Thymidine displacement reaction

Synthesis of the thymidine derivative relies on the older two-step insertion of fluorine. Thus, the hydroxyl group in 3 -deoxythymidine benzoate (51-1) is first converted to the mesylate (51-2). Reaction with potassium fluoride in hydrogen fluoride replaces the mesylate by fluorine (51-3). The fact that this reaction, as that above, proceeds with retention of the configuration mles out simple displacement as the mechanism for this transform. The presence of the methyl group at position 5 negates the need for the chlorination step. Saponification then affords the antiviral agent alovudine (51-4) [52]. 

The first example of a pyrimidine anhydronucleoside containing an imino bridge was prepared by treatment of 2,5 -anhydro-3 -0-(methylsulfonyl)thymidine (152) with liquid ammonia at room temperature.422 Under these reaction conditions, displacement of the 3 -methylsulfonyloxy group of the presumed isocytidine intermediate... 

The oxorhenium(V) complex 80 has been prepared from 2, 3 -diamino-2, 3 -dideoxyadenosine, and exists as a 2 1 mixture of syn- and an/i-isomers. Both were inhibitors of purine-specific ribonuclease, with the 57/i-isomer being more effective. " The same group has described a route to 3, 5 -diamino-3, 5 -dideoxy-adenosine (82) from the /> xo-epoxide 81 (Vol. 25, p. 251-2), as outlined in Scheme 10. The Mitsunobu inversion using benzyl alcohol as nucleophile is noteworthy, and proved superior to other strategies. An oxorhenium(V) complex was also formed from 82." Thymidine can be converted into the anhydronucleo-side 83 by two successive Mitsunobu reactions, and 83 was converted into the aminoderivative 84 of AZT, and some phosphoramidates were produced from 84." Some 5 -deoxy-5 -sulfonylamido derivatives of AZT have also been produced by successive displacements at 0-5 and 0-3 by nitrogen nucleophiles." ... 

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). 

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