4‑Toluenesulfonyloxymethyl‑(<i>H</i>)‑phosphinate: A Reagent for the Introduction of <i>O</i>- and <i>S</i>‑Methyl‑(<i>H</i>)‑phosphinate Moieties

The straightforward synthesis of sodium 4-toluene­sulfonyl­oxymethyl-(<i>H</i>)-phosphinate and (<i>H</i>)-phosphino­methyl­isothio­uronium tosylate as new reagents for the preparation of <i>O</i>- and <i>S</i>-methyl-(<i>H</i>)-phosphinic acid derivatives, respectively, is described. The reactivity of both reagents was demonstrated by the preparation of protected 2′-deoxy­ribonucleo­side-<i>O</i>-methyl-(<i>H</i>)-phosphinates in the 5′- and 3′-series and 2′,5′-dideoxy­ribonucleo­side-5′-<i>S</i>-methyl-(<i>H</i>)-phosphinates. These compounds represent a new class of monomers compatible with the solid phase synthesis of oligonucleotides by <i>H</i>-phosphonate chemistry, as it was proved with the synthesis of a fully phosphonate heptamer

Straightforward Synthesis of Purine 4′-Alkoxy-2′-deoxynucleosides: First Report of Mixed Purine–Pyrimidine 4′-Alkoxyoligodeoxynucleotides as New RNA Mimics

Purine and pyrimidine 4′-alkoxy-2′-deoxynucleosides were efficiently prepared from nucleoside 4′-5′-enol acetates in three steps by <i>N</i>-iodosuccinimide promoted alkoxylation, hydrolysis, and reduction followed by conversion to phosphoramidite monomers for the solid-phase synthesis of the oligonucleotides. Fully modified 4′-alkoxyoligodeoxynucleotides, which are characterized by a prevalent <i>N</i>-type (RNA-like) conformation, exhibited superior chemical and nuclease resistance as well as excellent hybridization properties with a strong tendency for RNA-selective hybridization, suggesting a potential application of 4′-alkoxy-oligodeoxynucleotides in antisense technologies