An efficient method for the synthesis of 2 '-O-modified nucleosides via double alkylation using cyclic sulfates

The alkylation of N-3-benzyloxymethyl-5-methyluridine with 1,3,2-dioxathiol ane 2,2-dioxide or 1,3,2-dioxathiane 2,2-dioxide resulted in a 2'-O versus 3'-O selectivity of 3:1, respectively. The resulting product has a built-in sulfate leaving group at the terminal end of an ethyl or propyl carbon cha in, which can be displaced with sulfur and nitrogen nucleophiles to produce modifications at the 2'-O or 3'-O positions. (C) 2000 Elsevier Science Ltd . All rights reserved.