Synthesis of 4-substituted carbocyclic 2,3-dideoxy-3-C-hydroxymethyl nucleoside analogues as potential anti-viral agents

The synthesis of two carbocyclic guanosine analogues with an electronegativ e fluoro or hydroxy substituent in the 4-position is described. The cyclope ntanols 17a and 18 were synthesized from enantiomerically pure 3S,4S-bis(hy droxymethyl)cyclopentanone ethylene glycol ketal (7) via a number of key st eps involving stereospecific reduction of the keto function and a dihydroxy lation of the C-4 methylene. Substitution of the tertiary C-4 hydroxyl grou p in 16 with fluorine using bis-(2-methoxyethyl)aminosulfur trifluoride (De oxo-Fluor(TM)) and coupling of the cyclopentanol-moiety with 2-amino-6-chlo ropurine using the Mitsunobu procedure gave compounds 3 and 4 which have be en evaluated as potential anti-viral agents. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.