New chiral acyclic analogs of 2′-deoxynucleosides

Abstract

Convenient methods for the synthesis of chiral 2′,3′-seco-2′-deoxynucleosides were developed. An isopropylidene protective group was used to block the 3′,5′-hydroxy groups in 2′,3′-seco-uridine. Conversion of the hydroxymethyl group to a methyl group was accomplished by chlorination with a mixture of CCl₄ and Ph₃P with subsequent reduction with n-Bu₃SnH. 2′,3′-seco-2′-Deoxyuridine was obtained after deacetonation. The (S) enantiomer was similarly synthesized starting from 1-(α-D-arabinofuranosyl)uracil. 3′-O-tert-Butyldimethylsilyl-5′-O-(p-monomethoxytrityl)-2′,3′-seco-2′-deoxyuridine, which has optically active centers at C_(1′) and C_(4′), was also synthesized.