Pyrimidines, literature reviews

Tlie chemistry of one of the four possible classes of 1,2,4-triazolopyrim-idiiies, namely l,2,4-triazolo[l,5- ]pyrimidines, was reviewed in 1993 by G. Fischer [93AHC(57)81]. In two previous chapters published in this series we reviewed the chemistry of l,2,4-triazolo[4,3- ]pyrimidines [99AHC(73)131] and their [4,3-c] congeners [99AHC(75)243]. In this chapter we survey the fourth and last class of 1,2,4-triazolopyrimidines. Tlie literature has been inspected to issue number 26, Volume 129(1998) of Chemical Abstracts. 

The chemistry of the pyrido[l,2-a]pyrimidines was reviewed in 1983 (83AHC241 85MI3). This earlier review covered the chemical literature through the first half of 1981 and surveyed 469 publications. In the last 12 years the appearance of another 500 papers and patents indicates the increasing interest in these compounds. 

The pyridopyrimidines discussed in this review are derived by the ortho fusion of the pyridine and pyrimidine rings through ring carbon atoms. There are four such compounds for which the nomenclature and numbering of Chemical Abstracts (1-4) will be used. Alternative names used in the literature are 1,3,8-triazanaphthalene (1), 1,3,5-tri-azanaphthalene (2), 1,3,7-triazanaphthalene or copazoline (3), and 1,3,6-triazanaphthalene (4). There has been no previous review of the... 

This series in heterocyclic chemistry is being introduced to collectively make available critically and comprehensively reviewed literature scattered in various journals as papers and review articles. All sorts of heterocyclic compounds originating from synthesis, natural products, marine products, insects, etc. will be covered. Several heterocyclic compounds play a significant role in maintaining life. Blood constituent hemoglobin and purines as well as pyrimidines, are constituents of nucleic acid (DNA and RNA) are also heterocyclic compounds. Several amino acids, carbohydrates, vitamins, alkaloids, antibiotics, etc. are also heterocyclic compounds that are essential for life. Heterocyclic compounds are widely used in clinical practice as drugs, but all applications of heterocyclic medicines can not be discussed in detail. In addition to such applications, heterocyclic compounds also find several applications in the plastics industry, in photography as sensitizers and developers, and in dye industry as dyes, etc. 

Numerous publications on uracil and thymine and their role in controlling the metabolism, reproduction, and growth of living systems — in particular in the transcription of genetic information and biosynthesis of proteins — have already appeared in the literature. Therefore, these two important pyrimidines will not be discussed again in the present review. Some pertinent literature references are provided [244—264]. 

Despite this interest, the literature of these compounds has not been reviewed in the covered survey period with exception of a review on l,3-dithiolo[4,5-,7 pyrimidines (system 58) as well as its oxo, dioxo, and aminooxo derivatives . 

The preparation of pyrimidines and hydropyrimidines from thioureas is well established.139,217,218 Since the latest review (1962) covering this reaction,218 several reports of the preparation of heterocyclic compounds by previously reported procedures have appeared in the literature. These involve reactions of thioureas with a,/3-unsaturated ketones,219-224 jS-ketoesters,225-228 aliphatic ketones,229-231 j8-dicar-bonyl compounds,232 and ethyl ethoxymethylenecyanoacetate.233 Selenoureas have also been reported to react with /3-ketoesters to give the analogous 2-selenopyrimidines.234,235 Two reports have appeared of the cyclization of l-/3-carboxyethyl-2-thioureas to hexahydro-pyrimidines in low yields in the presence of acetic anhydride 238,237 however, tetrahydrothiazines are the predominant products in these reactions. 

The chemistry of the pyrido[l,2-a]pyrimidines has previously been reviewed by Mosby1, who found 43 references to this ring system while covering the literature up to 1957. Many of the early articles have been found to contain erroneous statements, and therefore these publications have also been included in the present work. 

Hermecz and Meszaros have surveyed the chemistry ot pyridol l,2- pyrimidines (and have included 469 reterences). The only earlier review that covers the literature up to 1957 listed a mete 43 tefeiences. Finally, Timpe and FTtsov have dealt with (he enormous subject of pseudoazu-lenes, defined in a broad way to cover a wide vaiiety ot bicyclic heteiocy-cles. 

Isolated and benzo-fused diazine rings are key structural elements in many natural and synthetic compounds of current, active interest. This contribution relates highlights from many of the studies on the diazines pyridazine, pyrimidine, pyrazine, and their benzo-fused derivatives cinnoline, phthalazine, quinazoline, quinoxaline, and phenazine published in English in the journal literature during 1995, as covered by Chem. Abstr. through volume 124, issue 9. Review articles published in 1994 and not cited in Prog. Heterocycl. Chem. have been included. 

There is some imbalance in studying and describing those two phenomena. In spite of that, both of them were first predicted computationally [11, 12] only nonplanarity of amino- group had been confirmed experimentally [13] and attracted considerable attention in the literature (see, for example [14, 15]). In case of conformational flexibility of DNA bases, only indirect experimental evidences have been revealed [16-18], Therefore, in this review, we discuss in detail the current status of investigations on the ability of pyrimidine ring of DNA bases to fluctuate between planar and nonplanar states. 

N8-hydroxyamino group is acylated with a carbon piece related to mevalonic acid — acetic acid, fnwts- 3-methylglutacomc acid, cis or trans 5-hydroxy-3-methylpent-2-enoic acid (63). In albomycin S2, the hydroxyl group of the first serine is linked to a pyrimidine moiety by means of sulfur (137), the substantial literature in the U.S.S.R. on this antibiotic has been reviewed through 1964 (81). Ferric ion combines with the trihy-droxamate center concomitant with the ionization of three hydrogen ions. 

The interest in, and importance of, the compounds which are the subject of this chapter is indicated by the very large number of references (several thousand) which have been published since 1982. A survey of the literature in which the two heteroatoms in the six-membered ring are nitrogen reveals a considerable variety of interest. The fused diazines were covered to some extent in CHEC-I and the pyrrolopyrimidines had been the subject of a previous review <74S837>. Not surprisingly, the pyrrolo[2,3-d]pyrimidines and pyrrolo[3,2-d]pyrimidines, also known as 7- and 9-deazapurines, respectively, have commanded the most interest in laboratories around the world. Pyrrolopyridazines, although a much less studied subject, have also been reviewed [Pg.230]

In many cases, the literature since CHEC-I of those systems in class (i) has been extensive, mainly because most are related to the purine nucleus by the inclusion of a further heteroatom for example azapurine derivatives which have shown pharmaceutical or physiological action. The methods of synthesis, except in a few cases, have not changed since the publication of CHEC-I and thus more emphasis has been placed on the physical properties, reactivity, and reactivity of substituents of compounds within these systems. In contrast, in most cases very little literature is available for systems of class (ii) and synthesis has assumed paramount importance. Only two reviews since the early 1980s are applicable to this chapter the conversion of [l,2,5]oxadiazolo[3,4- f]pyrimidines (9) to pteridines <82MI 713-01) and the chemistry and physical properties of 1,2,3-triazolo[4,5-djpyrimidines (7) <86AHC(39)l 17>. The incidence of publications relating to the use of Structures (1)-(50) in such applications as pharmaceuticals, agrochemicals, and even explosives has increased since the publication of CHEC-I and these are discussed in Section 7.13.10. 

The primary synthesis of pyrazines from other heterocyclic systems has a body of literature that is quite modest by comparison with those for pyridazines1687 and pyrimidines.1688 Earlier information on such syntheses has been summarized in Barlin s original book1686 and some more recent data have been reviewed thoughtfully from time to time.1677,1689... 

The most widely used route to purines has undoubtedly involved the addition of an imidazole ring to an appropriate pyrimidine. This particular route has probably dominated the early literature because of the relative ease of synthesis of the requisite pyrimidines compared with the lack, until recently, of useful routes to imidazole precursors. The synthesis of pyrimidines has been exhaustively reviewed <62HC(16)l) and full details have been provided of the synthesis of the specfic pyrimidines used in purine synthesis. The pyrimidine moiety... 

The literature documents various situations in which C deamination is enhanced. These situations include the presence of C in cyclobutane pyrimidine dimers (a form of DNA damage caused by exposure to UV radiation see later discussion) or in mis-pairings with other bases or with alkylated bases (1). Cytosine deamination is also promoted in the presence of nitrons acid, a reaction that although not considered in this review, has lent much to our understanding of possible chemical mechanisms of spontaneous deamination (1). 

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