Folic acid Tetrahydro

Folic acid — Tetrahydro-folic acid Transfer one-carbon units 1 Synthesis of methionine, purines, and thymine 1... 

Catalytic reduction of folic acid to 5,6,7,8-tetrahydrofolic acid (225) proceeds fast in trifluoroacetic acid (66HCA875), but a modified method using chemical reductants leads with sodium dithionite to 7,8-dihydrofolic acid (224). Further treatment with sodium borohydride gives (225) which has been converted into 5-formyl-(6i ,S)-5,6,7,8-tetrahydro-L-folic acid (leucovorin) (226) by reaction with methyl formate (equation 70) (80HCA2554). 

Folic acid, 4-amino-4-deoxy-10-methyl-, 1, 164 3, 325 as anticancer drug, 1, 263 biological activity, 3, 325 Folic acid, 4-amino-10-methyl-toxicity, 1, 141 Folic acid, 7,8-dihydro-biosynthesis, 3, 320 synthesis, 1, 161, 3, 307 Folic acid, 4-dimethylamino-hydrolysis, 3, 294 Folic acid, 5-formiminotetrahydro-biological activity, 3, 325 Folic acid, 5-formyl-5,6,7,8-tetrahydro-biological activity, 3, 325 chirality, 3, 281 occurrence, 3, 325 Folic acid, 10-forfnyltetrahydro-biological activity, 3, 325 Folic acid, 5,10-methenyl-5,6,7,8-tetrahydro-biological activity, 3, 325 chirality, 3, 281 Folic acid, 5-methyl-chirality, 3, 281 Folic acid, 9-methyl-toxicity, 1, 141... 

Folic acid, 5,10-methylene-5,6,7,8-tetrahydro-biological activity, 3, 325 chirality, 3, 281... 

Folic acid, 5-methyltetrahydro-biological activity, 3, 325 oxidation, 3, 308 Folic acid, iV-nitroso-carcinogenicity, 1, 141 Folic acid, 10-oxa-synthesis, 3, 327 Folic acid, 4-piperidyl-hydrolysis, 3, 294 Folic acid, 5,6,7,8-tetrahydro-chirality, 3, 281 synthesis, 1, 161 Folic acid, 10-thio-synthesis, 3, 327... 

Leucovorin — see L-Folic acid, 5-formyl-(6R,S)-5,6,7,8-tetrahydro-, 3, 307 Levallorphan... 

Methyl-tetrahydro folic acid is furthermore, together with vitamin B12 and B6, required to regenerate homocysteine (see Vitamin B12, Fig. 1). Homocysteine results when methionine is used as a substrate for methyl group transfer. During the last few years, homocysteine has been acknowledged as an independent risk factor in atherosclerosis etiology. Folic acid supplementation can help reduce elevated homocysteine plasma levels and is therefore supposed to reduce the risk of atherosclerosis as well [2]. 

Tetrahydro folic acid 5-meiliyl-tetiahydro folic acid... 

The biologically active relatives of folic acid and biopterin are the tetrahydro compounds with a reduced pyrazine ring. Reduction to this level occurs rapidly in vivo. The corresponding electrochemical process is well illustrated by reduction of the N-methylated analogue 28 [95], Reduction to the 5,8-dihydro stage is a reversible two-electron and two-proton process. The product rapidly tautomerises to the... 

Thymidylate synthase requires methylene tetrahydro-folate as a reductant and the reduction of dihydrofolate is also an important part of the process. In protozoa dihydrofolate reductase and thymidylate synthase occur as a singlechain bifunctional enzyme.f As has been pointed out in the main text, such folic acid analogs as methotrexate are among the most useful anticancer drugs. By inhibiting dihydrofolate reductase they deprive thymidylate synthase of an essential substrate. 

More sophisticated mass spectrometric methods have been found in the electrospray (ES-MS) and plasma desorption (PD-MS) techniques which have successfully been applied directly to nonvolatile pteridines. A small peak can be detected with folic acid at m/z = 441 together with the mono-, di-, and trisodium species. The dihydro- and tetrahydro derivatives also give the expected results <83Mi 718-05). Fast atom bombardment (FAB) works also with folic acid in special matrices and is another tool for structural studies <83MI 718-08). Even in a molar mixture of 5-methyl-5,6,7,8-tetrahydropterin and tris(pentane-2,4-dionato)iron(III), the metal-pterin complex could be detected by ES-MS <92HCA1955>. 

Various antileukemic agents related to methotrexate, such as 5-deazaaminopterin (385), 5-deaza-folic acid (389) <83JOC4852>, 10-deazaaminopterin (386), 10-deazafolic acid (390) <88JOC35>, 5,10-dideazafolic acid (391), 5,10-dideazaaminopterin (387), and its 5,6,7,8-tetrahydro derivative (392) <85JMC914> are also synthetically available by this method. This route is even successful in the preparation of poly glutamate derivatives of antifolates <9iJOC3386>. 

The synergistic antimicrobial activity of co-trimoxazole results from its inhibition of two sequential steps in the synthesis of tetrahydro-folic acid sulfamethoxazole inhibits the incorporation of PABA into folic acid, and trimethoprim prevents reduction of dihydrofolate to tetrahydrofolate (see Figure 29.5). Co-trimoxazole exhibits more potent antimicrobial activity than sulfamethoxazole or trimethoprim alone (seed Figure 29.6). 

Faessel HM, Slocum HK, Rustum YM, Greco WR. 1999. Folic acid-enhanced synergy for the combination of trimetrexate plus the glycinamide ribonucleotide formyltransferase inhibitor 4-[2-(2-amino-4-oxo-4,6,7,8-tetrahydro-3H-pyrimidino[5,4,6][l,4]thiazin-6-yl)-(S)-ethyl]-2,5-thienoyl amino-L-glutamic acid (AG2034)—comparison across sensitive and resistant human tumor cell lines. Biochem Pharmacol 57 567-577. 

Benkovic. S. J., Benkovic, P. A., and Chrza-nowski, R., Studies on inodcls of tetrahydro-folic acid. II. Additional observations on the mechanism for condensation of formaldehyde with tetrahydrcxjuinoxaline analogs, J. Am. Chem. Soc., 92, 523, 1970. 

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