Purines hydroxy

According to the systematic nomenclature these substances were first named l-f-triazolo[d] pyrimidines in compliance with the general principles of the Ring Index/ More recent papers and Chemical Abstracts indexes use the term i -triazolo[4,5-d]pyrimidine (147) in accord with the lUPAC nomenclature. The numbering of substituents when using the last-mentioned name is different from that of the 8-aza analogs. For the formulas of oxygen and sulfur derivatives names derived from the lactim or thiolactim form are almost exclusively in use (in common with the purine derivatives). These derivatives are thus described as hydroxy and mercapto derivatives, respectively. The name 1,2,3,4,6-pentaazaindene is used only rarely for this system. 

For reasons discussed in Section VI, a survey of the purine series (29) is being made in this Department, but so far no example (including 2-hydroxy- and 8-trifluoromethyl-2-hydroxy-purine) of covalent hydration has come to light. An examination of ionization constants disclosed no apparent anomalies, although the interpretation is made more difficult by the ease of anion formation in the 9-position, which often competes with that from other anionic substituents. The only abnormal spectrum seems to be that of the anion of 2-mercaptopurine which is being further examined. 

The examples in the fourth column (Table IX) concern the protonation of purine and adenine and their derivatives while those of the last column mainly reflect Kleinpeter s contributions (Table VIII) to the functional tau-tomerism of 7-hydroxy-l,2,4-triazolo[l,5-a]pyrimidines. 

H-Purin und 6-Amino-purin (unter Ammoniak-Abspaltung) liefern in waBrigen Puf-ferlosungen an Quecksilber l,2,3,6-Tetrahydro-9H-purin, das zu 5-Amino-4-(hydroxy-methylamino-methyl)-imidazol hydrolysiert werden kann2. 

CN 3,7-dihydro-7-[2-[(2-hydroxy-i-methyl-2-phenylethyl)amino]ethyl]-l,3-dimethyl-l//-purine-2,6-dione [R-(R, S )]-cafedrine... 

CN 2-hydroxy-A, A,A(-trimethylethanaminium, salt with 3,7-dihydro-1,3-dimethyl-1 H-purine-2,6-dione (1 1)... 

CN 2-amino-l,9-dihydro-9-[[2-hydroxy-l-(hydroxymethyl)ethoxy]methyl]-6//-purin-6-one monosodium salt... 

CN 3,7-dihydro-l,3-dimethyl-7-[2-(sulfooxy)ethyl]-l/7-purine 2,6-dionecompd. with 5-hydroxy-6-methyl-3,4-pyridinedimcthanol (1 1)... 

All these steps proceed to afford free or N -substituted crystalline cytidines 6 in high yields [11] (cf. the preparation of N (tetramethylene)cytidine 6b in 95.4% yield in Section 1.1.). This simple one-pot reaction is also very easy to perform on a technical scale, as are the subsequently discussed analogous silylation-aminations of purine nucleosides and other hydroxy-N-heterocycles (cf. Sections 4.2.4 and 4.2.5). The concept of silylation-activation while simultaneously protecting hydroxyl groups in alcohols, phenols, or phosphoric acids by silylation was subsequently rediscovered and appropriately termed transient protection [16-18]. 

Unfortunately, the two fuU papers on the silylation-amination of pyrimidine [49] and purine nucleosides [64] as discussed in Sections 4.2.3 and 4.2.4, were pubhshed in German and are thus not readily accessible, although a few detailed procedures from Sections 4.2.3 and 4.2.4 were subsequently published in English [65]. The third paper on the silylation-amination of aromatic hydroxy-N-hetero-cycles, however, as discussed in Section 4.2.5 was, fortunately, pubhshed in English [27]. 

Because aromatic purines and purine nucleosides and free purines such as hypo-xanthine and guanine 242 are readily silylated-aminated [64] (cf Scheme 4.24), it is obvious that 6-membered hydroxy-N-heterocycles are analogously silylated-aminated, with reactivity in the order given in Scheme 4.25 [73] X=OTf is the best leaving group and X=NHSiMe3 (cf the transamination as discussed in Section 4.2.4) is the weakest. 

Hydrates of acids such as Ts0H-H20 can probably also be dehydrated by treatment with silyl esters such as TsOSiMe3 (Scheme 13.1). Likewise, Ts0H-H20 is dehydrated in situ during aminations of hydroxy-N-heterocycles such as purines 242 (Scheme 4.24) or (lH,3H)-quinazoline-2,4-dione 250 (Scheme 4.27) by HMDS 2, in the presence of higher-boiling primary or secondary amines, to give the ami-... 

Small quantities of additional purines and pyrimidines occur in DNA and RNAs. Examples include 5-methyl-cytosine of bacterial and human DNA, 5-hydroxy-methylcytosine of bacterial and viral nucleic acids, and mono- and di-N-methylated adenine and guanine of... 

Adenine phosphoribosyltransferase (APRT) deficiency is an inherited disorder of purine metabolism and is inherited in an autosomal recessive manner (K18, V7). This enzyme deficiency results in an inability to salvage the purine base adenine, which is oxidized via the 8-hydroxy intermediate by xanthine oxidase to 2,8-di-hydroxyadenine (2,8-DHA). This produces crystalluria and the possible formation of kidney stones due to the excretion of excessive amounts of this insoluble purine. Type I, with virtually undetectable enzyme activity, found predominantly in Caucasians, is found in homozygotes or compound heterozygotes for null alleles. Type II, with significant APRT activity, found only in Japan, is related to a missense mu-... 

One-electron oxidation of the adenine moiety of DNA and 2 -deoxyadenos-ine (dAdo) (45) gives rise to related purine radical cations 46 that may undergo either hydration to generate 8-hydroxy-7,8-dihydroadenyl radicals (47) or deprotonation to give rise to the 6-aminyl radicals 50. The formation of 8-oxo-7,8-dihydro-2 -deoxyadenosine (8-oxodAdo) (48) and 4,6-diamino-5-formamidopyrimidine (FapyAde) (49) is likely explained in terms of oxidation and reduction of 8-hydroxy-7,8-dihydroadenyl precursor radicals 47, respectively [90]. Another modified nucleoside that was found to be generated upon type I mediated one-electron oxidation of 45 by photoexcited riboflavin and menadione is 2 -deoxyinosine (51) [29]. The latter nucleoside is likely to arise from deamination of 6-aminyl radicals (50). Overall, the yield of formation of 8-oxodAdo 48 and FapyAde 49 upon one-electron oxidation of DNA is about 10-fold-lower than that of 8-oxodGuo 44 and FapyGua 43, similar to OH radical mediated reactions [91]. 

Hydroxy-perhydropyrimido[2,Tr-][l,4]oxazine condensed into the pentacyclic compound 319 on heating in aqueous solution. The 9-OH-9-Me analogue did not undergo this reaction < 1996H(43) 1991 >. 7,8-Diamino-3,4-dihydro-277-pyrimido[2,1 -b [ 1,3]thiazin-6-one and 8,9-diamino-3,4-dihydro-2/7,6/7-pyrimido[6, -b][ 1,3]thiazin-6-one when reacted with benzamidine. HC1 in a melt at 220 °C in the presence of anhydrous NaOAc formed the purine derivatives 320 and 321, respectively <1996JME2529>. 

Some of the impetus for studying tautomeric equilibria in heterocycles arises because of the postulate that point mutations in genetic material may be introduced when a given base exists in a tautomeric form during replication [279, 305-307], Cytosine, in particular, has imino and hydroxy tautomers that are within 3 kcal/mol of the global minimum illustrated above (because of the very large number of possible tautomers for the purines and pyrimidines, only the lowest energy tautomers are presented). This analysis has been made based on a... 

Methylation of some form of 6-mercaptopurine in man has been established by the identification of 6-(methylsulphinyl)-8-hydroxypurine (LXV), 6-(methylthio)uric acid (LX), and 6-(methylthio)-8-hydroxy-A -glucuronide (LXVll). The oxidation of 6-(methylthio)purine to 6-(methylthio)-8-hydroxy-purine (LXVl) is mediated much more rapidly by rabbit liver aldehyde oxidase than by xanthine oxidase, and the oxidation is not inhibited by 4-hydroxy-pyrazolo [3, 4-d] pyrimidine [269], which is known to be an effective inhibitor of xanthine oxidase, and consequently, of the oxidation of 6-mercaptopurine [12,268]. 

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