Xanthine Synthesis

Ai,A/-bis(hydroxymethyl) formamide [6921-98-8] (21), which in solution is in equiUbrium with the monomethylol derivative [13052-19-2] and formaldehyde. With ben2aldehyde in the presence of pyridine, formamide condenses to yield ben2yhdene bisformamide [14328-12-2]. Similar reactions occur with ketones, which, however, requite more drastic reaction conditions. Formamide is a valuable reagent in the synthesis of heterocycHc compounds. Synthetic routes to various types of compounds like imida2oles, oxa2oles, pyrimidines, tria2ines, xanthines, and even complex purine alkaloids, eg, theophylline [58-55-9] theobromine [83-67-0], and caffeine [58-08-2], have been devised (22). 

Deamination, Transamination. Two kiads of deamination that have been observed are hydrolytic, eg, the conversion of L-tyrosiae to 4-hydroxyphenyUactic acid ia 90% yield (86), and oxidative (12,87,88), eg, isoguanine to xanthine and formycia A to formycia B. Transaminases have been developed as biocatalysts for the synthetic production of chiral amines and the resolution of racemic amines (89). The reaction possibiUties are illustrated for the stereospecific synthesis of (T)-a-phenylethylamine [98-84-0] (ee of 99%) (40) from (41) by an (5)-aminotransferase or by the resolution of the racemic amine (42) by an (R)-aminotransferase. 

Allomaltol, methyl — see Pyran-4-one, 5-methoxy-2-methyl-Allopurinol applications, 5, 343 metabolism, 1, 237 synthesis, 5, 316, 340 tautomerism, 5, 308 xanthine oxidase inhibition by, 1, 173 Allopurinol, oxy-applications, 5, 343 synthesis, 5, 316 Alloxan... 

Boroxazothienopyridines, 4, 1029-1032 Borsche synthesis, 3, 44 Botrydiplodin mass spectrometry, 4, 585 Boulton-Katritzky rearrangement, 5, 288 Bovine milk xanthine oxidase substrates, 1, 234 Bradsher reaction... 

Paraxanthine—see Xanthine, 1,7-dimethyl-Parent name nomenclature, 1, 35 Parham cycloalkylation in chroman synthesis, 3, 783 Paromomycins as pharmaceuticals, 1, 154 Partial charge transfer from donor to acceptor stacks, 1, 350 Pasteurellosis... 

Xanthine, 8-ethyl-synthesis, 5, 574 Xanthine, 9-hydroxy-8-methyl-synthesis, S, 596 Xanthine, 1-methyl-deuterium-hydrogen exchange, S, 527 methylation, S, 533 occurrence, S, 598 reduction, 5, 541 synthesis, S, 589 Xanthine, 3-methyl-deuterium-hydrogen exchange, S, 528 methylation, S, 533 reduction, S, 541 synthesis, S, 595 Xanthine, 7-methyl-deuterium-hydrogen exchange alkylation, S, 527 reduction, S, 541 synthesis, S, 587 Xanthine, 8-methyl-synthesis, S, 574 Xanthine, 9-methyl-methylation, S, 533 nitration, 5, 538... 

Xanthine, 9-methyl-8-methylthio-2-thio-synthesis, S, 590 Xanthine, 7-methyl-8-phenyl-synthesis, S, 588 Xanthine, 7-methyl-2-thio-synthesis, S, 590 Xanthine, 9-methyl-2-thio-synthesis, 5, 590 Xanthine, 8-methylthio-2-thio-synthesis, S, 590... 

Xanthine, 8-phenyl-synthesis, S, 588 Xanthine, 1,3,8,9-tetramethyl-synthesis, S, 588 Xanthine, 2-thio-dethiation, S, 558 Xanthine, 6-thio-synthesis, S, 588 Xanthine, 1,3,8-trimethyl-synthesis, 3, 308 S, 575 Xanthine, 1,3,9-trimethyl-structure, S, 509 Xanthine, 2,3,8-trimethyl-synthesis, S, 574... 

Xanthine anions structure, 5, 509 Xanthine-8-carboxylic acid synthesis, 3, 308, 322 Xanthine oxidase... 

Fig. 4.5 The adenine synthesis can be varied to give other purine derivatives. Structures I-IX are those of I aminomalonitrile, II HCN tetramer, III aminoimidazole-carbonitrile, IV 4-aminoimidazole-5-carboxamide, V adenine, VI diaminopurine, VII xanthine, VIII guanine and IX hypo xanthine (Sanchez et al., 1966a)... 

Huang S-T, Liao J-S, Fang H-W, Lin C-M (2008) Synthesis and anti-inflammation evaluation of new C60 fulleropyrrolidines bearing biologically active xanthine. Bioorg. Med. Chem. Lett. 

J. Leppanen, J. Huuskonen, J. Savolainen, T. Nevalainen, H. Taipale, J. Vepsalainen, J. Gynther, T. Jarvinen, Synthesis of a Water-Soluble Prodrug of Entacapone , Bioorg. Med. Chem. Lett. 2000, 10, 1967-1969 R. Sauer, J. Maurinsh, U. Reith, F. Ftille, K. N. Klotz, C. E. Muller, Water-Soluble Phosphate Prodrugs of l-Propargyl-8-styryl-xanthine Derivatives, A2A-Selective Adenosine Receptor Antagonists , J. Med. Chem. 2000, 43, 440-448. 

AHopurinol inhibits xanthine oxidase and also can reduce purine synthesis by inhibiting PRPP amidotransferase (provided HPRT is active). Hyperuricemia and gout often accompany the following conditions ... 

X-ray crystallography, 40 20-21 synthetic models, 40 23-48 xanthane oxidase, 40 21-23 chalcogenide halides, 23 370-377, 413 Chevrel phases, 23 376-377 metal-metal bonding, 23 330, 373 structural data, 23 373-376 as superconductors, 23 376 synthesis, 23 371-372 chloride, 46 4-24, 35-44 heterocations of, 9 290, 291 cluster compounds, 44 45-46 octahedral, 44 47-49, 53-63 electronic structure, 44 55-63 molecular structure, 44 53-54 synthesis, 44 47-49 rhomboidal, 44 75-82 solid-state clusters and, 44 66-72, 74-75, 80-82, 85-87 tetrahedral, 44 72-75 triangular, 44 82-87 cofactor, 40 2, 4-12 anaerobic isolation, 40 5 molybdopterin and, 40 4-8 reduced form, 40 12 synthesis, 40 8-12 xanthine oxidase, 45 60-63 complexes... 

Allopurinol, in contrast to the uricosuric drugs, reduces serum urate levels through a competitive inhibition of uric acid synthesis rather than by impairing renal urate reabsorption. This action is accomplished by inhibiting xanthine oxidase, the enzyme involved in the metabolism of hypoxanthine and xanthine to uric acid. After enzyme inhibition, the urinary and blood concentrations of uric acid are greatly reduced and there is a simultaneous increase in the excretion of the more soluble uric acid precursors, xanthine and hypoxanthine. 

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