A new entry to nucleoside phosphorofluoridate and nucleoside phosphorofluoridothioate diesters

A new method for the formation of the P–F bond

“…Compounds 5a and 5b prepared in this study were identical (TLC, 1 H and 31 P NMR and FABMS) those synthesised via the iodine-promoted oxidation of the corresponding dinucleoside H-phosphonate and H-phosphonothioate in the presence of TAF. 2 The relevance of the procedure to the preparation of oligonucleotide analogues was assessed by carrying out some preliminary 31 P NMR experiments on unprotected dinucleoside phosphorothioates. To this end, dithymidine phosphorothioate (obtained by the detritylation of 4a, followed by trituration with diethyl ether) was subjected to the reaction with iodine (5 equiv.)…”

Phosphorofluoridic acid ammonium salts and acids: Synthesis, NMR properties, and application as acid catalysts

“…Additionally, a 19 F nucleus can be a probe for disclosing some interaction between phosphoric acid derivatives and biologically relevant molecules. Metal fluorides such as KF [4,5] and AgF [6,7], hydrogen fluoride/amine complexes [8,9], and diethylaminosulfur trifluoride (DAST) [10] are used as fluorinating agents for phosphorus chlorides and esters. Tetrabutylammonium fluoride (TBAF) has also been used to introduce fluorine atom to the phosphorus atom [5].…”

Silylation‐Mediated Transesterification of O‐Phenyl H‐Phosphonothioates − A New Entry to Nucleoside H‐Phosphonothioate Monoesters

“…Due to their higher stability, ease of handling, and efficiency in solid-phase synthesis, [6Ϫ8] H-phosphonothioate building blocks [1,9] seem to be superior to phosphorothioamidite derivatives [10] in the synthesis of nucleotide analogues with multiple modifications at the phosphorus centre that are difficult to prepare in other ways, for example from nucleoside phosphorodithioates, [6,7,11,12] nucleoside phosphoramidothioates, [13] nucleoside phosphorofluoridothioates, [14] etc. Despite their usefulness in the synthesis of various types of phosphorus compounds, there are only a handful of synthetic methods available for the preparation of nucleoside H-phosphonothioate monoesters.…”

“…During the last decade we have introduced and have been investigating various aspects of H-phosphonothioates (''H'' indicates a PϪH bond) [1Ϫ5] as a new type of synthetic intermediates for the preparation of biologically active phosphorus compounds based on H-phosphonate methodology. Due to their higher stability, ease of handling, and efficiency in solid-phase synthesis, [6Ϫ8] H-phosphonothioate building blocks [1,9] seem to be superior to phosphorothioamidite derivatives [10] in the synthesis of nucleotide analogues with multiple modifications at the phosphorus centre that are difficult to prepare in other ways, for example from nucleoside phosphorodithioates, [6,7,11,12] nucleoside phosphoramidothioates, [13] nucleoside phosphorofluoridothioates, [14] etc.…”