2,8-diaminopurine

Fluoro-2, 3 -dideoxyadenosine (898), 3 -fluoro-2, 3 -dideoxyguan-osine (899) and 9-(2,3-dideoxy-3-fluoro-y -D- r> 7A/ o-pentofuranosyl)-2,6-diaminopurine (900) were synthesized by way of DAST treatment of... 

Figure 6 Acyclic nucleoside phosphonates (ANPs) 9-(2-phosphonylmethoxy-ethyl)-adenine (PMEA) and -2,6-diaminopurine (PMEDAP), (R)-9-(2-phosphonyl-methoxypropyl)-adenine (PMPA) and -2,6-diaminopurine (PMPDAP), (5)-9-(3-fluoro-2-phosphonylmethoxypropyl)-adenine (FPMPA) and -2,6-diaminopurine (FPMPDAP), and the bis(pivaloyloxymethyl) ester of PMEA [Bis(pom)-PMEA].

Balzarini J, Holy A, Jindrich J, Naesens L, Snoeck R, Schols D, De Clercq E. Differential antiherpesvirus and antiretrovirus effects of the (S) and (R) enantiomers of acyclic nucleoside phosphonates potent and selective in vitro and in vivo antiretrovirus activities of (R)-9-(2-phosphonomethoxy-propyl)-2,6-diaminopurine. Antimicrob Agents Chemother 1993 37 332-338. 

The antiviral nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine also uses its N7 as a major binding site and forms a N7-phosphonate macrochelate (698).1833 Another antiviral analogue of 2 -deoxyguanosine, acyclovir (9-[(2-hydroxyethoxy)-methyl]guanine) forms with Ni11 a bis-complex with two N7 coordinated in trans position to each other.1834... 

Even when a leaving group is present on position C-2, no addition at C-2 takes place. Another example to illustrate this behavior can be taken from the reaction of 2,6-dichloropurine with potassium amide in liquid ammonia. Besides 2-chloroadenine, 2,6-diaminopurine was obtained (81TH1). It was proved that the 2,6-diaminopurine was not formed from 2-amino-6-chloropurine but from 2-chloroadenine (Scheme 11.40A). 

Fig. 10A pL (L=H or D) profiles of hairpin ribozyme of the native sequence of and 2,6-diaminopurine at position 8 [119]. The native sequence in H2O and in D2O are represented hy filled diamonds and filled squares, respectively. 2,6-diaminopurine at position 8 in H2O and in D2O are represented by open circles and open triangles, respectively. B Proposed catalytic mechanism. RNA cleavage catalyzed by the keto-enol tautomeriza-tion of Gg is achieved by a abstraction of a proton from the N1 to the 5 -0 leaving group [119]... 

The enzymatic conversion of many analogues of the naturally occurring purines directly to their biologically active form, the ribonucleotides, in vivo [5, 8, 10, 13, 39] underlines the importance of these enzymes to the drug action of this class of compounds. 2-Aminoadenine (2, 6-diaminopurine, I) [107], 2-fluoroadenine (II) [108], 4-aminopyrazolo [3, 4-d] pyrimidine (VIll) [109]. and 2- and 8-aza-adenine (IX and X) [ 110, 111] have all been shown to be substrates for the adenine phosphoribosyltransferase [J12, 113]. Extensive studies on the metabolism of 2-aminoadenine (I) in E. coli [114, 115], L cells [116], and mice [117] have also shown its conversion by this enzyme to the ribonucleotide. 

Rajagopalan P, Gao ZL, Chu CK, Schinazi RF, McClure HM, Boudinot FD. High-performance liquid-chromatographic determination of (-)-beta-D-2,6-diaminopurine dioxolane and its metabolite, dioxo-lane guanosine, using ultraviolet and online radiochemical detection. Journal of Chromatography. B, Biomedical Applications 672, 119-124, 1995. 

To a soln of ethyl (2,6-diaminopurin-9(9H)-yl)acetate (12 7.00 g, 29.6 mmol) in dry, degassed dioxane (250 mL) was added freshly prepared IV-benzyloxycarbonyl-lV -methylimidazolium triflate (Rapoport s reagent 16.30 g, 44.5 mmol) and the reaction was stirred for 20 h. The dioxane was removed under reduced pressure and the yellow viscous oil was triturated with EtOAc/Et20 (1 4) until a solid product resulted. Crystallization (5% MeOH/EtOAc) afforded 13 yield 9.60 g (88%) mp 185-187 °C high-resolution FAB-MS m/z calcd. 371.1468 found 371.1468. 

Iminomethyl-3-methyl-6-aminomethyl-9//-purine (441) was isolated from the sea anemone Sagartia troglodytes collected in the Bay of Naples. The structure of 441 was determined by X-ray analysis. The synthetic 2,6-diaminopurine (DAP) shows a wide variety of biological activities such as inhibition of the growth of tumors, viruses, plants, or bacteria, whereas the trimethyl derivative (441) shows considerably less inhibitory capacity than DAP (358). A new purine, 1,3,7-trimethyl-guanine (442), was isolated... 

Because of the potential source of error just noted, it is advisable to have independent confirmation of Kohs in the absence of Mg2+. For the A-riboswitch RNA, moderate concentrations of the most tightly binding ligand (2,6-diaminopurine) do in fact stabilize the native structure to some degree at 20 °C from the melting experiments used to generate Fig. 21.4B,... 

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