Pterins. VIII. The absolute configuration at C 6 of natural 2-Amino-6-[(1'R,2'S)- 1',2'-dihydroxypropyl]-5,6,7,8-tetrahydropteridin-4(3H)-one (L-erythro-5,6,7,8-tetrahydrobiopterin)

Abstract

The conformation of the side chain of 5,6,7&tetrahydrobiopterint (6) in 0.5 M DC1/D20 is predominantly quasi-equatorial (deduced from 3J (13C4a, 'H 6) 1.1 HZ), and is the same as that of the methyl group in 2-methyl-1,2,3,4-tetrahydroquinoxaline and in 2-amino-6-methyl-5,6,7,8-tetrahydropteridin-4(3H)-one in the same solvent. Because (-)-(2s)-2-methyl-l,2,3,4-tetrahydroquinoxaline (4) and (-)-(6S)-2-amino-6-methyl-5,6,7,8-tetrahydropteridin-4(3H)-one (5) have the same conformation and negative c.d. spectra (O 248 nm and 263 nm respectively) as does the natural 5,6,7,84etrahydrobiopterin (O minimum at 265 nm) in 0.1 M hydrochloric acid, then the absolute conformations of the tetrahydropyrazine rings and the absolute configurations at the chiral centres C2, C 6, and C 6 of compounds (4), (5) and (6) respectively are the same. Hence the absolute configuration at C 6 in natural 5,6,7,84etrahydrobiopterin is R.A convenient synthesis of biopterint on a gram scale is described.

Peroxidase catalysed aerobic degradation of 5,6,7,8‐tetrahydrobiopterin at physiological pH

“…The changes in ultraviolet absorption at 300 nm of BHs (3: 1 mixture of diastereoisomers at C-6. prepared by catalytic reduction of biopterin with platinum oxide in trifluoroacetic acid [19], see below), in oxygen-saturated Tris/HCI buffer pH 7.6 containing peroxidase, with time are similar to those of tetrahydroneopterin [4] and are shown in Fig. 2 is altered in the absence of peroxidase and the time for the absorbance changes from points A to B is an hour instead of a few minutes.…”

Pterin-Dependent Amino Acid Hydroxylases

“…632 While the stereochemistry at C 6 is significant, both of the isomers of BH 4 or its analogues are active. The configuration of the BH 4 6-dihydroxypropyl side chain, formed by DHPR reduction, was determined to be R. [633][634][635] With PAH, the natural (6R)-BH 4 isomer has a V max ∼4 times that of the unnatural 6(S)-BH 4 , with no change in K m value or any uncoupling of cofactor oxidation from tyrosine formation (vide infra). 130 The dihydroxypropyl side chain allows relatively straightforward separation of the isomers of BH 4 .…”

HPLC-Based Analysis of Impurities in Sapropterin Branded and Generic Tablets

“…Since the majority of them were commercially available, injection of the standards in the same HPLC conditions, allowed for the confident identification of the compounds as reported in Table 1. In particular, compound 6 was assigned as (6R)-tetrahydrobiolumazine, since it co-eluted with the commercially available product of sapropterin hydrolysis, while the isomeric compound 7, was assigned as (6S)-tetrahydrobiolumazine by comparison with the synthetic biolumazine mixture, which was obtained by following procedures from the literature [9,10]. Similarly, compound 3 was assigned as 7,8-dihydrobiopterin by comparison with the commercially available standard, while the isomeric compound 4 was tentatively assigned as 5,6-dihydrobiopterin.…”