31690-09-2

Basic information

• Product Name: Levomefolic Acid
• Synonyms: (6S)-5-Methyltetrahydrofolic acid;5lLCH3-folateH4;L(-)-5-Methyl-5,6,7,8-tetrahydrofolic acid;lL-5-Methyltetrahydrofolic acid;N-[4-[[[(6S)-2-Amino-5-methyl-1,4,5,6,7,8-hexahydro-4-oxopteridine-6-yl]methyl]amino]benzoyl]-L-glutamic acid;N-[4-[[[[(6S)-2-Amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxopteridin]-6-yl]methyl]amino]benzoyl]-L-glutamic acid;(S)-N-[4-[[(2-Amino-1,4,5,6,7,8-hexahydro-5-methyl-4-oxo-6-pteridinyl)methyl]amino]benzoyl]-L-glutamic acid;Levomefolic acid
• CAS NO: 31690-09-2
• Molecular Formula: C₂₀H₂₅N₇O₆
• Molecular Weight: 459.46
• Product Categories: Amines;Aromatics;Drug Analogues;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 31690-09-2.mol

Chemical Properties

• Appearance: /
• Density: 1.62
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Aqueous Base (Slightly, Heated, Sonicated), DMSO (Slightly)
• PKA: 3.51±0.10(Predicted)
• CAS DataBase Reference: Levomefolic Acid(CAS DataBase Reference)
• NIST Chemistry Reference: Levomefolic Acid(31690-09-2)
• EPA Substance Registry System: Levomefolic Acid(31690-09-2)

Safety Data

• Hazardous Substances Data: 31690-09-2(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
Levomefolic Acid is used as a dietary supplement for its bioavailability and ability to support various cellular functions, including DNA reproduction, the cysteine cycle, and homocysteine regulation.
Used in Cardiovascular Disease Treatment:
Levomefolic Acid is used as a therapeutic agent for the treatment of cardiovascular disease, potentially offering benefits in managing and preventing related health issues.

Mechanism

It is synthesized in the absorptive cells of the small intestine from polyglutamylated dietary folate. It is a methylated derivative of tetrahydrofolate. Levomefolic acid is generated by methylenetetrahydrofolate reductase (MTHFR) from 5,10-methylenetetrahydrofolate (MTHF) and used to recycle homocysteine back to methionine by methionine synthase (MS).

Medical application

Levomefolic acid (5-MTHF) is the natural, active form of folic acid used at the cellular level for DNA reproduction, the cysteine cycle and the regulation of homocysteine among other functions. IC50 value: Target: Folate analogLevomefolic acid has been proposed for treatment of cardiovascular disease and advanced cancers such as breast and colorectal cancers. Levomefolic acid (5-MTHF) has the prominent antioxidant activity. A high dose of 5-MTHF or folic acid does not influence Natural killer (NK) cell function in vitro. Preliminary research suggests that levomefolic acid (L-methylfolate) taken with a first-line antidepressant may provide an adjunctive antidepressant effect for individuals who do not respond or have only a partial therapeutic response to SSRI or SNRI medication,and might be a more cost-effective adjunctive agent than second-generation antipsychotics.

Storage

Store lyophilized at -20oC, keep desiccated.In lyophilized form, the chemical is stable for 36 months.In solution, store at -20oC and use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Upstream product

• 59-30-3 folate 
• 50-00-0 formaldehyd 
• 1336-21-6 ammonium hydroxide 
• 135-16-0 (6S,S)-5,6,7,8-tetrahydrofolic acid 
• 31690-11-6 N⁵,N¹⁰-methylenetetrahydrofolate 

Relevant articles and documents

Process for preparing L-5 - methyl tetrahydrofolinate

The invention relates to a preparation process of L-5 - methyl tetrahydrofolic acid, which adopts asymmetric catalytic hydrogenation to convert folic acid into (6S) - tetrahydro folic acid, and has high folic acid conversion rate, and (6S) - tetrahydrofolic acid diastereomeric excess degree. By salt formation and crystallization, the (6S) - tetrahydrofolic acid intermediate with extremely high diastereomeric excess can be easily enriched, and thus the yield and purity of L-5 - methyltetrahydrofolinate finally obtained are high. The catalytic hydrogenation process is very mature in industrial application and convenient to operate. The subsequent methylation and salt formation steps are easy to implement, and the preparation process has high economic value and practical value under the condition that the yield and purity of the product are improved.

Preparation method of L-5-calcium methyltetrahydrofolate

The invention discloses a preparation method of L-5-calcium methyltetrahydrofolate. The preparation method comprises the following steps of (1) adopting folic acid as a raw material, and reducing to preparing an intermediate 6-(R,S)-tetrahydrofolic acid; (2) carrying out chiral resolution on the 6-(R,S)-tetrahydrofolic acid, and obtaining an intermediate 6-S-tetrahydrofolate; (3) carrying out methylation on the 6-S-tetrahydrofolate to obtain an intermediate L-5-methyltetrahydrofolate; (4) reacting the L-5-methyltetrahydrofolate and salt containing calcium to obtain the L-5-calcium methyltetrahydrofolate. According to the method provided by the invention, the problem that hydrogen, wastewater and waste residues are easily generated by using a large number of sodium borohydride is avoided.

Synthesis of (6S)-5,6,7,8-tetrahydrofolic acid

A process for the large-scale chemoenzymatic production of (6S)-5-methyl-5,6,7,8-tetrahydrofolic acid, also known as (6S)-5-methylTHFA, the process comprising the steps of: (1) reducing folic acid (FA) so as to yield dihydrofolic acid (DHFA); (2) stereoselectively reducing DHFA with dihydrofolate reductase (DHFR) in the presence of NADP/NADPH, glucose and GluDH so as to yield (6S)-THFA; (3) converting (6S)-THFA to (6S)-5-methlTHFA; and (4) isolating (6S)-5-methylTHFA.

RESOLUTION OF TETRAHYDROFOLIC ACID DERIVATIVES

A process of preparing (6S)-tetrahydrofolic acid derivatives comprising reacting racemic (6RS)-tetrahydrofolic acid derivatives with N-alkyl-D-glucamine, forming N-alkyl-D-glucamine salts of the (6RS)-tetrahydrofolic acid derivatives, isolation of the N-alkyl-D-glucamine salt of the (6S)-tetrahydrofolic acid derivative, removal of the N-alkyl-D-glucamine cation and purification of the (6S)-tetrahydrofolic acid derivative. The purified (6S)-tetrahydrofolic acid derivative can then be converted into the corresponding alkali metal or alkaline earth metal salts.

A PROCESS FOR THE PREPARATION OF THE STABLE, AMORPHOUS CALCIUM SALT OF (6S)-N(5)-METHYL-5,6,7,8-TETRAHYDROFOLIC ACID

A process for the preparation of an aqueous solution of the calcium salt of (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid, whereby (6S)-5,6,7,8-tetrahydrofolic acid having a content of the corresponding (6R)-diastereoisomer in the range from 4% by weight to 8% by weight is methylated in water comprises: treating the methylated reaction mixture with calcium chloride; crystallizing the calcium salt of (6RS)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid from the resulting aqueous solution; and obtaining an aqueous solution of the calcium salt of (6S)-N(5)-methyl-5,6,7,8-tetrahydrofolic acid.