcium sulfate, add dropwise 200ml acetone or 300ml Absolute ethanol, stirring for another 6 hours; standing for 24 hours; filtering, washing with cold ethanol / water, and vacuum drying at 25-40°C. Recrystallize once if necessary. Obtained 62.6g of crystalline powder of L-5-methyltetrahydrofolate glutamine salt, yield 67.5%, chemical purity 98.5%, [α] 20 D =+53.9° (C=1, water) optical purity ee≥99.0%,.

Embodiment 3

[0030] Under nitrogen flow, in a 1000ml three-necked flask, suspend 49.7g (0.1mol) L-calcium tetrahydrofolate in 200ml ethanol, and take another 39.1g (0.2mol) N-methylglucose dissolved in 200ml water Sugar amine, while stirring, is slowly added to the ethanol suspension of L-methyltetrahydrofolate calcium, and the temperature is kept at 0-20°C; the above mixture is fully stirred at room temperature, and after 8 hours, 200ml of acetone or 300ml of anhydrous For ethanol, adjust the pH to 6.5 with dilute hydrochloric acid, and then stir for 6 hours; let stand for 24 hours; filter, wash with cold ethanol / water, and dry under vacuum at 25-40°C. Recrystallize once if necessary. Obtained 61.1 g of L-5-methyltetrahydrofolate meglumine salt crystalline powder, yield 68.9%, chemical purity 98.2%, [α] 20 D =+54.1° (C=1, water) Optical purity ee≥99.0%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a method for reacting L-5-methyltetrahydrofolic acid with an organic base to form a salt. The method comprises the following steps: allowing L-5-methyltetrahydrofolic acid to suspend in ethanol under nitrogen flow, and slowly adding a water-soluble hydrochloride or sulfate or a free base of the organic base to an obtained L-5-methyltetrahydrofolic acid ethanol suspension; fully mixing an obtained mixture, maintain the temperature in a range of 0-20DEG C, continuously stirring for 2h, adding acetone in a dropwise manner, and allowing an obtained mixture to stand for 24h; and filtering, washing with cold ethanol / water, and carrying out vacuum drying at 25-40DEG C.

Description

technical field [0001] The invention relates to the field of organic chemistry, in particular to a method for adding salts between an organic drug L-5-methyltetrahydrofolate and an organic base. Background technique [0002] The chemical name of L-5-methyltetrahydrofolate is N-(5-methyl)-6(S)-5,6,7,8,-tetrahydropteroyl-L-glutamic acid, referred to as L- 5-MTHF or (6S)-5-MTHF. L-5-methyltetrahydrofolate is the main form of folic acid in tissues and blood, and participates in many important biochemical reactions in the body (such as the biosynthesis of purine and thymine, etc.). The naturally occurring 5-MTHF is only in the L-form, while its chemically synthesized optical isomer D-form is inactive and excreted through the kidneys; L-5-MTHF does not require tedious enzymatic metabolism in the human body steps can be used directly. (Zhang Yue et al., Fine and Chemicals, 13, (22), 13, 2005). [0003] Earlier, L-5-MTHF has two important roles as a drug: in the treatment of onc...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D475/04C07H5/06C07H1/00
Inventor 陈新
Owner NAN JING RHINE PHARM TECH
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com