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

A new class of isonucleoside analogues with branched-sugar 2'-deoxy-2'-nucl eobase-5'-deoxy-1',4'-anhydro-D-altritol (21, 23a-c) has been synthesized f rom D-glucose in Il steps. The construction of branched-chain sugars has be en carried out by hydroboration-oxidation of a double bond in the correspon ding hexose. The key intermediate 12 was synthesized from the branched-chai n 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 t he bicyclic compound 18 by double S(N)2 substitution. The opening reaction of epoxide 17 by nucleobases was achieved regioselectively to give the desi red isonucleosides in reasonable yield. (C) 2000 Elsevier Science Ltd. All rights reserved.