- ON-DEMAND PHOSPHORAMIDITE SYNTHESIS
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The invention relates to a method of synthesis of phosphoramidites by immobilization of a phosphitylation agent on a resin activated to create a charged resin, then putting in contact with the charged resin with a suitable substrate. Phosphoramidites are synthesized in a few minutes from the application of the starting materials. Thus, the process makes it possible to create specific phosphoramidites on demand when they are needed in other applications. The substrates to be applied are mainly nucleosides, thus making it possible to create nucleoside phosphoramidites for the subsequent synthesis of oligonucleotides.
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Page/Page column 36-38; 48
(2022/01/24)
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- BICYCLIC PEPTIDE LIGAND STING CONJUGATES AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00549
(2020/08/28)
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- Microwave-assisted preparation of nucleoside-phosphoramidites
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Microwave-assisted phosphitylation of sterically hindered nucleosides is demonstrated to be an efficient method for the preparation of corresponding phosphoramidites (otherwise onerous under standard conditions) and is shown to be general in its applicability. the Partner Organisations 2014.
- Meher,Efthymiou,Stoop,Krishnamurthy
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supporting information
p. 7463 - 7465
(2014/07/07)
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- Overcoming hydrolytic sensitivity and low solubility of phosphitylation reagents by combining ionic liquids with mechanochemistry
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Ionic liquids have been used in combination with ball milling on a range of chlorophosphoramidite reagents to phosphitylate nucleosides and 2-deoxynucleosides. The enhanced stability offered by the ionic liquid mediated processes combined with efficient mass transfer induced by ball milling has enabled excellent yields to be obtained even when using small dialkyl amino groups as well as the more commonly used diisopropylamino protection.
- Hardacre, Christopher,Huang, Haifeng,James, Stuart L.,Migaud, Marie E.,Norman, Sarah E.,Pitner, William R.
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supporting information; experimental part
p. 5846 - 5848
(2011/06/26)
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- Selective synthesis of chlorophosphoramidites using ionic liquids
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A range of chlorophosphoramidites have been prepared in ionic liquids and compared with material synthesised in molecular solvents. Through the use of ionic liquids as reaction media the moisture sensitivity and impurity issues hampering existing traditio
- Amigues, Eric J.,Hardacre, Christopher,Keane, Gillian,Migaud, Marie E.,Norman, Sarah E.,Pitner, William R.
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experimental part
p. 1391 - 1396
(2010/05/18)
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- PROCESS FOR PRODUCING PHOSPHOROAMIDITE
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The present invention provides high purity phosphoroamidite products by reducing the amount of impurities of triphosphite which has been additionally produced according to the conventional technique.Phosphoroamidites can be obtained with high purity such that the excess reaction is suppressed by using a reaction activator hardly generating triphosphite.According to the present invention, phosphoroamides can be obtained with high purity, which has heretofore been difficult to suppress the generation of impurities of triphosphite.
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Page/Page column 9
(2008/06/13)
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- PHOSPHITYLATION PROCESS
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A process for the phosphitylation of an alcohol or thiol with a phosphitylation agent in the presence of an activator is provided. The activator has the formula (1): wherein p is 0 or an integer from 1 to 4 and R for each occurrence is a substituent. Pref
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- Methods of producing phosphitylated compounds
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Provided are methods of producing phosphitylated compounds, including 3′-O-phosphoramidites, comprising the step of reacting a hydroxyl-containing compound with a phosphitylating agent in the presence of a phosphitylation activator selected from the group consisting of: (1) acid-base complexes derived from an amine base of Formula I 1wherein R, R1, and R2 are independently C1-C10 alkyl, C1-C10 cycloalkyl, C1-C10 aryl, C1-C10 aralkyl, C1-C10 heteroalkyl, or C1-C10 heteroaryl; (2) acid-base complexes derived from an amine base of Formula II 2wherein R3, R4, R5, R6, and R7 are independently hydrogen, C1-C10 alkyl, C1-C10 cycloalkyl, C1-C10 aryl, C1-C10 aralkyl, C1-C10 heteroalkyl, or C1-C10 heteroaryl, and at least one of R3, R4, R5 R6, and R7 is not hydrogen.; (3) acid-base complexes derived from a diazabicyclo amine base; (4) zwitterionic amine complexes; and (5) combinations of two or more thereof, to produce a phosphitylated compound.
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- Method of preparing phosphoramidites
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Improved methods for preparation of phosphoramidite compounds are disclosed. The phosphoramidites are useful, for example, for the preparation of oligonucleotides by solid state oligonucleotide synthetic regimes.
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- Improved process for the preparation of nucleosidic phosphoramidites using a safer and cheaper activator
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A new, simplified commercial process for the preparation of nucleosidic phosphoramidites, key raw materials for the automated solid-supported synthesis of oligonucleotide-based drugs, was developed. Phosphitylation of a variety of protected nucleosidic derivatives (1-4) with a small excess of 2-cyanoethyl-N,N,N′,N′-tetraisopropyl phosphoramidite (5, bis-reagent) and pyridinium trifluoroacetate (Py·TFA) as the activator in an appropriate solvent at room temperature formed 75-96% of desired nucleosidic phosphoramidite products in less than 2 h. An efficient nonaqueous work-up has been developed to further streamline the isolation of moisture-sensitive P(III) nucleosidic compounds. The key finding is the use of Py·TFA, which is effective, inexpensive, stable, less acidic (pKa 5.2) than 1H-tetrazole, nontoxic, safe, and highly soluble in organic solvents. The reaction mechanism for phosphitylation with Py TFA as an activator has also been studied. An improved, robust, and versatile process for the preparation of nucleotide phosphoramidites under very concentrated reaction conditions was developed to support commercial manufacture of oligonucleotide-based drugs.
- Sanghvi, Yogesh S.,Guo, Zhiqiang,Pfundheller, Henrik M.,Converso, Antonella
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p. 175 - 181
(2013/09/07)
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- Novel unique catalytic activating reagents in synthesis of biophosphates via the phosphoramidite route
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Trimethylchlorosilane (TMSCI) and 2,4-dinitrophenol are remarkably efficient activators in reaction of P(III) amides with nucleosides to give P(III) esters in excellent yield.
- Dabkowski, Wojciech,Tworowska, Izabela,Michalski, Jan,Cramer, Friedrich
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p. 1639 - 1644
(2007/10/03)
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- One-pot synthesis of deoxyadenosine 3'-thiophosphates
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A mild and efficient one-step method of thiophosphorylation was devised for acid-sensitive nucleosides. The procedure is based on thiophosphorylation of nucleoside magnesium alkoxide by 2-chloro-2-thio-1,3,2-dioxaphospholane. The utility and efficiency of
- Szczepanik, Maciej B.,De?saubry, Laurent,Johnson, Roger A.
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p. 7455 - 7458
(2007/10/03)
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- Trimethylchlorosilane: A novel activating reagent in nucleotide synthesis via the phosphoramidite route
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Trimethylchlorosilane (TMSCl) is a remarkably efficient activator in the reaction of phosphorus(III) amides with nucleosides to give phosphorus(III) esters in excellent yield.
- Dabkowski, Wojciech,Tworowska, Izabela,Michalski, Jan,Cramer, Friedrich
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p. 877 - 878
(2007/10/03)
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- A novel phosphitylating reagent for in situ generation of deoxyribonucleoside phosphoramidites
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A new phosphitylating reagent, 2-cyanoethoxy(N,N-diisopropylamino)3-nitro-1,2,4-triazolylphosphine (1), has been prepared and effectively used in in situ generation of 5'-DMT-nucleoside phosphoramidites and automated syntheses of oligonucleotides.
- Zhang, Zhaoda,Tang, Jin Yan
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p. 331 - 334
(2007/10/02)
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- Some Steric Aspects of Synthesis of Oligoribonucleotides by Phosphoramidite Approach on Solid Support
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The influence of 2'-O-substituents (i.e. methyl, tetrahydropyranyl, tert-butyldimethylsilyl) on the chemical synthesis of oligoribonucleotides by phosphoramidite approach on solid support is described and compared with respective 2'-deoxynucleoside derivative.The observations on reactivity of these different 2'-O-protected derivatives at phosphatilation and condensation steps show their strong hindrance dependence.Some other aspects like reactivity of tetrahydropyranyl diastereoisomers, 3'- and 2'-O-phosphoramidites and some chemical properties of 2'-O-(tert-butyldimethylsilyl) protecting group are also presented.
- Kierzek, Ryszard,Rozek, Marek,Markiewicz, Wojciech T.
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p. 507 - 516
(2007/10/02)
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- POLYMER-SUPPORTED SYNTHESIS OF DEOXYOLIGONUCLEOTIDES USING IN SITU PREPARED DEOXYNUCLEOSIDE 2-CYANOETHYL PHOSPHORAMIDITES
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The easily acessibile reagent 2-cyanoethyl-bis(diisopropylamino)phosphoramidite is shown to be suitable for the in-situ, 1H-tetrazole catalysed, preparation of d-nucleoside-3'-phosphoramidites.THe latter compounds could be applied successfuly as building blocks in a solid-phase DNA synthesis using an automated DNA synthesizer.
- Nielsen, J.,Marugg, J. E.,Taagaard, M.,Boom, J. H. van,Dahl, O.
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- β-CYANOETHYL N,N-DIALKYLAMINO/N-MORPHOLINOMONOCHLORO PHOSPHOAMIDITES, NEW PHOSPHITYLATING AGENTS FACILITATING EASE OF DEPROTECTION AND WORK-UP OF SYNTHESIZED OLIGONUCLEOTIDES
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β-Cyanoethyl monochlorophosphoamidites of the secondary amines N,N-dimethylamine, N,N-diisopropylamine and morpholine have been prepared which showed quantitative phosphitylation of the protected deoxynucleosides.The phosphitylated deoxynucleosides have successfully been used in the formation of internucleotidic bonds. β-Cyanoethyl nucleoside-3'-N,N-diisopropylphosphoamidites have saticfactorily been used for the synthesis of the oligodeoxynucleotide d(CGGTACCG).
- Sinha, N. D.,Biernat, J.,Koester, H.
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p. 5843 - 5846
(2007/10/02)
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