4033-27-6

Basic information

• Product Name: DIHYDROFOLIC ACID
• Synonyms: (S)-2-(4-(((2-aMino-4-oxo-1,4,7,8-tetrahydropteridin-6-yl)Methyl)aMino)benzaMido)pentanedioic acid;7,8-Dihydrofolic acid (DHF);Dihydrofolic acid 7,8-Dihydropteroyl-L-glutaMic acid;N-[4-[[(2-aMino-3,4,7,8-tetrahydro-4-oxo-6-pteridinyl)Methyl]aMino]benzoyl]-L-GlutaMic acid;Folinic Acid Impurity G (7,8-Dihydrofolic Acid);7,8-DIHYDROPTEROYL-L-GLUTAMIC ACID;FAH2;DIHYDROPTEROYL-L-GLUTAMIC ACID
• CAS NO: 4033-27-6
• Molecular Formula: C₁₉H₂₁N₇O₆
• Molecular Weight: 443.41
• Mol File: 4033-27-6.mol
• Article Data: 12

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: 1.69g/cm³
• Refractive Index: 1.762
• Storage Temp.: −20°C
• Solubility: 0.1 M NaOH: 10 mg/mL, slightly hazy, orange
• PKA: pKa 1.38(H2O t=25 I=0.10) (Occasionally);3.84(H2O t=25 I=0.10) (Occasionally)
• Stability: Air Sensitive, Hygroscopic, Temperature Sensitive
• BRN: 69017
• CAS DataBase Reference: DIHYDROFOLIC ACID(CAS DataBase Reference)
• NIST Chemistry Reference: DIHYDROFOLIC ACID(4033-27-6)
• EPA Substance Registry System: DIHYDROFOLIC ACID(4033-27-6)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• Hazardous Substances Data: 4033-27-6(Hazardous Substances Data)

Usage

Description

Dihydrofolic Acid (DHF) is an essential intermediate in the metabolic pathway that converts dietary folic acid to tetrahydrofolate (THF) in mammals. It plays a crucial role in various biochemical reactions, including the synthesis of nucleotides and amino acids. In bacteria, dihydrofolic acid is generated from 7,8-dihydropteroate by dihydrofolate synthetase. DHF is a vital compound for cellular function and growth.

Uses

1. Antidote to Methotrexate Toxicity:
Dihydrofolic Acid is used as an antidote for methotrexate toxicity, a condition that arises from the excessive accumulation of methotrexate in the body. Methotrexate is a drug that inhibits dihydrofolate reductase (DHFR), which is responsible for converting DHF to THF. By providing an alternative source of DHF, it helps to counteract the toxic effects of methotrexate.
2. Mammalian Metabolism:
Dihydrofolic Acid is used as an intermediate in the mammalian conversion of dietary folic acid to tetrahydrofolate by dihydrofolate reductase (DHFR). This process is essential for the synthesis of nucleotides, amino acids, and the maintenance of overall cellular function.
3. Bacterial Metabolism:
In the bacterial kingdom, Dihydrofolic Acid is used as a precursor in the generation of 7,8-dihydropteroate by dihydrofolate synthetase. DIHYDROFOLIC ACID is a crucial component in the bacterial metabolic pathway, contributing to the synthesis of essential biomolecules and cellular growth.

Biochem/physiol Actions

Folic acid (FA) and dihydrofolic acid (FAH2) are substrates of dihydrofolate reductase(s) which reduce them to tetrahydrofolate (THF), which in turn supports ‘one carbon′ transfer. Tetrahydrofolates are required for de novo synthesis of purines, thymidylic acid and various amino acids and for post-translational methylation (epigenetics).

Purification Methods

DHFA is best purified by suspending (1g mostly dissolved)) in ice-cold sodium ascorbate (300mL of 10% at pH 6.0, prepared by adjusting the pH of 30g of sodium ascorbate in 150mL of H2O by adding 1N NaOH dropwise using a gla

InChI:InChI=1/C19H21N7O6/c20-19-25-15-14(17(30)26-19)23-11(8-22-15)7-21-10-3-1-9(2-4-10)16(29)24-12(18(31)32)5-6-13(27)28/h1-4,12,21H,5-8H2,(H,24,29)(H,27,28)(H,31,32)(H4,20,22,25,26,30)/t12-/m0/s1

Upstream product

• 59-30-3 folic acid 
• 142811-51-6 N-<4-<<2(S)-amino-3-<(2,5-diamino-4(3H)-oxopyrimidin-6-yl)amino>propyl>amino>benzoyl>-L-glutamic acid 
• 4271-30-1 N-(4-aminobenzoyl)-L-glutamic acid 
• 3031-94-5 5-aminoimidazole-4-carboxamide ribonucleotide 
• 142811-49-2 N-<4-<<2(S)--3-<(2-amino-5-nitro-4(3H)-oxopyrimidin-6-yl)amino>propyl>amino>benzoyl>-L-glutamic acid 
• 142811-46-9 2-amino-6<<2'(R)-(benzylamino)-3'-hydroxypropyl>amino>-5-nitro-4(3H)-pyrimidinone 
• 142811-47-0 2-amino-6-<<2'(R)--3'-hydroxypropyl>amino>-5-nitro-4(3H)-pyrimidinone 
• 142811-48-1 [(R)-2-(2-Amino-5-nitro-6-oxo-1,6-dihydro-pyrimidin-4-ylamino)-1-formyl-ethyl]-benzyl-carbamic acid tert-butyl ester 
• 142811-50-5 N-<4-<<2(S)-(benzylamino)-3-<(2-amino-5-nitro-4(3H)-oxopyrimidin-6-yl)amino>propyl>amino>benzoyl>-L-glutamic acid 
• 2280-44-6 D-Glucose 
• 73-40-5 2-amino-1,9-dihydro-6H-purin-6-one 
• 86-01-1 Guanosine 5'-triphosphate 
• 1218-98-0 dihydro-7,8-D-neopterine 
• 3545-84-4 6-hydroxymethyl-7,8-dihydro-pterin pyrophosphate 

Downstream Products

• 135-16-0 (6S,S)-5,6,7,8-tetrahydrofolic acid 
• 71963-69-4 (6S,S)-5,6,7,8-tetrahydrofolic acid 
• 82949-83-5 5,10-bis(uracil-5-ylmethyl)tetrahydropteroylglutamic acid 
• 82883-89-4 5,10-bis(uracil-5-ylmethyl)<6-2H₁>tetrahydropteroylglutamic acid 
• 135-16-0 tetrahydrofolic acid 
• 74568-14-2 (7RS)-<7-(2)H1>-7,8-dihydrofolic acid 
• 135-16-0 (6-R,S)-5,6,7,8-tetrahydrofolate 
• 65981-90-0 (6R)-5,10-methylylidenetetrahydrofolic acid chloride 
• 58-05-9 folinic acid 
• 442634-22-2 5,10-methylidyne-5,6,7,8-tetrahydrofolic acid 
• 98814-61-0 (6RS,7RS)-<7-(2)H>-5-formyl-5,6,7,8-tetrahydrofolic acid 
• 59-30-3 folic acid 
• 1131-35-7 7,8-dihydroxanthopterin 
• 13214-44-3 6-formyl-7,8-dihydropterin 

Relevant articles and documents

A convenient synthesis of leucovorin

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Chemoenzymatic Assembly of Isotopically Labeled Folates

Pterin-containing natural products have diverse functions in life, but an efficient and easy scheme for their in vitro synthesis is not available. Here we report a chemoenzymatic 14-step, one-pot synthesis that can be used to generate 13C- and 15N-labeled dihydrofolates (H2F) from glucose, guanine, and p-aminobenzoyl-l-glutamic acid. This synthesis stands out from previous approaches to produce H2F in that the average yield of each step is >91% and it requires only a single purification step. The use of a one-pot reaction allowed us to overcome potential problems with individual steps during the synthesis. The availability of labeled dihydrofolates allowed the measurement of heavy-atom isotope effects for the reaction catalyzed by the drug target dihydrofolate reductase and established that protonation at N5 of H2F and hydride transfer to C6 occur in a stepwise mechanism. This chemoenzymatic pterin synthesis can be applied to the efficient production of other folates and a range of other natural compounds with applications in nutritional, medical, and cell-biological research.

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