Biopterin 7-hydroxy

A strategy has been described for the synthesis of 2-ethyIthio-6-(3-hydroxy-1,2-0-isopropylidenepropyl)pteridin-4(3//)-one 90 which can be used as a useful intermediate for the conversion of neopterin to biopterin. Diaminopyrimidinone 86 reacts with D-arabinose phenylhydrazone 87, the obtained diastereomeric mixture 88 is converted into its isopropylidene derivative 89 which under oxidation conditions yields 90 <00H(53)1551>. 

There is a long-standing myth that ascorbate is required for the hydroxy-lation of tyrosine to dihydroxyphenylalanine (see Figure 13.4) and the similar reactions of phenylalanine and tryptophan hydroxylases. This belief arose as a result of early studies of a nonenzymic reaction to synthesize the hydroxy-lated amino acids for further study. It became established that ascorbate was required for these hydroxylations, and it is stUl common to include it in the incubation buffer. So far from requiring ascorbate, the addition of relatively low concentrations of ascorbate to preparations of tyrosine hydroxylase that has been activated by cAMP-dependent protein kinase results in irreversible loss of activity, although the unactivated form of the enzyme is unaffected by ascorbate (WUgus and Roskoski, 1988). As discussed in Section 10.4.1, these enzymes are biopterin-dependent, and require dUiydrobiopterin reductase and NADPH for activity. There is, however, evidence that, in some nerve cell lines in culture, tyrosine hydroxylase may be induced by ascorbate (Seitz et al., 1998). 

R-Tetrahydro-erythro-biopterin dihydrochloride (BH4.2HCI, 67 -2-amino-4-hydroxy-6-[ lR,25 -l,2-dihydroxypropyl]-5,6,7,8-tetrahydropteridine 2HC1) [69056-38-8] M 316.2, m... 

A small subset of patients with hyperphenylalaninemia show an appropriate reduction in plasma phenylalanine levels with dietary restriction of this amino acid however, these patients still develop progressive neurologic symptoms and seizures and usually die within the first 2 years of life ("malignant" hyperphenylalaninemia). These infants exhibit normal phenylalanine hydroxylase (PAH) activity but have a deficiency in dihy-dropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydro-biopterin (BH4), a cofactor of PAH (see Fig. 39.18). Less frequently, DHPR activity is normal but a defect in the biosynthesis of BH4 exists. In either case, dietary therapy corrects the hyperphenylalaninemia. However, BH4 is also a cofactor for two other hydroxy-lations required in the synthesis of neurotransmitters in the brain the hydroxylation of tryptophan to 5-hydroxytryptophan and of tyrosine to L-dopa (see Chapter 48). It has been suggested that the resulting deficit in central nervous system neurotransmitter activity is, at least in part, responsible for the neurologic manifestations and eventual death of these patients. 

Folic acid (I), biopterin (II), neopterin (III) and xanthopterin (IV) belong to the pteri-dine family. All of them are 2-amino-4-hydroxi-pteridines with different substituents at C-6. 

The ability of light to catalyze the formation of 2-amino-4-hydroxy-pteridine-6-carboxylic acid and 2-amino-4-hydroxypteridine from these various derivatives related to biopterin has suggested the possibility that these... 

Deoxy-[5- H]-L-arabinose has been synthesized from L-arabinose by reduction (NaBD4-DMSO) of the 5-tosylate of its diethyl dithioacetal, and converted into [3 - H] biopterin. Methyl oligobiosaminide (17), its 6-hydroxy-derivative (18), and their 2- and 3-deoxy-analogues (19) and (20) have been synthesized by coupling 4-amino-4-deQj -hexose residues with the pseudo-sugar epoxide (16) (Scheme 3). While almost no glycosidase... 

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