Adenosine 5 -phosphoramidates, preparation

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." ... 

With familiarity of the various protecting groups available for the hydroxyl and base amino functions, it is possible to prepare nucleoside intermediates with reactive groups available only for the formation of a 3, 5 -phospho-diester linkage. Unwanted reactions (3, 3 - or 5, 5 -phosphodiester formation, phosphoramidate formation, etc.) cannot possibly occur with the selection of appropriate intermediates. A representative example would be the condensation between adenosine and uridine ... 

In the area of cyclic phosphates, adenosine 3, 5 -cyclic phosphorofluoridate has been prepared it was shown to undergo facile conversion to adenosine 2, 3 -cyclic phosphate. A photolabile 3, 5 -cyclic phosphotriester of adenosine has been described,as have 3, 5 -cyclic phosphotriesters and phosphoramidates of 8-chloroadenosine. ... 

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