Wojciech Dąbkowski

2,4-Dinitrophenol: a novel activating reagent in nucleotide synthesis via the phosphoramidite route. Design of new effective phosphitylating reagents☆

Abstract 2,4-Dinitrophenol (DNP) is a remarkably efficient activator in the reaction of P(III) amides with nucleosides to give P(III) esters in excellent yield. Typical examples of this novel procedure are presented herein. Mechanistic features of the activation were elucidated by model studies of the reaction of bis(2-cyanoethyl)diisopropylphosphoroamidite with benzyl alcohol. The importance of the initial protonation stage and formation of an intermediate P(III)-2,4-dinitrophenyl ester were clearly demonstrated by 31 P NMR spectroscopy and independent synthesis. New phosphitylating reagents containing the 2,4-dinitrophenoxy group do not require any activation.

Fluorination of trimethylsilyl phosphites and their structural analogues by sulfuryl chloride fluoride: simple preparation of phosphorofluoridates and related compounds, including deoxynucleoside phosphorofluoridates

Trimethylsilyl esters of general formula RR′POSiMe3 react in a quantitative and fully chemoselective way with sulfuryl chloride fluoride, ClSO2F, under extremely mild conditions to give phosphorofluoridates RO(R′O)P(O)F of high purity. This work provides easy access to all type of fluoridates from non-toxic starting materials. The synthetic usefulness of this method is illustrated by the synthesis of 3′- and 5′-mononucleoside phosphorofluoridates 10 and 3′,5′-dinucleoside phosphorofluoridates 11 from the corresponding nucleoside trimethylsilyl phosphites.

New general synthesis of organophosphorus P–F compounds via reaction of azolides of phosphorus acids with acyl fluorides: novel route to 2-deoxynucleosidyl phosphorofluoridates and phosphorodifluoridates

Tetra- and tri-coordinate P–N-imidazole derivatives and their structural analogues react smoothly with acyl fluorides to give the corresponding P–F compounds in almost quantitative yield. This method has been successfully applied to produce 2-deoxynucleosidyl phosphorofluoridates and phosphorodifluoridates.

Diastereoisomerically pure dinucleosidylphosphorofluoridites and their application in stereospecific synthesis of dinucleosidylphosphorofluoridothionates

Dinucleosidylphosphorofluoridites with dA(Bz), dC(Bz) or dT at the 3′-end and dT at the 5′-end are synthesised, separated into their diastereoisomers and shown to be converted stereospecifically into the corresponding phosphorofluoridothionates high hydrolytic stability.

New Efficient Synthesis of Thymidine Cyclic 3′, 5′- Phosphorofluoridate and Its Sulfur Analogue via the Phosphoroamidite Route

Abstract We describe the convenient synthesis of thymidine cyclic 3′, 5′-phosphorofluoridate 6, which is superior to that previously reported. Our procedure is based on a sequence of reactions utilizing 3 as the key substrate. Similar sequence of reaction leads to the sulfur analogues of 6 the thymidine cyclic 3′, 5′-phosphorofluoridothioate 7.

New efficient synthesis of phosphonofluorodithioates ROP(S)(S–)F and their structural analogues

The title compounds 3 are formed in very high yield from a one-pot sequential reaction of 1,3,2-dithiaphospholane PIII derivatives 1, which are transformed into the corresponding PIV compounds 2 by addition of elemental sulfur and finally into fluoridodithioates 3 by TBAF.

Novel phosphitylating reagents containing a phosphorus–fluorine bond and their application in efficient synthesis of phosphorofluoridates and phosphorofluoridothionates

Novel phosphitylating reagents containing a P–F bond are obtained in excellent yield from commercial materials. They react with alcohols at 20 °C in neutral solvents in the presence of tetrazole, chlorotrimethylsilane or benzoyl chloride to give the intermediate phosphorofluoridites. Subsequent oxidation or sulfurization followed by the removal of protecting groups gives the phosphorofluoridates and thiophosphorofluoridates in over 90% total yield.

New Strategies for Chemical Synthesis of Phosphorodithioates Derived from 2′- or 3′- or 5′-Thionucleosides

Abstract Various phophorodithioates derived from thionucleosides were synthesis by the reaction anhydronucleosides with phosphorodithioic acids

New phosphitylating reagents containing aryloxy leaving group. Applications in nucleotide chemistry

Abstract Synthetic oligonucleotides bearing modifications in the backbone have potentials as tools in studying and controlling biological processes.

The phosphorofluoroamidite approach to mixed phosphites

Abstract A new convenient and general procedure is described for the preparation of mixed phosphites from readily available phosphorofluoroamidites by stepwise replacement of amino and fluoro-groups in the presence of trimethylchlorosilane (Me 3 SiCl). The reaction mechanism is briefly discussed.