Record Information
Version 1.0
Update Date 1/22/2018 11:54:54 AM
Metabolite IDPAMDB120482
Identification
Name: 5-formyl-tetrahydrofolate
Description:A dicarboxylic acid dianion arising from deprotonation of both carboxylic acid groups of (6S)-5-formyltetrahydrofolic acid.
Structure
Thumb
Synonyms:
  • 5-formyltetrahydrofolate
  • 5-formyltetrahydrofolate dianion
Chemical Formula: C20H21N7O7
Average Molecular Weight: 471.429
Monoisotopic Molecular Weight: 473.1659
InChI Key: VVIAGPKUTFNRDU-STQMWFEESA-L
InChI:InChI=1S/C20H23N7O7/c21-20-25-16-15(18(32)26-20)27(9-28)12(8-23-16)7-22-11-3-1-10(2-4-11)17(31)24-13(19(33)34)5-6-14(29)30/h1-4,9,12-13,22H,5-8H2,(H,24,31)(H,29,30)(H,33,34)(H4,21,23,25,26,32)/p-2/t12-,13-/m0/s1
CAS number: 58-05-9
IUPAC Name:N-[4-({[(6S)-2-amino-5-formyl-4-oxo-3,4,5,6,7,8-hexahydropteridin-6-yl]methyl}amino)benzoyl]-L-glutamate
Traditional IUPAC Name: 2-[(4-{[(2-amino-5-formyl-4-oxo-3,6,7,8-tetrahydropteridin-6-yl)methyl]amino}phenyl)formamido]pentanedioic acid
SMILES:C(NC1(C=CC(C(=O)NC(C(=O)[O-])CCC([O-])=O)=CC=1))[CH]3(CNC2(=C(C(=O)NC(N)=N2)N([CH]=O)3))
Chemical Taxonomy
Taxonomy DescriptionThis compound belongs to the class of chemical entities known as tetrahydrofolic acids. These are heterocyclic compounds based on the 5,6,7,8-tetrahydropteroic acid skeleton conjugated with at least one L-glutamic acid unit.
Kingdom Chemical entities
Super ClassOrganic compounds
Class Organoheterocyclic compounds
Sub ClassPteridines and derivatives
Direct Parent Tetrahydrofolic acids
Alternative Parents
Substituents
  • Tetrahydrofolic acid
  • Glutamic acid or derivatives
  • Hippuric acid or derivatives
  • Hippuric acid
  • N-acyl-alpha amino acid or derivatives
  • N-acyl-alpha-amino acid
  • Alpha-amino acid or derivatives
  • Aminobenzamide
  • Aminobenzoic acid or derivatives
  • Benzamide
  • Benzoic acid or derivatives
  • Benzoyl
  • Phenylalkylamine
  • Aniline or substituted anilines
  • Aminopyrimidine
  • Secondary aliphatic/aromatic amine
  • Pyrimidone
  • Dicarboxylic acid or derivatives
  • Monocyclic benzene moiety
  • Primary aromatic amine
  • Benzenoid
  • Pyrimidine
  • Heteroaromatic compound
  • Vinylogous amide
  • Tertiary carboxylic acid amide
  • Amino acid
  • Amino acid or derivatives
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Carboxylic acid
  • Carboxylic acid derivative
  • Secondary amine
  • Azacycle
  • Organic nitrogen compound
  • Carbonyl group
  • Organonitrogen compound
  • Organooxygen compound
  • Primary amine
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular Framework Aromatic heteropolycyclic compounds
External Descriptors Not Available
Physical Properties
State: Solid
Charge:-2
Melting point: Not Available
Experimental Properties:
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.3 mg/mLALOGPS
logP-0.46ALOGPS
logP-3.4ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.18ChemAxon
pKa (Strongest Basic)4.33ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count11ChemAxon
Hydrogen Donor Count7ChemAxon
Polar Surface Area215.55 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity126.66 m3·mol-1ChemAxon
Polarizability46.59 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations: Not Available
Reactions:
Pathways:
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0031900000-31498c227b611f3360eaView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6r-0393400000-f81606ae4f4b27aadbacView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4i-1591000000-825bc8196995ef0bc1e3View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0000900000-203ae236b032df3233d7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0umj-1131900000-5174748fd5288f6523fdView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0007-9674000000-192da85bfca095ec870eView in MoNA
References
References:
  • Perry TL, Applegarth DA, Evans ME, Hansen S, Jellum E: Metabolic studies of a family with massive formiminoglutamic aciduria. Pediatr Res. 1975 Mar;9(3):117-22. [235753 ]
  • Garbis SD, Melse-Boonstra A, West CE, van Breemen RB: Determination of folates in human plasma using hydrophilic interaction chromatography-tandem mass spectrometry. Anal Chem. 2001 Nov 15;73(22):5358-64. [11816560 ]
  • Straw JA, Szapary D, Wynn WT: Pharmacokinetics of the diastereoisomers of leucovorin after intravenous and oral administration to normal subjects. Cancer Res. 1984 Jul;44(7):3114-9. [6609768 ]
  • Micke O, Bruns F, Schafer U, Kurowski R, Horst E, Willich N: CA 19-9 in the therapy monitoring and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy. Anticancer Res. 2003 Mar-Apr;23(2A):835-40. [12820309 ]
  • Pfeiffer CM, Fazili Z, McCoy L, Zhang M, Gunter EW: Determination of folate vitamers in human serum by stable-isotope-dilution tandem mass spectrometry and comparison with radioassay and microbiologic assay. Clin Chem. 2004 Feb;50(2):423-32. Epub 2003 Dec 11. [14670827 ]
  • Karakayali FY, Bayar S, Hazinedaroglu S, Sahin F, Karayalcin K: Does folinic acid have a choleretic effect on humans? Turk J Gastroenterol. 2003 Jun;14(2):102-5. [14614635 ]
  • Pineda M, Ormazabal A, Lopez-Gallardo E, Nascimento A, Solano A, Herrero MD, Vilaseca MA, Briones P, Ibanez L, Montoya J, Artuch R: Cerebral folate deficiency and leukoencephalopathy caused by a mitochondrial DNA deletion. Ann Neurol. 2006 Feb;59(2):394-8. [16365882 ]
  • Birmingham BK, Greene DS: Analysis of folinic acid in human serum using high-performance liquid chromatography with amperometric detection. J Pharm Sci. 1983 Nov;72(11):1306-9. [6606033 ]
  • Sengelov L, von der Maase H, Lundbeck F, Barlebo H, Colstrup H, Engelholm SA, Krarup T, Madsen EL, Meyhoff HH, Mommsen S, Nielsen OS, Pedersen D, Steven K, Sorensen B: Neoadjuvant chemotherapy with cisplatin and methotrexate in patients with muscle-invasive bladder tumours. Acta Oncol. 2002;41(5):447-56. [12442921 ]
  • Bunni MA, Priest DG: Human red blood cell-mediated metabolism of leucovorin [(R,S)5-formyltetrahydrofolate] Arch Biochem Biophys. 1991 May 1;286(2):633-7. [1897982 ]
  • Ramaekers VT, Hausler M, Opladen T, Heimann G, Blau N: Psychomotor retardation, spastic paraplegia, cerebellar ataxia and dyskinesia associated with low 5-methyltetrahydrofolate in cerebrospinal fluid: a novel neurometabolic condition responding to folinic acid substitution. Neuropediatrics. 2002 Dec;33(6):301-8. [12571785 ]
  • Zhu WY, Alliegro MA, Melera PW: The rate of folate receptor alpha (FR alpha) synthesis in folate depleted CHL cells is regulated by a translational mechanism sensitive to media folate levels, while stable overexpression of its mRNA is mediated by gene amplification and an increase in transcript half-life. J Cell Biochem. 2001 Mar 26;81(2):205-19. [11241661 ]
  • Jansman FG, Coenen JL, De Graaf JC, Tobi H, Sleijfer DT, Brouwers JR: Relationship between pharmacokinetics of 5-FU in plasma and in saliva, and toxicity of 5-fluorouracil/folinic acid. Anticancer Res. 2002 Nov-Dec;22(6B):3449-55. [12552938 ]
  • Vimercati A, Greco P, D'Apolito A, Angelici MC, Possenti A, Carbonara S, Selvaggi L: [Risk assessment of vertical transmission of Toxoplasma infections] Acta Biomed Ateneo Parmense. 2000;71 Suppl 1:537-40. [11424802 ]
  • Joulia JM, Pinguet F, Ychou M, Duffour J, Astre C, Bressolle F: Plasma and salivary pharmacokinetics of 5-fluorouracil (5-FU) in patients with metastatic colorectal cancer receiving 5-FU bolus plus continuous infusion with high-dose folinic acid. Eur J Cancer. 1999 Feb;35(2):296-301. [10448274 ]
  • Polyzos A, Kouraklis G, Giannopoulos A, Bramis J, Delladetsima JK, Sfikakis PP: Irinotecan as salvage chemotherapy for advanced small bowel adenocarcinoma: a series of three patients. J Chemother. 2003 Oct;15(5):503-6. [14598944 ]
  • Micke O, Hesselmann S, Bruns F, Horst E, Devries A, Schuller P, Willich N, Schafer U: Results and follow-up of locally advanced cancer of the exocrine pancreas treated with radiochemotherapy. Anticancer Res. 2005 May-Jun;25(3A):1523-30. [16033054 ]
  • Bentivoglio G, Melica F, Cristoforoni P: Folinic acid in the treatment of human male infertility. Fertil Steril. 1993 Oct;60(4):698-701. [8405528 ]
  • Kajiyama Y, Tsurumaru M, Udagawa H, Tsutsumi K, Kinoshita Y, Akiyama H: Relief of jaundice by 5-fluorouracil and folinic acid in patients with recurrent gastric cancer. Surg Oncol. 1996 Aug;5(4):177-81. [9067566 ]
  • Jardine LF, Ingram LC, Bleyer WA: Intrathecal leucovorin after intrathecal methotrexate overdose. J Pediatr Hematol Oncol. 1996 Aug;18(3):302-4. [8689347 ]
Synthesis Reference: Zakrzewski, Sigmund F.; Sansone, Annette M. Preparation of folinic acid (N5-formyltetrahydro folic acid). Methods Enzymol. (1971), 18(Pt. B), 731-3.
Material Safety Data Sheet (MSDS) Not Available
External Links:
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METABOLIGHTSMTBLC57457
HMDBHMDB01562
CHEMSPIDER5028014
CHEBI57457
PUBCHEM6560146
LIGAND-CPDC03479
CAS58-05-9