Triester Approach Research Articles

Rapid access to synthetic lysobisphosphatidic acids using P(III) chemistry.

An expeditious route to synthetic lysobisphosphatidic acid S,S-1, its enantiomer, and regioisomers is reported. Synthetic difficulties concerning lipid stability and stereochemistry are bypassed using a phosphite triester approach in combination with multiple silyl protection. Spectroscopic studies evidence that acyl group migration in S,S-1 is accelerated by nonpolar solvents and inhibited by pyridine.

A New Approach to the Synthesis of Linear and Cyclic Oligoribonucleotides

The tetraribonucleoside triphosphate 15 and the cyclic tetraribonucleotide 16 have been prepared by a recently reported triester approach in solution, involving H-phosphonate coupling.

A comparison of histidine protecting groups in the synthesis of peptide-oligonucleotide conjugates

Abstract Protection of the imidazole ring of the histidine residue is not required for the elongation of an oligonucleotide chain at the side chain hydroxyl group of an amino acid residue by the phosphite triester approach. For the assembly of the peptide chain, the 2,4-dinitrophenyl group is the best alternative when histidine is placed at the C-terminal position.

Large scale synthesis of oligoribonucleotides on PEG by the phosphite triester approach

AbstractLarge scale synthesis of oligoribonucleotides has been successfully performed on PEG support by the phosphoramidite approach using t‐butyldimethylsilyl to protect the 2'‐hydroxyl group of ribonucleoside. By means of this procedure, the dodecamer r(AGUGGUCUUUGU) was synthesized in 98.1% average coupling yield, and 55 mg pure product was obtained from one gram of functionalized PEG.

Synthesis and biological activities of a phosphorodithioate analog of 2',5'-oligoadenylate.

To enhance the resistance of 2-5A (pppA2'p5'A2'p5'A) to degradation by exo- and endonucleases, a phosphorodithioate analog was synthesized using a solid-phase phosphite triester approach with N6-benzoyl-5'-O-dimethoxytrityl-3'-O-t-butyldimethylsilyladenosine 2'-[S-(beta-thiobenzoylethyl)-pyrrolidinophosphorothioamidit e]. 5'-Monophosphorylation was accomplished with 2-[2-(4,4'-dimethoxytrityloxy)-ethylsulfonyl]ethyl-(2-cyanoe thyl)-(N,N- diisopropyl)-phosphoramidite. The resulting product, p5'A2'(s2p)- 5'A2'(s2p)5'A, was approximately 10-fold less effective as an activator of purified human recombinant 2-5A-dependent RNase than was 2-5A itself. This loss of activation ability was related directly to the loss of binding ability of the phosphorodiothioate analog. As predicted, p5'A2'(s2p)5'A2' (s2p)5'A was stable to snake venom phosphodiesterase and the nucleolytic activities of both human lymphoblastoid CEM cell extracts and human serum, under conditions that led to facile degradation of parent 2-5A. This nuclease stability permitted the observation of the CEM cell extracts and human serum phosphatase activity which led to 5'-dephosphorylation of p5'A2'(s2p)5'A2'(s2p)5'A.

Stepwise solid-phase synthesis of nucleopeptide Phac-Ser(p 5′CATCAT)-Gly-Asp-OH from adenovirus-2 nucleoprotein

Nucleopeptide Phac-Ser(p 5′CATCAT)-Gly-Asp-OH, corresponding to the linking site of adenovirus-2 nucleoprotein, has been synthesised by a stepwise solid-phase methodology. After assembly of the peptide on a solid support, the oligonucleotide chain elongation was carried out at the hydroxyl group of the serine residue by the phosphite triester approach using 5′-phosphoramidite derivatives. The target nucleopeptide was then obtained in good yield after removal of the permanent protecting groups under mild basic conditions.

Criteria for the economic large scale solid-phase synthesis of oligonucleotides

The experimental conditions necessary for reducing the cost of large-scale solid-phase oligonucleotide synthesis by the phosphite triester approach have been studied using highly loaded polystyrene resins.

Solid-phase synthesis of the nucleopeptide fragment H-Asp-Ser[pAAAGTAAGCC]-Glu-OH from the nucleoprotein of Bacillus subtilis phage phi 29.

The naturally occurring DNA-nucleopeptide H-Asp-Ser[5'-pAAAGTAAGCC-3']-Glu-OH was prepared via a solid-phase phosphite triester approach using N-2-(tert-butyldiphenylsilyloxymethyl)benzoyl protected nucleosides. The oligonucleotide was linked via the extremely base-labile oxalyl ester anchor to the solid support.

Solid-phase synthesis of an RNA nucleopeptide fragment from the nucleoprotein of poliovirus.

The naturally occurring RNA-nucleopeptide H-Ala-Tyr[5'-pUUAAAAC-3']-NH2 is prepared via a solid-phase phosphite triester approach using N-SiOMB/O-TBDMS-protected nucleosides. Preliminary 1H-NMR studies show that the peptidyl unit has a remarkable effect on the conformational behaviour of the RNA moiety in the nucleopeptide.

An expedient synthesis of rac‐2,3‐di‐O‐stearoyl‐1‐thiophosphatidylcholine via thiophosphatidic acid diesters

AbstractA convenient triester approach to rac‐2,3‐di‐O‐stearoyl‐1‐thiophosphatidylcholine (7) involving the preparation of S‐[2,3‐bis(stearoyloxy)propyl] O‐(2,4‐dichlorophenyl) O‐methyl thiophosphate (4) followed by demethylation, coupling of the resulting salt 5 with choline 2‐mesitylenesulfonate and subsequent removal of 2,4‐dichlorophenyl protecting group is described.

Synthesis of a proposed isomer of F420having α-glutamyl bonding

A proposed isomer of redox coenzyme F420, having αglutamyl bonding, has been synthesized from 8-benzyloxy-10-D-ribityl-5-deazaflavin and α-L-glutamyl-L-glutamic acid moiety, by the phosphite triester approach followed by deprotection procedures.

Solid phase synthesis of a model nucleopeptide with a phosphodiester bond between the 5′ end of a trinucleotide and a serine residue

The model nucleopeptide Boc-Ser(pTCT)-NHcHex has been assmbled on a polystyrene solid support using the phosphite triester approach. Fmoc and cyanoethyl groups have been used to protect the exocyclic amine of cytosine and phosphate groups respectively. Final deprotection has been carried out by treatment with methanolic potassium carbonate.

Solid‐phase synthesis of RNA via a silyl‐protecting‐group strategy

AbstractRibonucleoside phosphoramidites have been prepared of which the exocyclic amino functions and 2′‐hydroxyl functions are protected with 2‐[(tert‐butyldiphenylsiloxy)methyl]benzoyl groups and tert‐butyldimethylsilyl groups, respectively. The N‐SiOMB/O‐TBDMS‐blocked nucleosides proved to be suitable building units in a solid‐phase synthesis of the RNA‐fragment 5′‐AGAGUACCU‐3′ via a phosphite triester approach.

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.

ChemInform Abstract: Regioselective Synthesis of Inositol Phosphate Diesters via a Cyclic Phosphate Triester Approach.

AbstractReaction of the 1,4,5,6‐tetra‐O‐benzyl‐myo‐inositol (I) with the benzyl phosphoramidite (II), followed by peracid oxidation and esterification with the alcohols (IV), yields a mixture of the phosphoric acid triesters (V) and (VI) with the former as the main products.

ChemInform Abstract: Application of the Phosphoramidite‐Phosphite Triester Approach for the Synthesis of Combinations Between Oxygenated Sterols and Nucleoside Analogues Linked by Phosphodiester Bonds.

AbstractThe recently developed phosphoramidite‐phosphite triester approach applied in solid phase DNA synthesis seems to be the technique of choice for the preparation of labile multifunctional compounds linked by phosphodiester bonds in solution.

Regioselective Synthesis of Inositol Phosphate Diesters via a Cyclic Phosphate Triester Approach

Regioselective Synthesis of Inositol Phosphate Diesters via a Cyclic Phosphate Triester Approach

Polysytyrene-supported synthesis by the phosphite triester approach: An alternative for the large scale synthesis of small oligodeoxyribonucleotides.

The large scale synthesis of two octadeoxyribonuclcotides has been successfully accomplished on polystyrene by the phosphite triester approach. Employing moderate excesses but high concentrations of phosphoramidites, the coupling yields are similar to those obtained in standard small scale syntheses.

Application of the phosphoramidite-phosphite triester approach for the synthesis of combinations between oxygenated sterols and nucleoside analogues linked by phosphodiester bonds

The recently developed phosphoramidite-phosphite triester approach applied in solid phase DNA synthesis seems to be the technique of choice for the preparation of labile multifunctional compounds linked by phosphodiester bonds in solution. Thus, to make the lipophilic oxysterols water-soluble for biological studies, we have prepared several combinations between polyoxygenated sterols and nucleoside analogues using Cβ-cyanoethoxy)bis(diisopropylamine) phosphine 2 as phosphorylating agent. This approach afforded the desired compounds of type 1 under very mild conditions and in reasonably high yields (> 60%).

Synthesis of phospholipids using an inverse phosphite triester approach

1,2-Diacylglycerols, prepared from allyl protected precursors, were transformed into glycerophosphatidylcholines through an acid catalysed coupling with a dialkyl phosphoramidite, followed by a one step deprotection–substitution reaction.