Synthesis of tritium- and deuterium-labeled 9-.beta.-D-arabinofuranosyladenine and the tritium-labeled 5'-monophosphate ester with increased metabolic stability

Abstract

Preparation of both a 5'-deuterium and a 5'-tritium-labeled 9-beta-D-arabinofuranosyladenine (6a and 6b) by reduction of the protected 5'-aldehyde 4 is described. Conversion of 6b to the 5'-tritium-labeled 5'-monophosphate 7b was effected directly with a phosphoryl chloride-formic acid reagent. The product 7b exhibited consistently higher blood levels of nonvolatile tritium than the 2-labeled compound when tested in dogs.

Synthesis of tritium-labelled biologically important diazines

“…The general method used for the synthesis of nucleosides labelled with tritium at the 5 H -atom of the carbohydrate residue is based on the reduction of b-D-ribopentodialdo-1,4-furanosides of respective nucleic bases with gaseous tritium or sodium boro[ 3 H]hydride. This method was used for the preparation of compounds labelled at the 5 H -position, such as 9-b-arabinofuranosyladenine, 141 thymidine, 138 2 H ,3 H -O-isopropylideneadenosine. 142 In order to prepare adenosine, guanosine and uridine labelled with tritium at C(5 H ), Akulov et al 143 conducted the reduction reaction using gaseous tritium in the presence of a catalyst as well as sodium boro[ 3 H]hydride.…”