Pteridines from purines

Pteridine is pyrazino[2,3-r/]pyrimidine, and the two principal synthetic routes are therefore the construction of the pyrazine on suitable pyrimidine precursors, or the annulation of a pyrimidine ring to a suitably substituted pyrazine. Minor synthetic routes involve the transformation of other ring systems into the pteridine system which can be achieved from purines and oxadiazolopyrimidines. or from tricyclic ring systems by degradation of a third ring. By far the most important route to pteridines involves starting from a suitable pyrimidine pyrimidine-4,5-diamines are the most widely used starting materials. 

Both of these compounds are derived biologically from purines, and the dimethyl derivative but not the monomethyl derivative serves as a biological precursor of riboflavin. The latter may possibly be related to the biosynthesis of other pteridines. Until the discovery of these two pteridine derivatives, all other naturally occurring pteridine derivatives had been found to be derivatives of 2-amino-4-hydroxypteridine. 

Xanthopterin and isoxanthopterin in which the carbon atom at position 4 of the pteridine was labeled with were prepared by Korte and Barke-meyer 18) and in a brief communication they stated that S. faecalis R and certain yeasts had some capacity to convert these pteridines to folic acid or to degrade them to uracil 19). If the degradative pathway of pteridines to uracil were reversible this would represent a possible route of pteridine biosynthesis from a pyrimidine arising either via orotic acid or possibly from purines. 

The only antimalarial drugs whose mechanisms of action are reasonably well understood are the drugs that inhibit the parasite s ability to synthesize folic acid. Parasites cannot use preformed folic acid and therefore must synthesize this compound from the following precursors obtained from their host p-aminobenzoic acid (PABA), pteridine, and glutamic acid. The dihydrofolic acid formed from these precursors must then be hydrogenated to form tetrahydrofoUc acid. The latter compound is the coenzyme that acts as an acceptor of a variety of one-carbon units. The transfer of one-carbon units is important in the synthesis of the pyrimidines and purines, which are essential in nucleic acid synthesis. 

Pyrimido[l,2-a][l,8]naphthyridines synthesis, 2, 599 Pyrimido[5,4-c]oxadiazine purine synthesis from, 5, 591 Pyrimido[4,5-6][ l,4]oxazine synthesis, 3, 312 Pyrimido[2,1 -6]pteridine structure, 3, 284 Pyrimido[5,4-g]pteridine structure, 3, 284 Pyrimidopurines, 5, 566 Pyrimido[4,5-c]pyridazine, aryl- H NMR, 3, 335... 

The fifth chapter, Tetrahydrobiopterin and Related Biologically Important Pterins by Shizuaki Murata, Hiroshi Ichinose and Fumi Urano, describes a modern aspect of pteridine chemistry and biochemistry. Pteridine derivatives play a very important role in the biosynthesis of amino acids, nucleic acids, neurotransmitters and nitrogenmonooxides, and metabolism of purine and aromatic amino acids. Some pteridines are used in chemotherapy and for the diagnosis of various diseases. From these points of view, this article will attract considerable attention from medicinal and pharmaceutical chemists, and also heterocyclic chemists and biochemists. 

Opening of the azole ring with recyclization over a vicinal substituent gives access to other ring systems, e.g. purines and pteridines. The easy reductive cleavage of the N—O bond is used in the preparation of the latter systems from 7-aminofurazano[3,4-rf]pyrimidines. 

In addition to hydroxylating xanthine and a wide range of purines, pteridines and similar compounds, xanthine oxidase is able to oxidize aromatic and aliphatic aldehydes to the corresponding carboxylic acids. Clearly then, there is a close functional as well as structural relationship between xanthine oxidase and the eukaryotic aldehyde oxidases and prokaryotic oxidoreductases. With xanthine oxidase, the pH dependence of the kinetic parameter (obtained from the substrate concentration dependence... 

A new procedure for the methylation of a number of purine derivatives has been described. The photolysis and pyrolysis of 8-azidocaflfeine (37) has been studied. Noteworthy among the many products isolated from these reactions is the thermally produced pteridine derivative (38) and the photochemically generated (in EtOH) ether (39). 

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