New synthesis of (+/-)-isonucleosides

Structure: see text] A novel method for synthesizing isonucleosides, a new class of anti-HIV nucleosides, is described. 2,2-Dimethyl-1,3-dioxan-5-one was converted into a dioxabicyclohexane derivative in six steps. After cleaving the epoxide group with thiophenol, the resulting product was subjected to the Mitsunobu reaction in the presence of a nucleobase to give the desired isonucleoside derivative via migration of the thiophenyl group. Removal of the thiophenyl group under radical conditions followed by deprotection led to the 4'-substituted 2',3'-dideoxyisonucleosides as a racemic mixture.