4 -Azido-2 -deoxyadenosine

The cytidine and inosine analogues in the 4 -azido-2 -deoxy series were made by well known procedures from the uridine and adenosine analogues, respectively (Scheme II). Thus, following the method of Reese, 4 -azido-2 -deoxyuridine was acetylated and then converted to the 4-triazolide, which on treatment with ammonium hydroxide furnished 4 -azido-2 -deoxycytidine. Using a procedure of Herdewijn, 4 -azido-2 -deoxyadenosine was enzymatically deaminated to the inosine analogue. 

Additional information <1> (<1>, the deletion mutants rDm-dNKAClO and rDm-dNKAC20 show the same substrate activity pattern as the recombinant wild-type enzyme. Relative phosphorylation of 2 -deoxycytidine and 2-chloro-2 -deoxyadenosine increases with increasing C-terminal truncation. The relative activities of rDm-dNKAClO and rDm-dNKAC20 with deoxyribonucleosides remains largely unchanged, whereas there is a substantial decrease in the phosphorylation of the purine ribonucleosides adenosine and guanosine, as well as of all dideoxyribonucleosides and 3 -azido-2 ,3 -dide-oxythymidine. The relative activities with the pyrimidine ribonucleosides and l-/l-D-arabinofuranosylcytosine and l-/i-D-arabinofuranosylthymine are not affected by the C-terminal deletions [4]) [4]... 

The Friedel-Crafts condensation is also useful for the synthesis of deoxynucleosides, e.g. 3 -azido-3 -deoxyadenosine. Recently, (3,(V-bis(trimethylsilyl)acetamide, instead of hexa-methyldisilazane (HMDS), has been used for the silylation. A, 7V-Bis(trimethylsilyl)acetamide does not introduce chemically interactive side products and has been found to be superior as a silylating agent, especially for one-pot reactions. ... 

Numerous azido-substituted nucleosides have been evaluated as potential antitumour agents. De Clercq et al. found that of a series of 2 - and 3 -azidonucleoside analogues prepared and evaluated for antitumour activity against murine LI210 cells in vitro, the most potent derivative was 3 -azido-2, 3 -dideoxyadenosine (146), with 3 -azido-2, 3 -dideoxyguanosine (102), 3 -azido-3 -deoxyadenosine (147) and 2 -azido-2 -deoxycytidine (148) proving moderately active [170], the activity of the last compound having been reported previously [171, 172], AZT was also evaluated in this study... 

The majority of newly reported nucleoside 5 -monophosphates have been prepared using phosphorus oxychloride in trialkyl phosphate solution. These include the monophosphates of 2-fluoroadenosine, 2-amino-6-chloro-9-(/S-D-ribofuranosyl)-purine, bredinin (6), cordycepin 2 -azido-2 -deoxyadenosine, 2 -fluoro-... 

The synthesis of the two diastereoisomers of P -l-(2-nitrophenyl)ethyl adenosine S -lri-phosphate (91) has been achieved using resolved (R)- and (5)-l-(2-nilroidienyl)ethanol. The alcohols were converted to (R)- and (5)-l-(2-nitrophenyl)ethyl phosphates by phosphitylation with N,)V-diisopropyl-fi(s-(2-cyanoethyl)phosphoramidite (92) and subsequent oxidation with 3-chlorobenzoic acid. Each of the monophosphates was activated with carbonyidiimidazole and condensed with adenosine diphosphate to give the desired triphosphate. These ATP analogues can be used for the rapid release (by flash photolysis) of ATP in biological systems. The 8-azido-3 -0-anthraniloyl derivatives of 2 -dADP (93) and 2 -dATP (94) have been prepared in seven steps from 8-azido-2 -deoxyadenosine. These compounds are of interest as fluorescent and photoactivatable probes for the nucleotide binding site of kinases and cyclases. In particular, (94) was shown to be a competitive inhibitor of Bordetella pertussis adenylate cyclase and the observed K- (74 pM) was close to tiiat predicted from the K- value of 3 -0-anthraniloyl-2 -dATP. ... 

Oligonucleotides containing the photoreactive nucleosides, 2-azido-2 -deoxyi-nosine and 8-azido-2 -deoxyadenosine, have been prepared. ... 

Syntheses involving standard condensation procedures for heterocyclic bases with amino-sugar derivatives have included the preparation of 2 -azido-, 3 -azido-2 ,5 -diazido-, and 3, 5-diazido-derivatives of arabino-nnAinc, 3 -amino-3-deoxy-adenosine, -uridine, and -cytidine 5-phosphates, 2, 3-bis(2-chloroethyl)-aminophosphoryl-3-amino-3-deoxyadenosine (which has anti-tumour activity), 3-A -methyl-A -nitrosoureido-3-deoxy-adenosine and the corresponding 5-substituted isomer, and 2 -azido-2-deoxy- and 2-amino-2-deoxy-D-arabinofuranosyl-... 

Azaxanthosine, A-893 2 -Azido- 5-bromo-2, 3 -dideoxyuridine, A- 894 3 -Azido-5-chloro-2, 3 -dideoxycytidine, A-895 3 -Azido-5-chloro-2, 3 -dideoxyuridine, A-896 8-Azidocyclic AMP, A-897 5 -Azido-5 -deoxyadenosine, A-898 5 -Azido-5 -deoxythymidine 3"-Ac, A-915 5 -Azido-5 -deoxythymidine, A-915 3 -Azido-3 -deoxy-5 -thymidylic acid, 9CI, Z-4 l-(3-Azido-2,3-dideoxy-2-fluoro-p-D-arabinofuranosyl)thymine, A-917 2 -Azido-2, 3 -dideoxy-5-iodouridine, A-920 3 -Azido-2, 3 -dideoxy-5-methylcytidine, A-921 2 -Azido-2, 3 -dideoxy-5-methyluridine, A-922 2 -Azido-2, 3 -dideoxyuridine, A-923... 

In their initial work, these authors reported a poten-tiometric study on the ability of the Zn " " complex of cyclen (80) to interact with the deoxyribonucleotides 2 -deoxyadenosine (dA), 2 -deoxyguanosine (dG), 2 -deoxy-cytidine (dC), 2 -deoxythymidine (dT), uridine (U), and 3 -azido-3 - deoxythymidine (AZT). [Zn(80)] " had a good selectivity for dT, U, AZT, and the related derivatives Ff (ftorafur, 5-fluoro-l-(tetrahydro-2-furyl)uracil), and... 

A preparation of 3 -azido-3 -deoxyadenosine and hence 3 -amino-3 -deoxy-adenosine has been reported. ... 

Azhayev et al. (74) described the synthesis of 3 -azido-3 -deoxyadenosine and 3 -amino-3 deoxy-adenosine and 15+ intermediates with obtained using ready-for-use Silufol U Vjs4 silica gel sheets in the solvent systems chloroform-methanol (95 5), benzene-ethyl acetate (17 3), benzene-ethyl acetate (4 1) and l-butoanol-H20 (85 15). 

When the deoxyadenosine derivative (24) (Scheme 9) was treated with triflic anhydride, the configurational Inversion shown took place in good yield, presumably by intramolecular participation of the 5 -ester, This chemistry then led to a synthesis of 3 -azido-2, 3 -dldeo3yadenosine. The synthon... 

Ikehara, M., Takatsuka, Y., and Uesugi, S (1979) Polynucleotides LIII. Synthesis and properties of 2 -azido-2 -deoxyadenylyl-(3 -5 )-2 -azido-2 deoxyadenosine. Chem. Pharm. Bull. 27, 1830-1835,... 

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