Thymidine 5 -0-trityl-, reaction with

Treatment of O-benzoyl anhydrothymidine 64 (R1 =Me R2 = COPh) with MgX2 (X = Br, I) in toluene at 100 °C afforded halo-substituted thymidines 65 (Nu = Br, I) in 70-75% yields <1995NN307, 1995TL873>. Alkylation of O-trityl anhydrothymidine with methyl triflate followed by reaction with NaBr or Nal gave the corresponding N(3)-methylated thymidines 65 (Nu = Br, I) in 70-90% yields <1993TL8411>. 

There was practically no reaction with sodium iodide, indicating that the tosyl group was not situated at position (5) and that the tosylation product was 3-tosyl-6-trityl-thymidine. Hence, the ether is 5-trityl-thymidine, and thymidine can be assigned a furanose ring. This conclusion received confirmation from their observation that, unlike guanosine and inosine, thymidine does not react with boric acid and therefore does not possess two adjacent cia hydroxyl groups. 

To initiate the first step of the repetitive synthesis, the trityl chloride derivative of polystyrene was subjected to reaction with thymidine in pyridine (Scheme 6). It is note-worthy that unreacted trityl chloride groups were blocked as methyl ethers by addition of methanol [41], The thymidine content was found to be 60-340 jumol g" after polymer-analogous cleavage from the support. This capacity corresponds to a degree of functionalization of 15-85% and points to steric problems of this attachment to the polymer. 

Replacement of the C-3 hydroxyl group of D-ribonucleosides (or ribonucleotides) with azido or amino groups forms 3 -azidothymidine (AZT) or 3 -amino-3 -deoxythymidine, both of which are used in the treatment of AIDS and cancer. These compounds are synthesized by the mesylation of l-(2 -deoxy-5 -0-trityl-p-D-lyxofuranosyl)-thymidine [100]. The mesyl group is displaced by reaction with lithium azide in DMF at 100°C. The azide can then be catalytically hydrogenated to give the 3 -amino analog (reaction 4.94). 

Hakimelahi has reported a novel strategy for the synthesis of N -purine acyclic nucleosides, in which the key step involves the reaction of [2-(p-methoxyphenyloxy)ethoxyl]methyl chloride and iV -tritylated nucleobases, followed by concomitant self-detritylation. 7-[(2-Hydroxyethoxy)methyl] guanine was phosphorylated by both HSV- and Vero-cell thymidine kinases to yield (92), and was found to have more potent cellular toxicity than acyclovir, while the adenine parent was phosphorylated by neither kinase. In addition, the N -adenine acyclic nucleoside phosphonate (93) was synthesised by alkylation of adenine with 3-bromopropionitrile to yield AT -(cyanoethyl)adenine, which upon... 

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