Diastereoselective Synthesis of a Conformationally Restricted Dinucleotide with Predefined α and β Torsional Angles for the Construction of α,β-Constrained Nucleic Acids (α,β-CNA)

The synthesis of a diastereopure 1,3,2-dioxaphosphorinane linkage in which two, α and β, out of six torsion angles of the natural phosphodiester backbone are constrained with predefined values of ca. +60° (g+) and 180° (t), respectively, is described. The stable and unstrained six-membered cyclic phosphotriester structure represents the smallest possible ring allowing the conformational locking of the α torsion angle at a significant positive value that is typical of many bulged regions of nucleic acids.