Novel isonucleoside analogues: synthesis of 2'-deoxy-2'-nucleobase-5'-deoxy-1',4'-anhydro-D-altritol

Article abstract of DOI:10.1016/S0957-4166(00)00136-1

A new class of isonucleoside analogues with branched-sugar 2'-deoxy-2'-nucleobase-5'-deoxy-1',4'-anhydro-D-altritol (21, 23a-c) has been synthesized from D-glucose in 11 steps. The construction of branched-chain sugars has been carried out by hydroboration-oxidation of a double bond in the corresponding hexose. The key intermediate 12 was synthesized from the branched-chain sugar 11 by the reductive cleavage reaction in the presence of TMSOTf and triethylsilane. A strong solvent effect was observed in the intramolecular nucleophilic substitution of 12. The protic solvent is favorable to form the bicyclic compound 18 by double S(N)2 substitution. The opening reaction of epoxide 17 by nucleobases was achieved regioselectively to give the desired isonucleosides in reasonable yield. Copyright (C) 2000 Elsevier Science Ltd.