Wojciech Dabkowski

Synthesis of 2′-deoxynucleosid-3′-yl-N,N-diisopropylaminophosphorfluoridites. A new class of stable PIII nucleotides containing a PF bond

Abstract A new methodology based on phosphitylating reagents containing 4-nitrophenoxy leaving group has been employed to synthesize stable 5′-O-(4,4-dimethoxytrityl)nucleosid-3′-yl-N,N-diisopropylaminophosphorfluoridites 1a-d .

Studies on the Efficient Generation of PhosphorusCarbon Bonds via a Rearrangement of PIII Esters Catalysed by Trimethylhalosilanes

Halotrimethylsilanes Me(3)SiX (X = Br, I) catalyse rearrangements of tricoordinate phosphorus esters RRP-OR into the corresponding phosphoryl systems RRP(O)R. This provides a simple and efficient route to a variety of structures containing phosphorus-carbon bonds, under mild conditions and with good yields. The reaction mechanism was investigated in detail by (31)P NMR spectroscopy and independent synthesis of the reaction intermediates. It has been demonstrated that the primary products of this catalytic reaction are halogeno P(III) structures RRPX and silyl ethers ROSiMe(3) and that they subsequently react to give the corresponding phosphorus silyl esters-Me(3)SiOPRR-and alkyl halides RX. At higher temperatures these intermediates then react to form RRP(O)R compounds. This paper also features the surprising observation that when esters Ph(2)POR and halotrimethylsilanes Me(3)SiX (X = Br, I) are used in 2:1 ratio, phosphonium salts Ph(2)R(2)P(+)X(-) and trimethylsilyl diphenylphosphinate--Ph(2)P(O)OSiMe(3)--are formed as the major products. Experimental evidence indicates that the mechanisms of both reactions are fundamentally different from that of the Michaelis-Arbuzov reaction. Me(3)SiCl is not reactive and this paper explains why.

N, N-Diisopropyl-O-Methyl-O-4-Nitrophenyl Phosphoramidite. New Flexible Phosphitylating Reagent in the Synthesis of Thio- and Seleno- Oligonucleotides

Abstract Internucleoside coupling by the title reagent, illustrated by synthesis of dinucleoside and trinucleoside thiophosphates and selenophosphates is accomplished by a new strategy involving the displacement of 4-nitrophenoxy group. Sodium 4-nitrophenolate formed in situ facilitates the oxidation of the intermediate pIII structures and acts as a demethylating reagent.

A viologen phosphorus dendritic molecule as a carrier of ATP and Mant-ATP: spectrofluorimetric and NMR studies

In this work, the interactions between a viologen phosphorus dendrimer of generation 0 (VPD) and ATP or 2′-/3′-O-(N′-methylanthraniloyl)-ATP (Mant-ATP) were investigated by NMR and fluorescence spectroscopy methods. ATP and Mant-ATP were used as model molecules of purine and pyrimidine nucleoside analogues (NAs), which are antimetabolites commonly used in anticancer therapy. Complexes of VPD with NAs may help to overcome severe limitations of NAs associated with their low solubility, stability or resistance to cancer cells. The aim of the presented study was to evaluate the stoichiometry and the mechanism of formation of complexes between dendrimers and nucleotides: ATP and Mant-ATP. Moreover, we examined the efficiency of complex formation in relation to temperature, the type of solvent, NaCl concentration, pH and environment polarity. It was observed that viologen phosphorus dendrimers form complexes with ATP and Mant-ATP with high efficiency. Obtained complexes are stabilized by electrostatic and aromatic–aromatic interactions as driving forces.

Highly selective O-phosphitylation of amino alcohols using PIIIreagents containing 4-nitro and 2,4-dinitro aryloxy leaving groups

A method for direct highly O-selective phosphitylation of amino alcohols by reagents containing a 4-nitrophenoxy or 2,4 dinitrophenoxy leaving group has been developed. This method provides mild reaction conditions to access O-phosphitylated amino alcohols. The flexibility of the synthesis is exemplified by the models of simple amino alcohols and of nucleosides containing unprotected NH2 groups.

Stereoselective Synthesis of Nucleoside Phosphorofluoridates

Abstract The reaction of diastereoizomeric 3′-[5′-O-(monomethoxytrityl)thymidyl]-5′-(3′-O-monomethoxytrityl)thymidine O-methyl phosphoro-thioate and 3′-[5′-O-(monomethoxytrity1) thymidy1]-5′-(3′-O-monomethoxytrityll-N6 -benzoyladenosine O-methyl phosphorothioate with sulfuryl-chloride fluoride leads to the corresponding diastereoisomeric phosphorofluoridates in highly stereoselective manner.

Phosphino sulphonates, a type of PIII-anhydride and their isomerisation into phosphinoyl sulphinates: a novel rearrangement in phosphorus–sulphur chemistry

The imidazolides (1) react smoothly with RSO3H to afford a novel class of trico-ordinate phosphorus anhydride, the phosphino sulphonates (2); under sutable structure circumstances the compounds (2) undergo a novel type of rearrangement, (2)→(6), which provides the first example of a phosphinoyl sulphinate structure (6).

TRIMETHYLCHLOROSILANE: A NOVEL ACTIVATING REAGENT IN NUCLEOTIDE SYNTHESIS VIA THE PHOSPHORAMIDITE ROUTE

Trimethylchlorosilane (TMSCl) is a remarkably efficient activator in nthe reaction of phosphorus(III) amides with nucleosides to give nphosphorus(III) esters in excellent yield.

Novel routes to tri- and tetracoordinate phosphorus-fluorine compounds directed to synthesis of P-F modified nucleotides

Abstract Fluoroderivatives of phosphorus are important in the chemistry and biochemistry of both elements.1. Recently, our attention has been Focused on the synthesis of non-ionic oligodeoxynucleoside-phosphoro fluoridates and their thio− and selenoanalogues. Existing methods were, in our opinion, not suited for the synthesis of oligonucleoside− phosphorofluorides. So we devised new ones.

Silyloxyphosphanes. New Phosphitylating Reagents in Nucleotide Chemistry

Abstract Letsinger et al. developed a phosphite method of synthesis of oligonucleotides. This method was further improved by Carruthers et al. Our present work is a useful extension of the Letsinger-Carruthers type reagents. Recently, we have been able to demonstrate that bis- (N, N-diisopropylamino)trimethylsilyloxy phosphane exhibit phosphitylating properties in the presence 1-H-tetrazole.1 Preparation of this reagent and its ability to undergo selective nucleophilic substitution at the tricoordinate phosphorus atom without affecting the silicon center under conditions which are commonly used for the phosphite triester approach has been recently described.1 In the same paper we reported remarkable chemical properties of dinucleosidetrimethyl-siloxyphosphanes. Namely their participation in Michaelis-Arbuzov type reactions under extremely mild conditions and reactions with oxalylazolides and sulfuryl chloride fluoride which are unique for these reagents.