Preparation of 2,2 '-anhydronucleosides: regio- and stereoselective modifications of the base and sugar moieties

2'-Deoxy-2'-iodonucleosides 4-9, obtained from suitably protected furanoid glycals 1 and 2 with different silylated pyrimidine bases, were transformed into the corresponding 2,2'-anhydronucleosides 10-15 with inversion of the configuration at C-2', by heating in DMF with n-dibutyltin oxide. Regio- a nd stereospecific opening at C-2' of the 2,2'-ring in compounds 10, 11, and 12 with sodium azide afforded the related 2'-azido-2'-deoxynucleosides 16, 17 and 18, respectively. Action of sodium hydroxide on 12 caused the regio selective opening of the above-mentioned ring at C-2 with retention of the configuration at C-2' giving 19. Compound 19 could be transformed straightf orwardly into 18 by well-established methodology. On the other hand, compou nd 15 could be transformed into the related 2',3'-anhydronucleoside 23 by a regio- and stereoselective addition at N-3-C-2' of allyl bromide concomita nt with 2,2'-ring opening and inversion of the configuration at C-2' to aff ord the intermediate 2'-bromo-2'-deoxynucleoside 21, which was subsequently treated with sodium methoxide giving 23. (C) 2000 Elsevier Science Ltd. Al l rights reserved.