69056-38-8

Basic information

• Product Name: (6R)-5,6,7,8-TETRAHYDRO-L-BIOPTERIN DIHYDROCHLORIDE
• Synonyms: (6r-(6r*(1r*,2s*)))-chlorid;(6r)-tetrahydrobiopterinhydrochloride;5,6,7,8-tetrahydro-2-amino-6-(1,2-dihydroxypropyl)-4(1h)-pteridinondihydro;sapropterinhydrochloride;sun0588;6R-BH4;(6R)-BH4 2HCL;[6R-[6R*(1R*,2S*)]]-2-AMINO-6-(1,2-DIHYDROXY-PROPYL)-5,6,7,8-TETRAHYDRO-4(1H)-PTERIDINONE DIHYDROCHLORIDE
• CAS NO: 69056-38-8
• Molecular Formula: C₉H₁₅N₅O₃*2ClH
• Molecular Weight: 314.17
• EINECS: 1308068-626-2
• Product Categories: Chemical Amines;Amines;Chiral Reagents;Heterocycles;Nitric Oxide Reagents;Nitric Oxide
• Mol File: 69056-38-8.mol
• Article Data: 7

Chemical Properties

• Melting Point: 245-246° (dec)
• Boiling Point: 506.6 °C at 760 mmHg
• Flash Point: 260.2 °C
• Appearance: white crystalline solid
• Vapor Pressure: 2.2E-12mmHg at 25°C
• Storage Temp.: −20°C
• Solubility: water, oxygen free: soluble19.60 - 20.40mg/mL, clear to slightly
• CAS DataBase Reference: (6R)-5,6,7,8-TETRAHYDRO-L-BIOPTERIN DIHYDROCHLORIDE(CAS DataBase Reference)
• NIST Chemistry Reference: (6R)-5,6,7,8-TETRAHYDRO-L-BIOPTERIN DIHYDROCHLORIDE(69056-38-8)
• EPA Substance Registry System: (6R)-5,6,7,8-TETRAHYDRO-L-BIOPTERIN DIHYDROCHLORIDE(69056-38-8)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: UO3516500
• Hazardous Substances Data: 69056-38-8(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 69056-38-8 differently. You can refer to the following data:
1. Sapropterin hydrochloride is a monoamine biosynthesis enhancer introduced for the treatment of hyperphenylalaninemia.Animal studies indicate that sapropterin hydrochloride increases brain levels of serotonin and enhances the release of acetylcholine from nerve terminals. The compound is also being investigated as a potential cognitive enhancer.
2. (6R)-5,6,7,8-tetrahydro-L-Biopterin (hydrochloride) (BH4) is a cofactor that, in the presence of enzyme site iron, binds to phenylalanine hydroxylase, tryptophan or tyrosine hydroxylase, and nitric oxide synthase (NOS), to facilitate the production of aromatic amino acids, neurotransmitters, and nitric oxide (NO), respectively. It is formed de novo from GTP with GTP cyclohydrolase-1 (GCH1) catalyzing the rate limiting conversion of GTP to 7,8-dihydroneopterin (NH2TP) followed by subsequent processing by TS and SPR to convert NH2TP to BH4. BH4 acts as a radical-trapping antioxidant that inhibits phospholipid oxidation in lipid membranes. It inhibits IKE- or RSL3-induced ferroptosis in HT-1080 cells (EC50s = 21 and 69 μM), as well as ferroptosis induced by knockout of glutathione peroxidase (Gpx4-/-) in immortalized mouse fibroblasts. BH4 also reduces RLS3-induced lipid peroxidation in murine fibroblasts and HT-1080 cells when used at a concentration of 50 μM.

Chemical Properties

White Crystalline Solid

Originator

Suntory (Japan)

Definition

ChEBI: The dihydrochloride salt of sapropterin. It is used for the diagnosis and treatment of variant forms of phenylketonuria (hyperphenylalaninaemia) associated with tetrahydrobiopterin deficiency. Natural cofactor for phenylalanine hydroxylase, tyrosine hydrox lase, tryptophan hydroxylase, and nitric oxide synthetase.

Brand name

Biopten

General Description

Tetrahydrobiopterin is a natural cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase, nitric oxide synthase and alkylglycerol monooxygenase.

Biochem/physiol Actions

Lack of tetrahydrobiopterin may cause hyperphenylalaninemia. Diseases like, Parkinson′s, autism, depression and Alzheimer′s shows low concentration of tetrahydrobiopterin in the cerebrospinal fluid. This coenzyme participates in dopamine (DA) synthesis.

Purification Methods

Recrystallisation of BH4.2HCl from HCl enriches BH4 in the natural 6R isomer. Dissolve the salt (~6g) in conc HCl (15mL) under gentle warming, then add EtOH (30mL) dropwise, chill and collect the colourless needles (67%, up to 99% if the mother liquors are concentrated), and dry it in vacuo immediately over P2O5 and KOH. It is stable indefinitely at -20o in a dry atmosphere. Better store it in sealed ampoules under dry N2. It can be recrystallised from 6N aqueous HCl. It has UV max (in 2N HCl) at 264nm ( 16,770; pH 3.5 phosphate buffer) 265nm ( 13,900); (in pH 7.6) at 297nm ( 9,500) and 260nm sh ( 4,690). It has been separated from the 6S-isomer by HPLC on a Partisil-10SCX column using 30mM ammonium phosphate buffer (pH 3.0) containing 3mM NaHSO3 (2mL/minute flow rate; 275nm detector) with retention times of 5.87minutes (6R) and 8.45minutes (6S). It is stable in acidic solutions and can be stored for extended periods at -20o in 0.04M HCl. Above pH 7 the neutral species are obtained, and these are readily oxidised by the oxygen in the solvent to the quinonoid species, and then further oxidation and degradation occurs at room temperature. These changes are slower at 0o. The sulfate salt can be obtained by recrystallisation from 2M H2SO4 and is less soluble in water than the hydrochloride salt. The 6R-2,5,1',2'-tetraacetylbiopterin derivative has m 292o(dec) after recrystallisation from MeOH (100 parts) and [] 20 -144o (c 0.5, CHCl3), [] 589 +12.8o (c 0.39, Me2SO). [NMR, UV: Matsuura et al. Heterocycles 23 3115 1985, Viscontini et al. Helv Chim Acta 62 2577 1979, Armarego et al. Aust J Chem 37 355 1984, Beilstein 26 III/IV 4032.]

InChI:InChI=1/C9H15N5O3.2ClH/c1-3(15)6(16)4-2-11-7-5(12-4)8(17)14-9(10)13-7;;/h3-4,6,12,15-16H,2H2,1H3,(H4,10,11,13,14,17);2*1H/t3-,4?,6?;;/m0../s1

Upstream product

• 22150-76-1 biopterin 
• 858127-57-8 (3S,4S)-1-amino-3,4-dihydroxy-2-pentanone 

Downstream Products

• 1041007-05-9 (R)-2-amino-6-((1R,2S)-1,2-dihydroxypropyl)-4-oxo-4,6,7,8-tetrahydro-3H-pteridine-5-carboxylic acid benzyl ester 
• 102340-67-0 p-quinonoid (6R)-dihydrobiopterin hydrochloride 

Relevant articles and documents

Chemical synthesis and purification method of biopterin (by machine translation)

The method, uses diacetyl biopterin as a raw material, to hydrolyze, with diacetyl biopterin to obtain the salpterin crude, obtained by extracting,hydrogenated,acid after the hydrolysis reaction time is short. and obtaining the methotrexate crude product, according to the method . The method is short in production cycle, cost, and suitable for industrial production. after recrystallization of the mixed solution . The method is simple,efficient, % by weight of the methotrexate aqueous solution obtained by. the method. (by machine translation)

METHOD FOR SYNTHESIZING SAPROPTERIN DIHYDROCHLORIDE

Disclosed is a method for synthesizing sapropterin dihydrochloride. The present invention reduces a synthesis route of the sapropterin dihydrochloride, introduces a chiral center in an asymmetric synthesis manner, in which a tetrahydrofuran solution containing a samarium catalyst is adopted as a catalyst, and obtains a target compound having a high antimer isomerism value by means of selective catalysis. The yield is improved, raw materials are cheap and readily available, and the cost is significantly reduced, hence providing an effective scheme for mass industrial production of the sapropterin dihydrochloride.

METHOD FOR SYNTHESIZING SAPROPTERIN DIHYDROCHLORIDE

Disclosed is a method for synthesizing sapropterin dihydrochloride. The present invention reduces a synthesis route of the sapropterin dihydrochloride, and resolves a racemate intermediate or an intermediate having a low antimer isomerism value by using a chiral resolving reagent, thereby obtaining an intermediate having a high antimer isomerism value. Raw materials are cheap and readily available, and the cost is significantly reduced, hence providing an effective scheme for mass industrial production of the sapropterin dihydrochloride.