State of the Art. Chemical Synthesis of Biophosphates and their Analogues via PIII Derivatives

Selective synthesis of chlorophosphoramidites using ionic liquids

“…Distilled from [C 4 dmim][NTf 2 ] at 88-90 • C at 0.01 mmHg, or extracted with diethyl ether to give a colourless liquid (46%). 1 ] (44%). Data from mixture of ionic liquid and product.…”

“…Nucleoside chemistry represents an important area of research for drug discovery, with oligonucleotide-based therapeutics being evaluated in preclinical and clinical studies for the treatment of a variety of disease states such as cancer, cardiovascular disease, diabetes and inflammatory disease disorders. [1][2][3] In order to prepare oligonucleotide-based therapeutics, nucleotides need to be synthesised by phosphorylation of partially protected nucleosides. Phosphorylation can be achieved in two ways; either by the introduction of a P V reagent or by phosphitylation with a P III reagent followed by oxidation.…”

Exploiting the use of ionic liquids to access phosphorodiamidites

“…To date, phosphorodiamidites, notably 2-cyanoethyl-N,N,N',N'-tetraisopropylphosphoramidite, have played a key role in solid phase oligonucleotide synthesis. 1 The use of these as synthetic precursors in oligonucleotide manufacture means that a number of nucleic acids are now at various stages of clinical trials for the treatment of a variety of disease states. 2 Beyond their use as synthetic precursors to oligonucleotides, phosphorodiamidites have been reported as starting materials for the synthesis of industrially relevant polymers as well as flame resistant materials such as adhesives, coatings and laminating materials.…”

Model synthesis of 2,3:5,6-di-O-isopropylidene- S-α-D-mannofuranosyl-N,N-diisopropylphosphoramidofluoridothioate and 2,3:5,6-di-O-isopropylidene-Se-α-D-mannofuranosyl-N,N-di-isopropylphosphoramidofluoridoselenoate via P(III)-OAr intermediates and a thiono-thiolo (selenono-selenolo) rearrangement

“…5 We have recently become interested in pursuing the use of specially designed phosphitylation reagents in the synthesis of glycosyl thiophosphates and their seleno-analogs as a possible alternative to the methods described above. We anticipated that such an approach could not only be more efficient but also would allow the construction of more complex glycosyl-phosphorus ester structures, such as those derived from thio-and seleno-fluorophosphoric acids.…”