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

Lipophosphonoxins II: Design, Synthesis, and Properties of Novel Broad Spectrum Antibacterial Agents

The increase in the number of bacterial strains resistant to known antibiotics is alarming. In this study we report the synthesis of novel compounds termed Lipophosphonoxins II (LPPO II). We show that LPPO II display excellent activities against Gram-positive and -negative bacteria, including pathogens and multiresistant strains. We describe their mechanism of action–plasmatic membrane pore-forming activity selective for bacteria. Importantly, LPPO II neither damage nor cross the eukaryotic plasmatic membrane at their bactericidal concentrations. Further, we demonstrate LPPO II have low propensity for resistance development, likely due to their rapid membrane-targeting mode of action. Finally, we reveal that LPPO II are not toxic to either eukaryotic cells or model animals when administered orally or topically. Collectively, these results suggest that LPPO II are highly promising compounds for development into pharmaceuticals