Purine nucleosides, fluoro

Purine, 2,6-dithioxo-1,2,3,6-tetrahydro-dethiation, 5, 558 Purine, 8-ethoxy-synthesis, 5, 577, 596 Purine, 6-ethoxycarbonylmethyl-nucleoside synthesis, 5, 561 Purine, 8-ethoxy-7-methyl-synthesis, 5, 577 Purine, 9-ethyl-synthesis, 5, 593 Purine, 6-fonnyl-reactions, 5, 547 synthesis, 5, 593 Purine, 8-fonnyl-reactions, 5, 547 Purine, 2-fluoro-synthesis, 5, 597 Purine, 6-fluoro-alkylation, 5, 529 synthesis, 5, 563, 573 Purine, 6-fluoro-9-methyl-reactions, with ammonia, 5, 562 Purine, 6-furfurylamino- — see Kinetin Purine, 9-glycofuranosyl-synthesis, 5, 572 Purine, 2-glycosyl-synthesis, 5, 587 Purine, 8-glycosyl-synthesis, 5, 585 Purine, 9-glycosyl-synthesis, 5, 572 Purine, 8-halo-synthesis, 5, 598 Purine, 2-hydrazino-synthesis, 5, 593 Purine, 8-o -hydroxyethyl-synthesis, 5, 574... 

The susceptibilities of some of these fluorinated purine nucleosides to the action of enzymes are now described. In contrast to the inertness of the 2 -deoxy-2 -fluoro- and 3 -deoxy-3 -fluorocytidine analogs 739, 744, and 821 towards cytidine deaminase, the adenosine compounds 867, 883, and 906 are readily deaminated - by the adenosine deaminase in erythrocytes and calf intestine, but the resulting (deaminated) inosine compounds (from 867 and 883), as well as 888, are highly resistant - to cleavage by purine nucleoside phosphorylase (to give hypoxanthine base for the first two). The reason was discussed. Both 867 and 883 can form the 5 -triphosphates, without deamination, in human erythrocytes or murine sarcoma cells in the presence of 2 -deoxycoformycin, an adenosine deaminase inhibitor, but... 

Synthesis of 2 -Deoxy-2 -a-fluoro Purine Nucleosides via Nucleophilic Substitutions at the Carbon-2 Position... 

The synthesis of 2 -deoxy-2 -a-fluoro purine nucleosides via cleavage of purine O-cyclo-nucleosides (see Scheme 7.2) has not been reported, presumably for the following reasons [18] (i) the synthesis of purine O-cyclonucleosides is not so easy as that of pyrimidine O-cyclonucleosides (ii) the glycosyl bond of purine nucleosides is rather unstable under severe reaction conditions such as the use of HF and (iii) it is not easy to remove the... 

Izawa, K., Torii, T., Onishi, T. and Maruyama, T. (2007) The synthesis of an antiviral fluorinated purine nucleoside 3 -a-fluoro-2, 3 -didcoxyguanosine. Current Fluoroorganic Chemistry, ACS Symposium Series 949, pp. 363-378. 

Krzeminski, J., Nawrot, B., Pankiewicz, K. W. and Watanabe, K. A. (1991) Synthesis of 9-(2-deoxy-2-fluoro-P-D-arabinofuranosyl)hypoxanthine. The first direct introduction of a 2 -P-fluoro substituent in preformed purine nucleosides. Studies directed toward the synthesis of 2 -deoxy-2 -substituted arabinonucleosides. 8. Nucleosides Nucleotides, 10, 781-798. 

Marquez, V. E., Tseng, C. K.-H., Kelley, J. A., et al. (1987) 2, 3 -Dideoxy-2 -fluoro-ara-A. An acid-stable purine nucleoside active against human immunodeficiency virus (HIV). Biochem. Pharmacol., 36, 2719-2722. 

By modifications of known procedures, the following compounds have been prepared l-P-D-arabinofuranosylth3miine,2 -deoxy-5-(trifluoromethyl)-uridine and its a-anomer, a- and p-5-trifluoromethyl-6-aza-2 -deoxyuri-dlnes,l-p-D-arabinofuranosyl-5-fluorouracil,5-fluoro-2 deoxycyti-dine,24 3 -deoxynucleosides of pyrimidines, pyrimidine and purine nucleosides of D-glucuronlc acid, 9-D-mannofuranosyladenlne, 3-P-D-ara-... 

The aza-C-nucleosides 149 pC = H, NH2) are potent inhibitors of purine nucleoside phosphorylase. These compounds, termed immucillins , have been prepared from the acetonitrile derivative 148, which could itself be made by addition of lithiated acetonitrile to the cyclic imine. Various 5 -deoxy-, 5 -deoxy-5 -fluoro-, and 2 -deoxy-analogues were also prepared. ... 

Aim of this research was to increase efficiency of producing T. thermophilus PyrNPase in cells of genetically engineered E. coli strain by optimizing the structure of the respective translated mRNA and to investigate enzymatic synthesis of purine 3 -fluoro-3 -deoxy- and 3 -fluoro-2, 3 -dideoxynucleosides possessing antiviral and cytostatic activities from the available pyrimidine nucleosides engaging tandem reactions in the presence of recombinant nucleoside phosphorylases [8],... 

Some 4, S -unsaturated-S -fluoroadenosine nucleosides are described in Chapter 20 as well as some purine nucleosides containing the 2 -deoxy-2 fluoro- -D-arabinofuransoyl moiety. A number of dideoxymonofluoro- and dideo difluoro-a-D-glucopyranosyl phosphates have been prepared in order to study their relative rates of acid hydrolysis. The synthesis of a fluorinated 3-deoj -D-glyceric add phosphonate is discussed in Chapter 17 and the conversion of a l,3-anhydro-2-deojty- 2,2-difluoro-D-hexose derivative into a hydrolytically stable thromboxane A2 mimic is covered in Chapter 24. 

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,... 

The introduction of a 2-fluoro substituent through reaction with an electrophilic fluorine source was achieved following the synthesis of 2-tributylstannyl derivatives of purine nucleosides [16] (Scheme 4). Xenon difluoiide was nsed as the fluorinat-ing reagent, and the method was compatible with the presence of alkenes in the substrate, as well as 6)-silyl and acetonide protecting groups, and with amine substitution of the purine [16-18],... 

Solid phase combinatorial synthesis is also applicable to purine nucleosides, as exemplified by the preparation of a library of more than five hundred 2,8-disubstituted guanosine analogues using SNAr displacement of the 2-fluoro group in the protected nucleoside 28, linked to the polystyrene resin with a methoxytrityl group through the ribose C-5 hydroxyl [54] (Scheme 12). The SnAt reactions were successful with primary or secondary alkylamines, but not with anilines or other arylamines. 

Scheme 20 Examples of the 6-chloro-amino-fluoro displacement sequence on purines and purine nucleosides...

Fig. 2 Examples of 6-fluoro- and 6-trifluoromethyl purines and purine nucleosides discussed in the text...

Gerster JF, Robins RK (1966) Purine nucleosides. XIII. The synthesis of 2-fluoro- and 2-chloroinosine and certain derived purine nucleosides. J Org Chem 31 3258-3262... 

Parker WB, Allan PW, Hassan AEA, Secrist JA, Sorscher EJ, Waud WR (2003) Antitumour activity of 2-fluoro-2 -deoxyadenosine against tumours that express Escherichia coh purine nucleoside phosphorylase. Crmcer Gene Ther 10 23—29... 

Liu J, Robins MJ (2007) S Ar displacements with 6-(fluoro, chloro, bromo, iodo, and alkylsulfonyl)purine nucleosides synthesis, kinetics, and mechanism. J Am Chem Soc 129 5962-5968... 

Ghosh AK, Lagisetty P, Zajc B (2007) Direct synthesis of 8-fluoro purine nucleosides via metalation-fluorination. J Org Chem 72 8222-8226... 

Recently, the synthesis and biological evaluation of acid stable 2 -6-fluoro purine dideoxynucleosides as active agents against HIV have been reported Since it was established that introduction of fluorine to the 2 -6-position of nucleosides decreases chemical and phosphorylase (PNP) catalyzed hydrolysis in general and for purine nucleosides in particular (1, Figure 1), these 2 -fluoro analogues were designed to overcome the chemical and metabolic instability of the parent purine dideoxynucleosides. 

In this paper we wish to report some new approaches to the synthesis of 2 -fluoro- and 3-fluoro-substituted purine nucleosides, which may stimulate further progress in this area. 

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