4 -substituted nucleoside synthesis

Pyrido[3,4-d]pyrimidine-2,4-dione synthesis, 3, 215 Pyridopyrimidines, 3, 201 iV-alkylations, 3, 206 biological activity, 3, 260-261 1-electron reductions, 3, 207 IR spectra, 3, 204 mass spectra, 3, 204 MO calculations, 3, 204 NMR, 3, 202, 203 nucleophilic substitution, 3, 213 8-nucleosides synthesis, 3, 206 physical properties, 3, 201-205 protonation, 3, 206 radical reactions, 3, 215 reactions with water, 3, 207 reduced... 

This synthesis appears to be quite general for the preparation of 1-substituted nucleosides and was used with small modifications for the synthesis of l-ribofuranosyl-6-azathymine and 2 -deoxyribo-furanosyl-6-azauracil and -6-azathymine. In the case of 2 -deoxy-ribofuranosyl a mixture of a- and )8-anomers is produced, their ratio depending on the reaction conditions. In the preparation of 2 -deoxy-ribofuranosyl-6-azathymine only one anomer was obtained having probably the )8-configuration, ... 

Synthesis of 2 -/i-Fluoro-Substituted Nucleosides by a Direct Approach ... 

Reductions with LAH are frequently applied to natural product synthesis to yield the more-substituted alcohols. Some recent examples are given in equations (12) and (13). In the nucleoside synthesis, the adenosine group can tolerate the reduction conditions. 

Zinc-mediated Barbier-t) e addition of 238, followed by Luche s procedure obtained a mixture of the homoallylic alcohol diastereomers 239 and 240. Alcohol 239 was carried through benzoylation, deketalization, silylation, and ozonolysis, to produce C-branched y-lactone 241. Benzoylation of 240 followed by hydroboration, PCC oxidation, debenzoylation, and alkaline-promoted cyclization directly formed C3-branching 2-deoxyfuranose 242 [87] (O Scheme 63). A novel method for stereoselective synthesis of 4 -a-carbon-substituted nucleosides, through epoxidation of 4, 5 -unsaturated nucleosides and SnCU-promoted epoxy ring opening, was... 

An improved protocol for the efficient conversion of inosine into its 3 -phosphoramidite synthons for solid-phase oligonucleotide synthesis has been described. This procedure, which almost doubled the literature reported overall yields starting from inosine, was optimized for scale-up to multigram quantities. The portion-wise addition of DMT-Cl to a solution of inosine in DMSO and pyridine prevented multiple-site protections, which was also reported to occur in the presence of DMAP or triethylamine. Treatment with TBDMSCl in the presence of silver nitrate and pyridine in THF offered a mixture of the 2 - and 3 -substituted nucleosides from which the 5 -0-dimethoxytrityl-2 -0-tert-butyl-dimethylsilyl-protected inosine was crystallized in ethyl acetate. The mother liquor was enriched with the 2 -isomer by treatment with triethylamine in methanol. Standard conditions for phosphitylation were then applied to yield... 

Recently, C-nucleoside synthesis by glycosyl free radical coupling with protonated nitrogen heterocycles started to gain impetus. Thus, photoirradiation of the l-(2,5-anhydro-D-allonoyloxy)pyridine-2-thione derivative 798 gave the D-ribofuranosyl free radical 799 that couples with substituted pyridines to give a mixture of the two anomers of 2-pyridyl C-nucleosides... 

More recently, this group has incorporated these and related porphyrin-substituted nucleosides into tetranucleotides using standard solid support techniques to assemble chiral homo- and heteroporphyrinic arrays 38a-c. In this way, the composition and the physical properties of the array can easily be made to order simply by programming the DNA synthesis on an automated DNA synthesizer. The tetranucleotides were then able to form duplexes with the complementary strands (e.g. tetra-adenosine dA4 39). It was shown that the porphyrin electronic ground state environment is not particularly influenced by the presence or absence of the complementary strand, but the fluorescence intensity is decreased. CD measiuements confirm the helical nature of the duplexes. 

Recent methods for the synthesis of nucleoside derivatives which have been tested for anti-HIV activity, or which, because of their structure, may be good candidates for testing are described. The nucleoside derivatives considered in this review are 3 -azido-2, 3 -dideoxynucleosides, 2, 3 -dideoxy-3 -fluoronucleosides, 2, 3 -dideoxy-3 -C-substituted nucleosides, 2, 3 -dideoxy-P-D-glycero-pent-2-enofuranosyl nucleosides, 2, 3 -dideoxynucleosides and carbocyclic, acyclic and C-nucleosides. Structure-activity relationships are also considered. 

The approach to nucleoside synthesis developed by Ogura et al. (Heterocycles, 911, 8, 125, and earlier references), which involved the reaction of glycosyl isothiocyanates with substituted hydrazines to give thiosemicarbazides which were cyclized with NBS, and finally desulphurized to give the required heterocycle, has now been applied to the synthesis of pyrazolopyrimidine nucleosides derived from D-glucopyranosyl, D-arabinopyranosyl, and d-ribofuranosyl isothiocyanates. Syntheses of nucleoside analogues from reactions of glycosyl isothiocyanates with amino-acids, enamines, and diamines have been summarized. ... 

A number of -acyl- and thioureido-derivatives of 3 -amino-3 -deoxythymidine have been prepared. 1 0 Michael addition of phthalimide to enal (81) was used in the synthesis of the 3 -amino-2 ,3 -dideoxyhexo-furanose nucleosides (82) (all four isomers, R=H, Me, halogen),191 and a similar enal prepared by mercuric-ion catalysed hydrolysis of L-rhamnal was used in the same way to make the L-acosaminyl nucleoside (83) and its -anomer, and the L-ristosaminyl systems (epimers at C-3 ). 2 Michael addition of 1,2,4-triazole to (81) led, after base-sugar condensation, to the triazolyl-substituted nucleosides (84, B=T, U), together with the analogous hexopyranose systems. 93 xhe imidazolyl nucleosides (85) can be made by reaction of 3 -amino-3 -deoxythymidine with l,4-dinitroimidazoles, 9 whilst the unsaturated imidazole nucleoside (87) was made by treating the phenylselenone (86) (see Section 6) with imidazole. 195... 

The synthesis of purine and pyrimidine 2 -deoxynucleosides from a 1,2-dithio-sugar precursor is noted in Chapter 21, which also refers to the alkylation of seleno- and thio-substituted nucleosides using a mixture of a dialkyl disulphide (or diselenide) and tributylphosphine in DMF. Other thio-sugar derivatives are mentioned in Chapter 12. 

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