Constrained Nucleic Acids (CNA). Part 2. Synthesis of Conformationally Restricted Dinucleotide Units Featuring Noncanonical α/β/γ or δ/ε/ζ Torsion Angle Combinations

Four dinucleotide building units of nucleic acids in which three out of six backbone torsion angles are included in a dioxaphosphorinane ring structure (D-CNA family) have been synthesized: two diastereoisomeric α,β,γ-D-CNA {cis and trans} and two diastereoisomeric δ,ε,ζ-D-CNA {(S C4 ‘,R P) and (S C4 ‘,S P)}. The structural analysis of these conformationally restricted dinucleotides, using NMR spectroscopy and X-ray crystallography, shows that these D-CNA structural elements allow the stabilization of torsion angle combinations, α/β/γ and δ/ε/ζ, that are significantly different from those typically observed in canonical A- or B-form duplexes.