Pteroic acid

Radiolabeled folate provides a powerful tool for folate bioavaHabiUty studies in animals and for diagnostic procedures in humans. Deuteration at the 3- and 5-positions of the central benzene ring of foHc acid (31) was accompHshed by catalytic debromination (47,48) or acid-cataly2ed exchange reaction (49). Alternatively, deuterium-labeled fohc acid (32) was prepared by condensing pteroic acid with commercially available labeled glutamic acid (50). 

A number of deaza analogs of pteroic acid (182, Ri = R2 = OH) have been prepared and examined by Rydon el al. as antagonists of folic acid in Streptococcus faecalis and Lactobacillus casei. Two of the pyrido[3,2-d]pyrimidines (183, R = OH or OEt, R2 = NH2) showed... 

Several quinoxaline analogs of pteroic acid (114) and pteroyl-glutamic acid (115) have been prepared. " - Quinoxaline-2-aldehyde,... 

There is one literature report of a pyrimido[5,4-J]pyrimidyl analogue (186) of pteroic acid, which can be viewed as an 8-deaza-7-aza derivative [110]. In this approach (Scheme 3.35), hydroxyacetamidine was condensed with mucobromic acid in a modified Budesinsky procedure to produce 2-hydroxy-... 

As part of an extensive investigation of syntheses of deaza derivatives of pteroic acid, Rydon s group described the first synthesis of 4-amino-4-deoxy-5,8-dideazapteroic acid (212a) [99, 119]. In their approach (Scheme 3.39), 4-methylanthranilic acid was fused with urea to give (207) from which (208) was obtained in two steps. Attempts to brominate (208) directly were unsatisfactory, necessitating protection of the amino groups by benzoylation giving... 

A group from the Midwest Research Institute has described two approaches to purine analogues of AP (281a) and MTX (281b) [151]. A shown in Scheme 3.50, the first, patterned after previous reports of the pteroic acid ... 

A complementary approach to (511) and (512) (Scheme 3.101 and 3.102) [53, 216] was patterned after methodology developed in Taylor s laboratories [217,218]. Alkylation of ethyl/>-mercaptobenzoate with the chloromethylpyra-zine (16a) furnished (513). Guanidine cyclization to give (514) followed by saponification resulted in concomitant hydrolysis of the 4-amino group to provide the pteroic acid analogue (509), which was converted to (511) in the usual manner. In order to avoid hydrolysis of the 4-amino group, the initial... 

Tetrahydrofolate accepts methyl groups, usually from serine. The product, N5,N10-methylene-tetrahydrofolate, is the central compound in 1-carbon metabolism. Tetrahydrofolate can also accept a methyl group from the complete breakdown of glycine. In Figure 5-2, only the N5, C6, and N10 atoms of the pteroic acid are shown for clarity. 

Fig. 6 Radiopharmaceuticals of folic acid. The pteroic acid is black, pteroic acid + glutamic acid (blue) gives folic acid...

The pteroic acid moiety of tetrahydrofolate consists of a reduced pteridine ring and p-aminobenzoic acid. Folate from the diet is absorbed by the intestinal mucosa and in two enzymatic steps is reduced to tetrahydrofolate which is the active form of the coenzyme. Mammals cannot synthesize folate this normally does not present a problem because microorganisms of the intestinal tract readily do so. 

As shown in Figure 10.1, folic acid consists of a pteridine linked at C-9 to p-aminobenzoic acid, forming pteroic acid. The carboxyl group of the p-aminobenzoic acid moiety is linked by a peptide bond to the amino group of glutamate, forming pteroyl monoglutamate. 

Folic acid is a conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid (PABA) that forms pteroic acid. 

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