Thymidine phosphate

Scheme 6 illustrates the use of these protecting groups in the phosphorylation of 2 -deoxynucleosides by Michelson and Todd. 5 -0-Trityl-thymidine (110) was phosphorylated with dibenzyl phosphorochloridate (44) to (111), which, after treatment with 80% acetic acid, afforded thymidine 3-(benzyl phosphate) (112). Catalytic hydrogenolysis of (112) gave thymidine 3 -phosphate. Acetylation of (110) yielded the 3 -acetate (114) which, on detritylation to (115), followed by phosphorylation, catalytic reduction, and deacetylation, gave thymidine 5 -phosphate (116), identical with the thymidylic acid obtained by enzymic hydrolysis of 2 -deoxyribonueleic acid. A rather similar sequence was applied to the preparation of the 2 -deoxycytidine analogs of (113) and (116). 

Camerman showed that the N-T and N-3 atoms of the azido group of AZT 7e occupy positions near those of the two thymidine 3 -phosphate oxygen atoms [240]. Then, he hypothesized that if AZT is incorporated into viral DNA in place of thymidine, these N-T and N-3 azido nitrogens may form hydrogen bonds with enzyme atoms that normally bind to 0-3 of the polynucleotide and a phosphate oxygen atom of the next nucleotide to be added. 

The prerequisite thymidine 3 -phosphate may be synthesized from reaction of a phosphorochloridate (see above), or by the reaction with DCC. Even... 

W. Niewiarowski, W. J. Stec, and W. Zielinski (1980), Synthesis of 4-nitrophenyl esters of thymidine 3 -phosphate and 3 -phosphorothioate using a new phosphor-ylating agent. Chem. Comm. 524-525. 

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