62989-33-7

Usage

Uses

Treatment of mild-to-moderate phenylketonuria (PKU).

InChI:InChI=1/C9H15N5O3/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)/t3-,4?,6-/m0/s1

Synthetic route

biopterin (22150-76-1) → (1'R,2'S,6R)-2-amino-6-(1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one-dihydrochloride (62989-33-7) + (6S)-tetrahydrobiopterin (62961-57-3)

Conditions	Yield
With hydrogen; platinum(IV) oxide In water at 15℃; for 18h; pH=11.8;	A 79% B n/a
With potassium hydroxide; dipotassium hydrogenphosphate; hydrogen; platinum(IV) oxide In water at 20℃; under 735.5 Torr; for 4.5h; pH 11.4;	A 67% B n/a
With potassium hydroxide; dipotassium hydrogenphosphate; hydrogen; platinum(IV) oxide In water at 20℃; under 735.5 Torr; Product distribution; the influence of pH;

p-quinonoid (6R)-dihydrobiopterin (79647-29-3) → 7,8-dihydro-L-biopterin (6779-87-9) + (1'R,2'S,6R)-2-amino-6-(1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one-dihydrochloride (62989-33-7) + biopterin (22150-76-1)

Conditions	Yield
pH=7;
In water Product distribution; pH 3.5 ; half life time; other pH; also with NADPH;

(6R)-2-acetamido-5,8-diacetyl-6-[(1R,2S)-1,2-bis(acetyloxy)propyl]-5,6,7,8-tetrahydropteridin-4(3H)-one → (1'R,2'S,6R)-2-amino-6-(1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one-dihydrochloride (62989-33-7)

Conditions	Yield
With hydrogenchloride In water at 22℃;

6-((1R,2R)-1,2-dihydroxy-3-phenylthiopropyl)-2-[(methylethyl)amino]-3-hydropteridin-4-one → (1'R,2'S,6R)-2-amino-6-(1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one-dihydrochloride (62989-33-7)

Conditions	Yield
With BH4; hydrogen; nickel In ethanol at 60℃; under 3750.38 Torr; for 17h;

dioxomolybdenum(VI) dichloride (13637-68-8) + (1'R,2'S,6R)-2-amino-6-(1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one-dihydrochloride (62989-33-7) → trichloro{(1'R,2'S,6R)-2-iminio-6-(1',2'-dihydroxypropyl)-3,6,7,8-tetrahydropteridin-4(3H)-one-O(4),N(5)}oxomolybdenum(IV)*MeOH

Conditions	Yield
In methanol byproducts: H2O, HCl; under protective gas, toluene/cyclohexane added, allowed to stand at 4°C overnight; filtrated, dried in high vacuum, elem. anal.;	97.1%

(1'R,2'S,6R)-2-amino-6-(1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one-dihydrochloride (62989-33-7) → 7,8-dihydrobiopterin (1262750-77-5)

Conditions	Yield
With oxygen In aq. phosphate buffer at 25℃; for 1h; pH=7.2; Kinetics;	34.6%

(1'R,2'S,6R)-2-amino-6-(1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one-dihydrochloride (62989-33-7) → 7,8-dihydrobiopterin (1262750-77-5) + D-erythro-biopterin (13039-62-8)

Conditions	Yield
With oxygen In aq. acetate buffer at 25℃; for 1h; pH=7.2;	A 15.7% B 24.2%

di-tert-butyl dicarbonate (24424-99-5) + (1'R,2'S,6R)-2-amino-6-(1',2'-dihydroxypropyl)-5,6,7,8-tetrahydropterin-4(3H)-one-dihydrochloride (62989-33-7) → [6R(1R,2S)]-2-t-butoxycarbonylamino-4-t-butoxycarbonyloxy-5,8-di-t-butoxycarbonyl-6-(1,2 dihydroxypropyl)-5,6,7,8-tetrahydropterdin (908119-99-3)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20 - 60℃; for 20h;

Upstream product

• 22150-76-1 biopterin 
• 79647-29-3 p-quinonoid (6R)-dihydrobiopterin 

Downstream Products

• 1262750-77-5 7,8-dihydrobiopterin 
• 13039-62-8 D-erythro-biopterin 

Relevant academic research and scientific papers

PROCESSES FOR PREPARING TETRAHYDROBIOPTERIN, AND ANALOGS OF TETRAHYDROBIOPTERIN

Process for the preparation of tetrahydrobiopterin from neopterin and/or 6-substituted pterins with an improved yield and a high stereoselectivity. Also disclosed herein are novel individual intermediates prepared in the preparation of tetrahydrobiopterin, such as selectively protected neopterin useful for the preparation of tetrahydrobiopterin.

Quinonoid Dihydrobiopterin, an Important Metabolic Intermediate of Biopterin Cofactor in the Aromatic Hydroxylation of Amino Acids

p-Quinonoid (6R)-dihydrobiopterin hydrochloride was synthesized from (6R)-5,6,7,8-tetrahydrobiopterin dihydrochloride by hydrogenperoxide in the presence of potassium iodide.Several characters of quinonoid dihydrobiopterin were examined.

HYDROGENATION OF BIOPTERIN AND ITS ANALOGUES; APPLICATION FOR THE CONVENIENT PROCEDURE OF BIOPTERIN COFACTOR AND RELATED 5,6,7,8-TETRAHYDROPTERINS

A large scale and stereoselective hydrogenation of biopterin to (6R)-5,6,7,8-tetrahydrobiopterin was developed.The procedure was applied for various hydroxyalkylpterins such as neopterin and diastereomers of biopterin.

HIGHLY STEREOSELECTIVE PROCEDURE FOR (6R)-TETRAHYDROBIOPTERIN COFACTOR

(6R)-Tetrahydrobiopterin cofactor for aromatic amino acid hydroxylases was synthesized stereoselectively by catalytic hydrogenation of biopterin over platinum oxide at pH 11.4 and subsequent crystallization from hydrochloric acid and ethanol.