Pyrimidines and pteridines

Biologically active lluorinated purines, pyrimidines, and pteridines, advances in preparation of 87T3123. 

Condensation of 2-amino-2-deoxy-D-glucose and 1-amino-l-deoxy-D-fructose with nitromethane led to tetrahydroxybutylpyrrole derivatives (35) and (36) respectively. 5 -Phosphates of a variety of D-ribityl-substituted pyrimidines and pteridines have been synthesized. ... 

Pyrimidines from pteridines and related fused systems... 

Most pteridines are degraded to pyrazines and when they do yield pyrimidines, these may well be the ones from which they were made. However, some useful preparations of pyrimidines from pteridines are known. Thus, reduction of pteridin-7(8//)-one (732) and subsequent hydrolysis yields N-(4-aminopyrimidin-5-yl)glycine (733) (52JCS1620) and hydrolysis of 5,8-dimethylpteridine-6,7(5Ff,8Ff)-dione (734) gives dimethyl-... 

Among its inhibitors are methotrexate (MTX), trimethoprim, and other derivatives of pyrimidines, triazines, pteridines, and related heterocyclic compounds. Some of these inhibitors, such as MTX, bind more tightly to Escherichia coli enzyme than does the substrate dihydrofolate. This fact has been attributed to ion-pair formation between protonated MTX and a negative carboxyl, presumably Asp-27, as well as to hydrophobic interactions.33... 

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. 

Purines (purine = 7//-imidazo [4,5-rf]pyrimidine, C5H4N4) and pteridines (pteridine = pyrazino [2,3-d]pyrimidine, C6FI4N4) are compounds consisting of two fused A-heterocyclic rings. Adenine and guanine are important purines. They are used, for example, as building blocks for nucleotides (see discussion below). Folic acid (a vitamin), methopterin, and methotrexate are typical pteridines. 

The substitution of pteridines at positions adjacent to the pyridine-like nitrogen atoms in either the pyrimidine or the pyrazine is a well-established synthetic procedure and remains an important contributor to the synthesis of complex substituted pteridines. Significant extensions of these methods have been described at both the pyrimidine and pyrazine rings. 

The natural cofactor of the AAHs, BH4 (Scheme 2), is a heterocyclic compound chemically classified as a pteridine that includes a fused pyrimidine and pyrazine rings. As many other naturally occurring pteridines BH4 has a pterin structure, which includes an amino substituent in position 2 and an oxo group in position 4 of the pyrimidine ring. The term biopterin is reserved for pterins with a dihydroxypropyl group in position 6. 

Hurst, D. T. (1980) An Introduction to the Chemistry and Biochemistry of Pyrimidines, Purines and Pteridines, Wiley, New York... 

The pKz values of pyrimido[4,5-rf]pyrimidin-4-one and pyrimido[4,5-rf]pyrimidine-4-thione have been determined to be 7.20 and 6.23, respectively. When compared with the pjKa values of the corresponding purine and pteridine analogs, it can be seen that the pyrimido[4,5-d]pyrimidines are more acidic. The greater acidity of these compounds can probably be attributed to their lack of ability to form strong internal hydrogen bonds (58JOC1451). 

The diazines (pyridazine, pyrimidine, and pyrazine) are six-membered aromatic heterocycles that have two nitrogens in the ring. Cytosine, thymine, and uracil are derivatives of pyrimidine that are important bases in nucleic acids (DNA and RNA). Heterocyclic analogs of the aromatic hydrocarbon naphthalene include pteridines, which have four nitrogens in the rings. Naturally occurring pteridine derivatives include xanthopterin (a pigment) and folic acid (a vitamin). Methotrexate is a pteridine used in cancer chemotherapy. 

Hurst, D.T. (1980). An introduction to the chemistry and biochemistry of pyrimidines, purines, and pteridines. Wiley, New York. 

The UV spectra for the 7-aminofurazano[3,4-rf]pyrimidines are very similar to those of the sulfur analogues, 7-amino[l,2,5]thiadiazolo[3,4-d]pyrimidines and also to the correspondingly substituted pteridines. This similarity suggests an isoelectronic relationship... 

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. 

Tautomerism of [6.6]biheterocycles was not covered in the previous review (76AHCS1). Since then, several surveys appeared on pyrazino[2,3-d]pyrimidines or pteridines (135) with some coverage of tautomerism, with the most recent by Pfleiderer [96CHEC(7)679, and references therein]. The results on pteridines not included in the previous surveys, are discussed in this section. Limited data on other heterocycles are also covered. 

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