2- Fluoroadenosine

Several analogues of adenine or adenosine are reported to be incorporated into nucleic acids 2-fluoroadenosine [342], tubercidin [190, 192, 342a], toyacamycin [193,342a], sangivatnycin [342a, b], cordycepin [168,343,344], 4-aminopyrazolo[3, 4-d] pyrimidine [119], formycin [344a], and 9- -D-arabinofuranosyladenine [152, 154], The evidence for the incorporation of 9-(3-D-arabinofuranosyladenine has been questioned [345]. 

The same conditions led to decomposition in an attempt to prepare 2 -deoxy-2-fluoroadenosine from 2 -deoxyadenosin-2-amine. The reaction was successful when applied to 3, 5 -di-0-acetyl-2 -deoxyadenosin-2-amine giving the 2-fluoro derivative 2. ... 

Maruyama, T., Utzumi, K., Sato, Y. and Richman, D. D. (1994) Synthesis and anti-HIV activity of 2-substituted 2 -deoxy-2 -fluoroadenosines. Nucleosides Nucleotides, 13, 1219-1230. 

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-... 

Cyclic Nucleotides.—New analogues of cAMP and cGMP that have been reported include 2-fluoroadenosine 3, 5 -monophosphate, 9-/ -D-xylofuranosylguanine 3, 5 -monophosphate, 8-carbamoyl- and 8-carboxy-adenosine 3, 5 -monophosphates (prepared from 8-bromo-cAMP, using standard transformations), and a series of 2-substituted-l,A -ethenoadenosine 3, 5 -monophosphates, prepared by ring reclosure of (30), which is the product of alkaline hydrolysis of 1, N -etheno-cAMP. The last-named have useful fluorescent properties, like the parent compound. So, also, have 8-azido-l,N -ethenoadenosine 3, 5 -monophosphate (also prepared... 

Nitration of 6-substituted purines at C-2, using a mixture of tetra-n-butylammonium nitrate and trifluo-roacetic anhydride, is an exceptionally useful functionalisation of the purine ring system. The reaction works for both electron-rich (adenosine), 6-alkoxypurines and electron-poor (6-chloropurine) substrates, but full protection of all OH and NH groups is required. This is not a simple electrophihc substitution - the mechanism has been shown, using 6-chloro-9-Boc purine, to involve sequential nitration of N-7, addition of trifluoroacetoxy at C-8 and then migration of the nitro group to C-2. The final, re-aromatisation, step involves elimination of trifluoroacetic acid. Displacement of a 2-nitro group, thus introduced, by fluoride as nucleophile (see 27.5 for nucleophilic substitutions) can be made the means to synthesise 2-fluoroadenosine. ... 

Since 1976 a number of 2 -substituted 2 -deoxynucleoside 5 -diphosphates have been shown to be mechanism-based inactivators of the ribonucleotide reductases from a variety of sources (Table I). This work was extended by Stubbe and Kozarich 50, 51), who studied the reaction of several 2 -halo-substituted 2 -deoxynucleoside 5 -diphosphates with RDPR. Incubation of RDPR with CIUDP, 2 -deoxy-2 -fluoroadenosine 5 -diphosphate (FADP), or 2 -deoxy-2 -fluorocytidine 5 -diphosphate (FCDP) resulted in time-dependent enzyme inactivation, concomitant and stoichiometric loss of all substituents from the ribose moiety, increase in the UV-Vis absorbance of the protein near 320 nm, and... 

Deoxy-5-ethyluridine, E-2 2 -Deoxy-2 -fluoroadenosine, D-63 5 -Deoxy-2-fluoroadenosine, D-64... 

C-Fluoroadenosine 5 -sulfamate, N-84 2-Fluoroadenosine, F-11 8-Fluoroadenosine, F-12 Fluoroancitabine, F-19 Fluoroblasticidin S, B-39 5-Fluorocytidine, F-13 p-Fluoro-ddA, L-48 2 -Fluoro-2 -deoxyadenosine, D-63 5-Fluoro-3 -deoxycytidine, F-13 5-Fluoro-3 -deoxyuridine, F-18 8-Fluoroerythromycin, E-18 5-C-Fluorogalactosyl fluoride, F-14... 

Chloro-2-deoxyarabinose D-form Di-Et dithioacetal, C-74 2-Chloro-2-deoxyascorbic acid L-form, C-78 2-Chloro-2-deoxyglucose D-form, C-85 2-Chloro-2-deoxylyxose a-D-Pyranose-/orw, C-95 2-Chloro-2-deoxyxylose D-Pyranose-/orm, C-108 2-Deoxy-2,2-difluoro-flrfl6mo-hexose D-form, D-55 2 -Deoxy-2 -fluoroadenosine, D-63 1 -(2-Deoxy-2-fluoro- p-D-arabinofuranosyl)uracil, D-66 2-Deoxy-2-fluoroarabinose a-L-Furanose-/<3rm 1,3,5-Tribenzoyl, D-68 2-Deoxy-2-fluoroarabinose p-D-Furanose-/orm, D-68 2-Deoxy-2-fluoroarabinose a-D-Pyranose- brm, D-68 2-Deoxy-2-fluoroarabinose p-D-Pyranoae-/orm, D-68 2-Deoxy-2-fluoroarabinose D-form, D-68 2 -Deoxy-2 -fluoro-ara -aristeromycin, D-70 2-Deoxy-2-fluoroascorbic acid L-form, D-71 2 -Deoxy-2 -fluorocytidine, D-72... 

A convenient synthesis of 5 -deoxy-2-fluoroadenosine from guanosine has been reported. Ring-opening of l-(2,3-anhydro-P-D-lyxofuranosyl)-cytosine and -uracil with ammonium bromide, iodide, azide, and thiocyanate in refluxing ethanol has been used to prepare l-(3-deoxy-3-halogeno-P-D-arabinofuranosyl)-... 

PMOXA-fo-PDMS-fo-PMOXA Tsx Inosine, adenosine, guanosine, 2-fluoroadenosine Yes [59]... 

A rapid synthesis of 2 -deoxy-2 -fluoroadenosine Involves the use of DAST on a suitably protected ara-A derlvative.85 A number of purine nucleosides containing the 2 -deo3qr-2 -fluoro-p-D-arabinofuranosyl moiety (48) have been prepared from glycosyl bromide and purine bases the guanosine analogue (48,... 

Fluoropurines have also been prepared by SNAr displacement of 2-nitropurine derivatives, using tetra-A-butyl ammonium fluoride (TBAF) as the fluoride source [14], A variation on this method proved particularly useful for the introduction of an T radiolabel into 2-fluoroadenosine 10, since the Balz-Schiemann reaction is poorly applicable to radiochemistry and the displacement of 2-iodo- or 2-fluoropurines with radioactive fluoride ion is inefficient [15] (Scheme 3). 

Scheme 3 The preparation of a 2-fluoroadenosine derivative by SnAf reactions...

Montgomery JA, Hewson K (1957) Synthesis of potential anticancer agents. X. 2-fluoroadenosine. J Am Chem Soc 79 4559... 

Braendvang M, Gundersen L (2006) A novel method for the introduction of fluorine into the purine 2-position synthesis of 2-fluoroadenosine and a formal synthesis of the antileukemic drug fludarabine. Synthesis 2993-2995... 

Ohrui H, Kohgo S, Hayawaka H, Kodama E, Matsuoka M, Nakata T, Mitsuya H (2007) 2 -deoxy-4 -C-ethynyl-2-fluoroadenosine a nucleoside reverse transcriptase inhibitor with highly potent activity against wide spectrum of HIV-1 strains, favorable toxic profiles, and stability in plasma. Nucleosides Nucleotides Nucleic Adds 26 1543-1546... 

Ye S, Rezende MM, Deng W, Kirk KL (2004) Synthesis of 2, 5 -dideoxy-2-fluoroadenosine and 2, 5 -dideoxy-2,5 -difluoroadenosine. Potent P-site inhibitors of adenylyl cyclase. J Med Chem 47 1207-1213... 

Analogues of tiazofurin adenine dinucleotide (TAD) containing 2 -deoxy-2 -fluoroadenosine, 3 -deoxy-3 -fluoroadenosine and 2 -deoxy-2 -fluoro-ara-A, have been synthesized and evaluated as inhibitors of IMP dehydrogenase. ... 

For the synthesis of 2 -deoxy-2 -fluoroadenosine (2a) from ara-A, smaller 3, 5 - protecting groups (such as methoxymethyl, benzyl, or methojgrbenzyl groups) appear to be more favorable for ara-A to assume the presumably favored C-3 endo conformation than the trityl groups (which promote C-3 endo to C-2 endo conformational shift). In order to prepare 3, 5 -protected ara-A, 3, 5 -0-(l,l,3,3-tetraisopropyl)disiloxanyl-N -benzoyladenosine (54, Scheme 10) was triflylated, and the... 

We also synthesized 3 -fluoroadenosine. In our case, the starting material was again 2, 5 -di-0-trityl-N -trityladenosine 32 (Scheme 5), which had already served as the starting material for the synthesis of 2 -deoxy-2 -fluoroadenosine (2a, Scheme 11). 

---