Innovative Cyclic Nucleotides – Nucleoside 2′,3′‐Seven‐Membered Cyclic Diphosphonate Derivatives. Theoretical Feasibility, Synthesis, and Properties
Year: 2025
Type: article
Abstract: 7‐membered cyclic nucleotides have remained unknown despite the natural abundance of their 5‐ and 6‐membered counterparts. Here, we report the first synthesis of 2′,3′‐cyclic nucleosides (tetrathio)diphosphonate (2′,3′‐cNTDPs) by a rapid one‐step, regioselective, and protection‐free reaction of U, A, C, I, and G, with methylene‐bis(1,3,2‐dithia‐phospholane‐2‐sulfide) (DTPS). The reaction proceeds instantaneously, even at ‐35 °C, resulting in the quantitative conversion of methylene‐bis‐DTPS. Density functional theory (DFT) calculations of ∆G r confirm the synthetic feasibility and regioselectivity, attributing the efficiency to strain release in DTPS rings and entropic gain from thiirane elimination. The resulting 2′,3′‐cNTDPs exhibited remarkable hydrolytic stability and greater solution structural rigidity than free nucleosides.
Source: Chemistry - A European Journal
Authors: Sveta Liberman, Lea Bobot, Hadar T Ben Daniel, Dan T Major, Bilha Fischer
Institution: Bar-Ilan University
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: hybrid
Estimated APC paid: $4,640
OpenAlex ID: W4410723335