合成目标产物 Cytidine 主要起始原料 Beta-D-Ribofuranose (9CI) And Cytosine
2536-99-4 = 65-46-3 + 84-52-6 反应条件:1.1 Reagents: Cupric Chloride Solvents: Dimethyl Sulfoxide,Water; Ph 8.8,50 °C 标题:Ribonuclease Activity Of An Artificial Catalyst That Combines A Ligated Cuii Ion And A Guanidinium Group At The Upper Rim Of A Cone-Calix[4]Arene Platform 作者:Salvio,Riccardo; Et Al 参考文献:Journal Of Organic Chemistry 日期:2015 卷标:80(11) 页码:5887-5893]
2536-99-4 = 65-46-3 + 84-52-6 + 85-94-9 反应条件:1.1 Reagents: 4-(2-Hydroxyethyl)-1-Piperazineethanesulfonic Acid Catalysts: Manganese,Dichloro(2,2′:6′,2′′-Terpyridine-Kn1,Kn1′,Kn1′′)-,(Sp-5-12)- Solvents: Water; 21 H,Ph 7.0,50 °C1.2 Reagents: Phosphoric Acid Solvents: Water 标题:Hydrolysis Of Di-Ribonucleoside Monophosphate Diesters Assisted By A Manganese(Ii) Complex 作者:Yashiro,Morio; Et Al 参考文献:Bulletin Of The Chemical Society Of Japan 日期:2003 卷标:76(9) 页码:1813-1817
专利号:US-6683189-B1 优先权日:1996-02-26 标 题 :Method for the synthesis of pyrrole and imidazole carboxamides on a solid support 发明人:DERVAN PETER B; BAIRD ELDON 权利人:CALIFORNIA INST OF TECHN 摘要:The present invention describes a novel method for the solid phase synthesis of polyamides containing imidazole and pyrrole carboxamides. The polyamides are prepared on a solid support from aromatic carboxylic acids and aromatic amines with high stepwise coupling yields (>99%), providing milligram quantities of highly pure polyamides. The present invention also describes the synthesis of analogs of the natural products Netropsin and Distamycin A, two antiviral antibiotics. The present invention also describes a novel method for the solid phase synthesis of imidazole and pyrrole carboxamide polyamide-oligonucleotide conjugates. This methodology will greatly increase both the complexity and quantity of minor-groove binding polyamides and minor-groove binding polyamide-oligonucleotide conjugates which can be synthesized and tested.
专利号:US-9884885-B2 优先权日:2009-05-18 标题:Synthesis of labile base protected-modified deoxy and modified ribo nucleosides, corresponding phosphoramidites and supports and their use in high purity oligonucleotide synthesis 发明人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P 权利人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P; CHEMGENES CORP 摘要:This invention relates to novel method of synthesis of RNA utilizing N-2-acetyl protected guanine as nucleoside base, nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-acetyl protected guanine as nucleoside base protecting group, which is significantly faster base labile protecting group, yet significantly more stable than commonly utilized-2-isobutyryl guanosine is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups, including acetyl group from guanine and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of acetyl protecting groups of the natural deoxy and ribonucleosides occurs under substantially reduced time in contact with mild deprotection conditions such as mild bases, secondary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application. This approach is designed to lead to high purity large scale therapeutic grade oligonucleotide chimeras which consist of fluoro sugar modification in conjunction with deoxy nucleosides, ribonucleosides, modified base and modified sugar nucleosides. This approach is further designed to use acetyl guanine protecting group when other bases are sensitive nucleoside, and for use in oligo peptide synthesis and for support bound oligo nucleotides.
专利号:WO-2024185734-A1 优先权日:2023-03-03 标 题:Polyphosphorylated nucleoside, phosphate-activated nucleotide used for synthesis of polyphosphorylated nucleoside and method for synthesis of same, and method for synthesis of polyphosphorylated nucleoside using phosphate-activated nucleotide 发明人:KATAOKA MASANORI; FUKUI CHIHARU; TSUJI YOHEI; FUJIMURA Kazuma 权利人:NATIAS INC 摘要:The present invention provides: a polyphosphorylated nucleoside which has a structure represented by formula (I) and can be efficiently produced by a short process and a simple operation with use of a less expensive material; a phosphate-activated nucleotide which is used for the synthesis of the polyphosphorylated nucleoside and a method for the synthesis of this phosphate-activated nucleotide; and a method for the synthesis of a polyphosphorylated nucleoside using a phosphate-activated nucleotide. In the formula, B represents a protected or unprotected, natural or artificial nucleoside base; R 1 , R 2 , R 4 and R 5 each represent H or an alkyl group or the like, and R 1 , R 2 , R 4 and R 5 may be the same as or different from each other; X and Y each represents H, OH, OCH 3 or the like; h represents an integer of 1 to 3; p, n, m and q each represent 0 or an integer, and p, n, m and q are in no particular order; and (p + n + m + q) is an integer of 0 to 5,000.
专利号:US-8981076-B2 优先权日:2008-11-29 标 题 :Synthesis of N-FMOC protected deoxy nucleosides, ribo nucleosides, modified deoxy and ribo nucleosides, and phosphoramidites, and their use in oligonucleotide synthesis 发明人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P 权利人:SRIVASTAVA SURESH C; SRIVASTAVA NAVEEN P; CHEMGENES CORP 摘要:This invention relates to synthesis of novel -N-FMOC protected nucleosides, succinates, phosphoramidites, corresponding solid supports that are suitable for oligo deoxy nucleosides and RNA oligonucleotide synthesis. Our discovery using N-FMOC as nucleoside base protecting group, which is highly base labile protecting group is a novel approach to obtain highest purity oligonucleotides. This approach is designed to lead to very high purity and very clean oligonucleotide, after efficient removal of the protecting groups and to produce high purity therapeutic grade DNA oligonucleotides, RNA oligonucleotides, diagnostic DNA, diagnostic RNA for microarray platform. The deprotection of FMOC protecting groups of the natural deoxy and ribonucleosides occurs under very mild deprotection conditions such as mild bases, secondary and tertiary amines for removal of such groups under such conditions would allows synthesis of various DNA and RNA of highest purity for diagnostics and therapeutic application. This approach is further designed to use FMOC protecting group on various base sensitive nucleoside, and for use in oligo peptide synthesis and for support bound oligo nucleotides. DNA oligonucleotides containing 3′-end dA at the 3′-terminal will be produced using the FMOC-dA-supports would lead to much reduced M−1 deletion sequences, and thereby high purity.
专利号:US-8138330-B2 优先权日:2006-09-11 标 题 :Process for the synthesis of oligonucleotides 发明人:LEUCK MICHAEL; WOLTER ANDREAS; STUMPE ALFRED 权利人:LEUCK MICHAEL; WOLTER ANDREAS; STUMPE ALFRED; SIGMA ALDRICH CO LLC 摘要:The present invention discloses novel methods for the synthesis of oligonucleotides with nucleoside phosphoramidites on solid supports. The methods comprise the stepwise chain assembly of oligonucleotides on supports with 5′-acyl phosphoramidites. The synthesis cycles consist of a front end deprotection step which is conducted with a solution of a primary amine or a phenolate, a phosphoramidite coupling step with a 5′-acyl nucleoside phosphoramidite in the presence of an activator, a phosphite oxidation step and an optional capping step. The novel methods improve the quality of synthetic oligonucleotides due to the irreversibility of the front end deprotection step, which prevents the formation of deletion sequences, and due to the avoidance of acidic reagents in the synthesis cycles, which prevent the formation of depurination side products. The invention further discloses novel nucleoside phosphoramidite compositions wherein the phosphoramidites carry acyl front end protective groups which are cleavable with primary amines or phenolates. The invention is applicable to the synthesis of oligodeoxyribonucleotides, oligoribonucleotides and oligonucleotides with modifications in their sugar or phosphate groups.
专利号:US-7329515-B2 优先权日:2003-04-21 标题 :Solid support for the synthesis of 3′-amino oligonucleotides 发明人:LEUCK MICHAEL; WOLTER ANDREAS 权利人:SIGMA ALDRICH CO 摘要:The present invention discloses novel methods and solid supports for the synthesis of 3′-amino oligonucleotides. The novel supports are based on an unsubstituted or ring-substituted hydroxymethylbenzoyl linker element wherein the hydroxymethyl group is esterified to a solid phase bound carboxylic acid and the carbonyl group is linked to an amino alcohol as an amide. Oligonucleotides are conveniently synthesized on the novel supports with no modifications in the standard phosphoramidite synthesis scheme. The ester function of the support is cleaved under the alkaline deprotection conditions for oligonucleotides to provide a free hydroxymethyl group that aids in the release of the 3′-amino oligonucleotide products with a free amino group through neighbor group participation. The free amino group of the oligonucleotides is available for further conjugation reactions to haptens, reporter groups, surfaces or other small molecules or biomolecules. The methods provided are particularly mild, do not require any modifications in standard protocols for the synthesis and deprotection of oligonucleotides, provide the 3′-amino oligonucleotides free of side products and do not introduce chiral centers to the oligonucleotides.
1. Arango, D., Sturgill, D., Alhusaini, N., et al. Acetylation of cytidine in mRNA promotes translation efficiency. Cell 175(7), 1872-1886 (2018). 2. Nakano, S., Suzuki, T., Kawarada, L., et al. NSUN3 methylase initiates 5-formylcytidine biogenesis in human mitochondrial tRNAMet. Nat. Chem. Biol. 12(7), 546-551 (2016).
合成参考文献
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