Aminopurine nucleoside

The 2 -deoxy-0 -(pentafluorophenyl)guanosine 11 can be used as a synthon for the preparation of 6-substituted 2-aminopurine nucleosides, e.g. 12. ... 

Treatment of aminopurine nucleosides with nitrous acid in aqueous solution normally results in replacement of the amino group by a hydroxyl group thus, inosine is prepared from adenosine. Although this process is undoubtedly a diazotization, the intermediate diazonium salt must have... 

Diazotization of 2-aminopurine nucleosides under non-aqueous conditions has been utilized to introduce fluorine, chlorine, and bromine into the 2-position. ... 

A series of 8,5 -cyclo-8-aminopurine nucleosides has been synthesized from the 8-bromo-5 -0-tosyl nucleoside (62) illustrated in Scheme 7 for the adenosine analogue. ... 

V. Nair and S.D. Chamberlain, Reductive deamination of aminopurine nucleosides. 

Gaied NB, Glasser N, Ramalanjaona N, Beltz H, Wolff P, Marquet R, Burger A, Mly Y (2005) 8-vinyl-deoxyadenosine, an alternative fluorescent nucleoside analog to 2 -deoxyribosyl-2-aminopurine with improved properties. Nucl Acids Res 33 1031-1039... 

A one-pot procedure for the transformation of 6-thiopurine nucleosides to 6-aminopurines was developed using DMDO as the oxidant in the presence of a stoichiometric amount of various amines <1996T6759>. For example, 6-thio-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)purine was readily converted to the 6-alkylamino derivatives (6-amino, 75% yield 6-methylamino, 55% yield). Similarly, A -6-acetyl-8-thio-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)adenosine was converted to A -6-acetyl-8-methylamino-9-(2, 3, 5 -tri-0-acetyl-/3-D-ribosyl)adenosine (DMDO, methylamine, CH2CI2, 25 °C, 83% yield). Less nucleophilic 2-mercaptopurine derivatives did not undergo the displacement reaction, however, and only the products of dithiane formation and desulfurization were isolated. 

The existence of two separate enzymes in animal tissues responsible for the liberation of ammonia from each of the two aminopurines, adenine and guanine, the latter specific for the free purine and the former for the nucleosides, was initially presented by Jones and his colleagues 11, 12). In 1928, Schmidt 13-15) demonstrated that AMP aminohy-drolase was responsible for the appearance of inosinic acid in muscle and for at least a portion of ammonia liberated during contraction. He showed not only a marked specificity for deamination of 5 -AMP but also provided the first clue that muscle adenylic acid (5 -AMP) and yeast adenylic acid (3 -AMP) were different compounds. Initial evidence for guanine and adenosine aminohydrolase including aspects of the specificity were also described by Schmidt 16). Additional details regarding development of interest in purine aminohydrolases are available in several excellent reviews 17-20). 

Fig. 15.1. The four bases found in the nucleic acids. Uracil occurs in RNA and is substituted by the analogous thymine (5-methyluracil) in DNA. Uracil is the keto tautomer of 2,4-dihydroxy pyrimidine with two donors N(1)H, N(3)H and two acceptors 0(2), 0(4). Cytosine is the keto tautomer of 4-amino, 2-hydroxy pyrimidine with three donors N(4)H2, N(1)H and two acceptors 0(2), N(3). Adenine is 6-aminopurine with three donors N(6)H2, N(9)H and three acceptors N(l), N(3), N(7). Guanine is the keto tautomer of 2-amino, 6-hydroxy purine with three donors N(2)H2, N(9)H and three acceptors, N(3), N(7), 0(6). In the nucleosides, pyrimidine N(l) and purine N(9) are substituted by ribose or deoxyribose (see Fig. 17.1)...

The bases found in RNA (ribonucleic acid) are the purine heterocyclics adenine (6-aminopurine) and guanine (2-amino-6-oxypurine) and their complementary pyrimidine bases uracil (2,4-dioxypyrimidine) and cytosine (2-oxy-4-aminopyrimidine), respectively (Section 1, Appendix). In RNA double-stranded duplexes adenine (A) base-pairs with uracil (U) via two hydrogen bonds (A=U) and guanine base-pairs with cytosine (C) via 3 hydrogen bonds (G=C). Adenine forms the nucleoside adenosine by an N-glycosidic link with the... 

In addition, ADA has also been used in the resolution of some nucleoside analogs derived from 6-aminopurines [40]. In this context, an interesting example is shown in Scheme 10.18. This strategy has been successfully developed for carrying out the resolution of ( )amino compound under different reaction conditions allows the preparation of (-i-)-carbovir, which is less active as an HSV-1 inhibitor than the leva enantiomer (Scheme 10.18) [41],... 

Tables 48 and 49 give additional examples of the formation of aminopurines formed by displacement reactions on halopurines. Table 48 shows reactions on simple purines, Table 49 on nucleosides.

Replacement of the amino group in aminopurines by halogens has been achieved in several ways. Thus 2,6-diamino-9-[(2,3,5-tri-0-benzyl)-D-arabinofuranosyl]purine with fluoroboric acid and sodium nitrite in THF at -10 gave a 48% yield of the 2-fluoro-adenosine derivative (186 R = 2,3,5-tri-0-benzyl-/S-D-arabinofuranosyl) (79JHC157), and similar use of 2,6-diamino-9-j8-D-ribofuranosylpurine in hydrochloric acid solution gave the 2,6-dichloropurine nucleoside (187) (60JA463). 

Derivatives of 6-(2-substituted vinyl)-2-aminopurine have been incorporated into oligonucleotides using the phosphoramidite reagent 200. The free nucleoside has been demonstrated to cross-link with cytidine and guanosine. 

Initial studies were made with purine in methanol exposed to shortwave (>250 nm) UV light, - the photo product being derived from addition of the alcohol across the 1,6-double bond. This work was later extended to purine nucleoside (nebularine) and 2-aminopurine and the use of other... 

Because several reports had indicated that polymerases would incorporate 8-aminopurines as well as derivatives of aminoallyl-dUTP, Perrin s choice of modified dNTPs was based on synthetic expediency while the aminoallyl-dUTP was readily prepared, and became commercially available in the mid-1990s, the 8-histaminyl-dATP was unknown. Bromination of dAMP followed by displacement with histamine and triphosphorylation readily afforded the 8-histaminyl-dATP for study. Nevertheless, it was unknown whether both nucleosides could be copolymerized to any extent. Indeed, PCR, which haltingly incorporated the aminoallyl-dUTP, failed to incorporate the 8-histaminyl-dATP to any extent, and no amplicon was observed when both modified dNTPs were used in lieu of their unmodified congeners. 

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