An Improved P(V) Thio-Oligonucleotide Synthesis Platform.

Three critical advances in simplifying the adoption of P(V)-based stereopure, phosphorothioate-containing oligonucleotide synthesis are reported. A more inexpensive phosphorus-sulfur incorporation reagent () is introduced, a robust linker system was developed, and a systematic study of common nucleobase protecting groups was performed to significantly reduce the barrier to adoption of this technology.

Nature Chose Phosphates and Chemists Should Too: How Emerging P(V) Methods Can Augment Existing Strategies.

Phosphate linkages govern life as we know it. Their unique properties provide the foundation for many natural systems from cell biology and biosynthesis to the backbone of nucleic acids. Phosphates are ideal natural moieties; existing as ionized species in a stable P(V)-oxidation state, they are endowed with high stability but exhibit enzymatically unlockable potential.

A P(V) platform for oligonucleotide synthesis.

The promise of gene-based therapies is being realized at an accelerated pace, with more than 155 active clinical trials and multiple U.S. Food and Drug Administration approvals for therapeutic oligonucleotides, by far most of which contain modified phosphate linkages.

Mild and Chemoselective Phosphorylation of Alcohols Using a Ψ-Reagent.

An operationally simple, scalable, and chemoselective method for the direct phosphorylation of alcohols using a P(V)-approach based on the Ψ-reagent platform is disclosed. The method features a broad substrate scope of utility in both simple and complex settings and provides access to valuable phosphorylated alcohols that would be otherwise difficult to obtain.