Nucleosides pyrimidine anhydro

Despite the fact that secondary hydroxyl groups of nucleosides also react with 23 (see later), selective iodination of only the primary hydroxyl group in some unprotected, pyrimidine nucleosides can also be achieved.82 Thus, brief treatment of thymidine with 1.1 mol-equivalents of 23 in N,N-dimethylformamide gave crystalline 5 -deoxy-5 -iodothymidine in 63% yield. It was even possible to effect some selective iodination of the 5 -hydroxyl group of 2,2 -anhydrouri-dine without excessive cleavage of the (quite labile) anhydro linkage. 

The studies of Levene and LaForge60 on the nitration of uridine have since been re-investigated. It had been reported, several decades ago, that treatment of uridine with nitric acid produced a Nitro-Uridin-Carbon-saure which was stated to be a dimer containing an anhydro typeof linkage (positions unspecified) between two nucleoside residues.60 According to an abstract,269 this compound has now been identified as the monomeric 5-ni-tro-l-(/8-D-ribosyluronic acid)uracil (CXXII) this was converted to the isopropyl ester and the 2,3-O-isopropylidene acetal thereof. Nitration of the pyrimidine moiety of uridine without oxidation of the 4-(hydroxy-... 

The preferred reaction of pyrimidine nucleoside 5 -aldehydes with diethylaminosulfur trifluoride is the formation of the (7, 5 -anhydro-5 -fluoronucleosidc 11. Substitution at N3 leads to the 5. 5 -difluoro derivative 12. ... 

Monaharan has developed a versatile synthetic route for the synthesis of 2 -0-[(N, iV-dimethylamino)-oxyethyl] modified purine and pyrimidine nucleoside phosphoramidites (63a-d) to be used as antisense oligonucleotide building blocks. In the syntheses of the purine-based analogues, the (iV, N-dimethylamino)-oxyethyl group was introduced via a 2 -allyloxy nucleoside intermediate, while the pyrimidine-based nucleosides were obtained from the TBDMS-protected 2,2 -anhydro-5-methyluridine via ring opening reaction in the presence of borane and ethylene glycol. The aminoxy derivatives were... 

Hirata, M, Studies on nucleosides and nucleotides. IX. Nucleophihc substitution of secondary suEonyloxy groups of pyrimidine nucleosides. II. Reaction of 2,2 -anhydro-l-(3 -0-tosyI-p-D-arabinofuranosyI)uraciI with sodium bromide, sodium ethanethiol and sodium azide, Chem. Pharm. Bull, 16, 291-295, 1968. 

Oxoformycin B (388), the catabolite of formycin and formycin B, was synthesized before the parent nucleosides in 1970 from the 2,5-anhydro-l-ureido-D-allitol derivative 416. Compound 416 was used to build the 4,5-dimethoxycarbonylpyrazol-3-yl C-nucleoside 419, followed by construction of the fused pyrimidine ring as shown in Scheme 117. Selective amidation of the ester function at C5, rather than that at C4, is a key step during this... 

Anhydro-D-allonodithioate (512) reacted with 2-hydrazinopyrimi-dine to form the l,2,4-triazolo[4,3-fl]pyrimidin-3-yl C-nucleoside 567 as an intermediate that underwent thermally induced Dimroth-like rearrangement to the l,2,4-triazolo[l,5-fl]pyrimidin-2-yl C-nucleoside 568 (89MI5) (Scheme 150). 

For pyrimidine nucleosides, the ease of anhydro-ring formation by intramolecular displacement is in the order 2,2 > 2,3 > 2,5. An-hydrocytidine derivatives are formed more readily than the corresponding anhydrouridines, and N4-acylation further enhances the nucleophilicity of the cytosine residue.419 N-Acyl-2,2 -anhydro-1 -/3-D-arabinofiiranosylcytosines are also more susceptible to hydrolysis at pH 7 than either 2,2 -anhydrouridine or 2,2 -anhydrocytidine. The product isolated after p-toluenesulfonylation of a mixture containing N-acetyl-3 -5 -di-0-acetylcytidine (146) was N-acetyl-l-(3,5-di-0-acetyl-/3-D-arabinofuranosyl)cytosine (149). The 2 -O-p-tolylsulfonyl intermediate (147) presumably cyclizes, to give the 2,2 -anhydride (148), which is rapidly hydrolyzed419 to 149. 

Numerous syntheses have also been reported for arabinofuranosyl nucleoside analogues, prepared either conventionally from arabinofuranosyl derivatives or via 2,2-anhydro-nucleosides obtained from appropriate ribonucleosides. 5-Aza-cytosine-D-arabinoside has been synthesized and found to show similar antiviral activity to Ara-C(arabinosyl-cytosine). 7-a-, 7-<3-, 9-0 -, and 9- 3-arabino-furanosyl derivatives of 3-deazaguanine have also been prepared, but none showed any anti-tumour activity. 9-(o -D-Arabinofuranosyl)-8-aza[2- C]-adenine, 7-(/3-D-arabinofuranosyl)-pyrrolo[2,3-d]pyrimidine-4(3//)-one (15)," l-(a-D-arabinofuranosyl)- and l-(/3-D-xylofuranosyl)-4-nitropyrazole, and Ot-arabino-nucleosides of 5-fluoro-cytosine and -uracil derivatives have also been prepared. An improved synthesis of 9-(/3-D-arabinofuranosyl)-2-fluoro-adenine has been reported. The ratio of o to 3 anomers obtained by phase-transfer reaction of 2,3,5-tri-O-benzyl-D-arabinofuranosyl bromide with 6-chloro-2-thiomethyl-7-deazapurine varied with the quaternary ammonium salt used as a catalyst, although the jU-anomer predominated in every case. 2,2-Anhydro-nucleosides have been used to prepare l-j3-D-arabinofiiranosyl derivatives of 5-alkylthio-uracils, 5-ethyl-cytosine, and 5-ethyl-uracil, 8-alkylamino-purines, and 2-aralkylamino-l,4-dihydro-4-imino-pyrimidine hydrochlorides (16). ... 

Addition of the anion derived from uracil to l,5 2,3-dianhydro-4,6-0-benzyli-dene-D-allohexitol, followed by inversion of configuration of the resulting 3-OH group by displace,ment of its mesylate derivative with sodium hydroxide, afforded 12. Compound 12 was a useful intermediate for making l,5-anhydro-2-deoxy-D-mannitol-containing pyrimidine nucleoside analogues. ... 

Ag-acetate added to a soln. of 5 -deoxy-5 -iodo-3 -0-mesylthymidine in methanol, stirred and refluxed 0.5 hr. 2,5 -anhydro-l-(2-deoxy-3-0-mesyl-y -D- ry /zro-pentofuranosyl)thymine (Y 67%) allowed to react 5 days at room temp, with liq. NHg in a glass-lined steel bomb -> 2,3 -imino-l-(2-deoxy-y -D-r/zr o-pento-furanosyl)thymine (Y 84%). I. L. Doerr, R. J. Cushley, and J. J. Fox, J. Org. Chem. 33, 1592 (1968) pyrimidine nucleoside transformations via anhydronucleosides, review, s. Pure Appl. Chem. 28, 223 (1969). 

Reductive cleavage (triethylsilane-trimethylsilyl triilate) of the isopropylidene derivatives 17 gives anhydro-sugars 18. The OH-2 groups in 18 have been further converted to mediates and displaced with purine bases or azide (further converted into a pyrimidine ring) to lead to nucleoside analogues. ... 

Cytidine has been converted into l-(5-amino-5-deoxy-j8-D-arabinofuranosyl) cytosine by a sequence of reactions involving A-benzoylation, sulphonation, acetylation, displacement with azide ion, e/c., and l-(3-amino-3-deoxy-jS-D-arabinofuranosyl)-6-azauracil was derived from 2, 3 -di-0-methanesulphonyl-5 -O-trityl-6-azauridine via 2,2 - and 2, 3 -anhydro-nucleosides. Other syntheses have been accomplished by the condensation of an appropriately derivatized amino-sugar with either a pyrimidine or purine derivative for example, the Hilbert route was used to prepare l-(2-amino-2-deoxy-a-D-arabino- and -jS-o-xylo-furanosyl)cytosine. > The reactivity of l,3,4,6-tetra-0-acetyl-2-acyl-amido-2-deoxy-j3-D-glucopyranoses in condensation reactions with 2,6-dichloro-purine, theophylline, and 6-benzylaminopurine was shown to be in the order benzamido > acetamido > phthalimido. 9-(3-Acetamido-2,5-di-0-acetyl-3-deoxy-j8-D-ribofuranosyl)-2,6-dichloropurine has been synthesized and converted into the corresponding 2,6-diamino- and 6-amino-2-chloro(fluoro)-nucleosides. ... 

Pyrimidine nucleosides have been converted directly into 2,2 -anhydro-nucleosides by the action of 2-acetoxybenzoyl chloride in refluxing acetonitrile. ... 

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