118362-03-1Relevant articles and documents
Microwave-assisted preparation of nucleoside-phosphoramidites
Meher,Efthymiou,Stoop,Krishnamurthy
supporting information, p. 7463 - 7465 (2014/07/07)
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.
Synthesis of cyclic di-nucleotidic acids as potential inhibitors targeting diguanylate cyclase
Ching, Shi Min,Tan, Wan Jun,Chua, Kim Lee,Lam, Yulin
experimental part, p. 6657 - 6665 (2010/10/21)
Five analogs of cyclic di-nucleotidic acid including c-di-GMP were synthesized and evaluated for their biological activities on Slr1143, a diguanylate cyclase of Synechocystis sp. Slr1143 was overexpressed from the recombinant plasmid which contained the gene of interest and subsequently purified by affinity chromatography. A new HPLC method capable of separating the compound and product peaks with good resolution was optimized and applied to the analysis of the compounds. Results obtained show that cyclic di-inosinylic acid 1b demonstrates a stronger inhibition on Slr1143 than c-di-GMP and is a potential inhibitor for biofilm formation.
Methods of producing phosphitylated compounds
-
Page 6-7, (2008/06/13)
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.
Methods for synthesizing nucleosides, nucleoside derivatives and non-nucleoside derivatives
-
, (2008/06/13)
The present invention provides methods for the chemical synthesis of nucleosides and derivatives thereof, including 2′-amino, 2′-N-phthaloyl, 2′-O-methyl, 2′-O-silyl, 2′OH nucleosides, C-nucleosides, nucleoside phosphoramidites, C-nucleoside phosphoramidites, and non-nucleoside derivatives.
Methods for synthesizing nucleosides, nucleoside derivatives and non-nucleoside derivatives
-
, (2008/06/13)
The present invention provides methods for the chemical synthesis of nucleosides and derivatives thereof, including 2′-amino, 2′-N-phthaloyl, 2′-O-methyl, 2′-O-silyl, 2′-O-triisopropylsilyloxymethyl, 2′-OH nucleosides, C-nucleosides, nucleoside phosphoramidites, C-nucleoside phosphoramidites, and non-nucleoside derivatives.
An improved synthesis of the dinucleotides pdCpA and pdCpdA
Zhu, Xue-Feng,Scott, A. Ian
, p. 197 - 211 (2007/10/03)
An improved route was developed for the preparation of the dinucleotide hybrid 5′-O-phosphoryl-2′-deoxycytidylyl-(3′ → 5′)adenosine (pdCpA) 7. This simple and concise synthesis involves the successive coupling of 2-cyanoethyl N, N, N′, N′-tetra- isopropylphosphorodiamidite with 4-N-benzoyl-5′-O-(4,4′-dimethoxytrityl)-2′-deoxy-cytidine 1 and 6-N,6-N,2′-O,3′-O-tetrabenzoyladenosine 2 as the key step. Some dinucleotide derivatives bearing different protecting groups were also synthesized and the selective deprotection conditions were studied in detail. The utility and efficiency of this approach has been further demonstrated by its application to the synthesis of total DNA dinucleotide pdCpdA 17 and total RNA dinucleotide 21.
Improved process for the preparation of nucleosidic phosphoramidites using a safer and cheaper activator
Sanghvi, Yogesh S.,Guo, Zhiqiang,Pfundheller, Henrik M.,Converso, Antonella
, p. 175 - 181 (2013/09/07)
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.
New Nucleoside Phosphoramidites and Coupling Protocols for Solid-Phase RNA Synthesis
Lyttle, Matthew H.,Wright, Peter B.,Sinha, Nanda D.,Bain, J. D.,Chamberlin, A. Richard
, p. 4608 - 4615 (2007/10/02)
The 5'-O-(4,4'-dimethoxytrityl)-2'-O-(trialkylsilyl)ribonucleoside 3'-O-(2-cyanoethyl N,N-diethylphosphoramidites) 3, 5, 7, and 9, modified monomers for RNA synthesis, were prepared from 2-cyanoethyl N,N-diethylchlorophosphoramidite (1).In conjunction with newly developed coupling protocols for automated solid-phase synthesis, they afforded synthetic oligoribonucleotides up to 74 base units in length.The performance of the new compounds was compared to the analogous 5'-O-(4,4'-dimethoxytrityl)-2'-O-(trialkylsilyl)ribonucleoside 3'-O-(2-cyanoethyl N,N-diisopropylphosphoramidites) 4, 6, 8, and 10.Complete removal of benzoyl groups from N2-benzoylguanosine, which was incorporated into some of the synthetic oligoribonucleotides, was demonstrated.Purification procedures by reverse phase HPLC and PAGE methods are also presented.
Some Steric Aspects of Synthesis of Oligoribonucleotides by Phosphoramidite Approach on Solid Support
Kierzek, Ryszard,Rozek, Marek,Markiewicz, Wojciech T.
, p. 507 - 516 (2007/10/02)
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.
