Über Pterinchemie. 60. vorläufige Mitteilung [1]. Eine neue, regiospezifische Synthese von L‐Biopterin

Abstract

A new, regiospecific synthesis of L-biopterine Summary Pure L-biopterine (I) is obtained in 35-40% yield by condensation of 5-desoxy-~arabinose-hydrazone acetate with 2,4,5-triamino-6-hydroxy-pyrimidine, followed by oxidation of the formed tetrahydro-derivative and deacetylation of the L-bioterine diacetate. Catalytic reduction of the L-biopterine gives the expected mixture of two diastereomeric tetrahydro-L-biopterines.

Tetrahydrobiopterin therapy of atypical phenylketonuria due to defective dihydrobiopterin biosynthesis.

“…For four days on a normal diet (about 120 mg phenylalanine/kg per day) the serum phenylalanine increased from 2.1 to 20.4 mg/100 ml (0.127 to 1 .234nmmol/1). Chemicallypure (6 R, S)-BH4 2 HCI, synthesised by Schircks et al (1977) was administered intravenously (25 mg BH4-2 HCI, corresponding to 2.5 mg/kg, in 2 ml isotonic buffer of pH 3 0, containing 25 mg ascorbic acid, 20 mg lactic acid, pH adjusted with 1 N NaOH). Three hours later, the serum phenylalanine decreased to 2.1 mg/100 ml.…”

Kinetics of acid-induced degradation of tetra- and dihydrobiopterin in relation to their relevance as biomarkers of endothelial function

“…Katoh and Akino observed that BH 2 in 0.5 N sulfuric acid (stored overnight at -20°C) was oxidized to biopterin and to a lesser extent dehydroxylated to form deoxysepiapterin (Katoh & Akino, 1966). Likewise, BH 2 in 25% acetic acid was found to be degraded to a number of compounds, the major compound being biopterin even when the reaction was carried out under nitrogen for 20 min at 60°C (Schircks et al, 1978). Formation of biopterin was believed to be due to intermolecular redox reactions.…”

“…However, when it comes to BH 2 , its stability at the low pH used to precipitate proteins is less wellstudied. Some authors observed degradation of BH 2 in acid (Katoh & Akino, 1966;Schircks et al, 1978) and at neutral pH (Fukushima & Nixon, 1979), whereas others have found a high stability of BH 2 in aqueous solution at neutral and acidic pH (Dántola et al, 2008;Maharaj et al, 1990;Heales et al, 1988).…”

Synthesis of ( – )-Biopterin Using (S)-Ethyl Lactate as a Starting Material

“…The mixture was filtered, the residue was washed with acetone, and the filtrate was concentrated in vacuo. The crude product was chromatographed over Si02 to give 13 (14). To an ice-cooled solution of 13 (1.30 g, 7.39 mmol) in CHCl3 (26 ml) was added a solution of SOCl2 (1.00ml, 13.7mmol) in CHCl3 (3mI) over a 10min period, before the temperature was raised to 70°C.…”

“…Thus, the obtained 13 was the optically active form of the intermediate, which has been reported for racemic biopterin by Viscontini et al Accordingly, the transformation of 13 into (-)-biopterin by a six-step sequence was effected by their procedure. Acid 13 was treated with thionyl chloride and then by diazomethane to afford a diazoketone (14) as the major product contaminated with a small amount of acid anhydride. Because it was difficult to separate the mixture by column chromatography, it was immediately converted to a mixture of the corresponding acetoxy ketone (15) and acid anhydrid~.…”