A series of 3'-beta-C-branched anhydromannitol nucleosides were conveniently 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 conjugated base of the nitrosugar to formaldehyde; (iii) removal of the nitro group by n-tributyltin hydride treatment and (iv) Mitsunobu type alkylation to introduce the nucleobase. The conformation of intermediates and final compounds were deduced from NMR analysis. The thymine congener showed potent activity against herpes simplex virus (HSV). (C) 1998 Elsevier Science Ltd. All rights reserved.