Synthesis of novel nucleosides with a fused cyclopropane ring substituted by a hydroxymethyl group

The two diastereomers of a 3-oxabicyclo[3.1.0]hexan-2-ol 21a-b with the cyc lopropane ring substituted by a hydroxymethyl group were synthesized from b oth products 17a and 18a obtained from the bromohydroxylation of epoxide 16 a derived from 3-oxabicyclo[3.2.0]hept-6-en-2-one 15. This preparation invo lved two stereospecific C-4-C-3 ring contractions leading to cis,cis-trisub stituted cyclopropane compounds 18a and 12. The hydroxylactols 21a-b thus o btained were diacetylated and the single product 22 was subjected to substi tution at the anomeric position by protected or free bases, providing, in e ach case, only one of the possible products. Deprotection with ammonia yiel ded new bicyclic nucleosides 11a-d. (C) 2000 Elsevier Science Ltd. All righ ts reserved.