SYNTHESIS OF 3'-C-BRANCHED 1',5'-ANHYDROMANNITOL NUCLEOSIDES AS NEW ANTIHERPES AGENTS

A series of 3'-beta-C-branched anhydromannitol nucleosides were conven iently synthesized starting from commercially available D-ribose. The reaction sequences were: (i) conversion of the protected pentofuranose to the corresponding nitrohexopyranose; (ii) addition of the conjugat ed base of the nitrosugar to formaldehyde; (iii) removal of the nitro group by n-tributyltin hydride treatment and (iv) Mitsunobu type alkyl ation to introduce the nucleobase. The conformation of intermediates a nd final compounds were deduced from NMR analysis. The thymine congene r showed potent activity against herpes simplex virus (HSV). (C) 1998 Elsevier Science Ltd. All rights reserved.