专利号:US-9920084-B2 优先权日:2011-08-23 标题 :Ionic tags for synthesis of oligoribonucleotides 发明人:DAMHA MASAD J; HASSLER MATTHEW; CHAN TAK-HANG; NANDYALA MALLIKARJUNA REDDY; DONGA ROBERT ALEXANDER 权利人:DAMHA MASAD J; HASSLER MATTHEW; CHAN TAK HANG; NANDYALA MALLIKARJUNA REDDY; DONGA ROBERT ALEXANDER; THE ROYAL INSTITUTION FOR THE ADVANCEMENT OF LEARNING/MCGILL UNIV; HONG KONG POLYTECHNIC UNIV 摘要:The invention relates to the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. In another aspect, the invention relates to compounds of formula (II) processes for making these compounds, and the use thereof in the chemical synthesis of oligonucleotides, e.g., oligoribonucleotides. The invention also relates to methods of synthesis of oligomers, including but not limited to oligopeptides, oligosaccharides and oligonucleotides, particularly oligoribonucleotides and also oligodeoxyribonucleotides, in solution systems, and ionic tag linkers for use in methods provided herein.
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: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.
专利号:WO-0206209-A1 优先权日:2000-07-19 标 题 :Synthesis method for n1,n3-bis (2.aminoethyl) propane-1,3-diamine, synthesis intermediates, resulting products and use thereof in synthesis of cyclam 发明人:HANDEL HENRI; BERNARD HELENE; ANTOINE MARINE 权利人:UNIV BRETAGNE OCCIDENTALE; HANDEL HENRI; BERNARD HELENE; ANTOINE MARINE 摘要:The invention concerns a method of synthesis of a linear polynitrogen-containing derivative, namely N1,N3-bis (2-aminoethyl) propane-1,3-diamine of general formula (I) using as synthesis intermediates compounds (II) and (III). The invention also concerns the resulting products and their use in the synthesis of cyclic polynitrogen-containing derivatives such as cyclam.
参考文献:10.1104/pp.109.148833 摘要:Finlayson SA, Krishnareddy SR, Kebrom TH, Casal JJ. Phytochrome regulation of branching in Arabidopsis. Plant Physiol. 2010 Apr;152(4):1914–27. 参考文献:10.3390/md9061133 摘要:Marino SD, Festa C, D’Auria MV, Cresteil T, Debitus C, Zampella A. Swinholide J, a Potent Cytotoxin from the Marine Sponge Theonella swinhoei. Marine Drugs. 2011 Jun 22;9(6):1133–41. doi: 10.3390/md9061133. 参考文献:10.1371/journal.pone.0021686 摘要:Santos MCT, Goldfeder MB, Zanchin NIT, Oliveira CC. The Essential Nucleolar Yeast Protein Nop8p Controls the Exosome Function during 60S Ribosomal Subunit Maturation. PLoS ONE. 2011 Jun 29;6(6):e21686. doi: 10.1371/journal.pone.0021686. 参考文献:10.1021/jp1121855 摘要:Wang L, Xu W, Khalizov AF, Zheng J, Qiu C, Zhang R. Laboratory investigation on the role of organics in atmospheric nanoparticle growth. J Phys Chem A. 2011 Aug 18;115(32):8940–7. doi: 10.1021/jp1121855. 参考文献:10.1107/s160053681101556x 摘要:Dogan HZ, Sengul A, Coles SJ. 1-[6-(6-Acetyl-pyridin-2-yl)pyridin-2-yl]ethanone. Acta Crystallogr Sect E Struct Rep Online. 2011 Jun 01;67(Pt 6):o1295.