1‐(2′‐Deoxy‐β‐D‐xylofuranosyl)cytosine: Base pairing of oligonucleotides with a configurationally altered sugar‐phosphate backbone

Solid‐phase synthesis of the oligo(2′‐deoxynucleotides) 19 and 20 containing 2′‐deoxy‐β‐ D ‐xylocytidine ( 4 ) is described. For this purpose, 1‐(2‐deoxy‐β‐ D ‐ threo ‐pentofuranosyl)cytosine ( = 1‐(2‐deoxy‐β‐ D ‐xylofuranosyl)‐cytosine; 4 ) was protected at its 4‐NH 2 group with a benzoyl (→ 5 ) or an isobutyryl (→ 8 ) residue, and a dimethoxytrityl group was introduced at 5′‐OH (→ 7, 10 ; Scheme 2 ). Compounds 7 and 10 were converted into the 3′‐phosphonates 11a,b . While 19 could be hybridized with 21 and 22 under formation of duplexes with a two‐nucleotide overhang on both termini ( 19 · 21 : T m 29°; 19 · 22 : T m 22°), the decamer 20 bearing four xC d residues could no longer be hybridized with one of the opposite strands. Moreover, the oligonucleotides d[(xC) 8 C] ( 13 ), d[(xC) 4 C] ( 14 ), d[C(xC) 4 C] ( 15 ), and d[C(xC) 3 C] ( 16 ) were synthesized. While 13 exhibits an almost inverted CD spectrum compared to d(C 9 ) ( 17 ), the other oligonucleotides show CD spectra typical for regular right‐handed single helices. At pH 5, d[(xC) 8 C] forms a stable hemi‐protonated duplex which exhibits a T m of 60° (d[(CH + ) 9 ] · d(C 9 ): T m 36°). The thermodynamic parameters of duplex formation of ( 13H + · 13 ) and ( 17H + · 17 ) were calculated from their melting profiles and were found to be identical in Δ H but differ in Δ S ( 13H + · 13 : Δ S = −287 cal/K mol; 17H + · 17 : Δ S = −172 cal/K mol).