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-8193384-B2 优先权日:2005-07-29 标 题 :Polymer-bound phosphitylating reagents for the synthesis of organophosphorus compounds 发明人:PARANG KEYKAVOUS; AHAMDIBENI YOUSEF 权利人:PARANG KEYKAVOUS; AHAMDIBENI YOUSEF; RHODE ISLAND EDUCATION 摘要:The synthesis and biochemical utility of modified oligonucleotides containing diphosphodiester internucleotide linkages. The synthesis of these compounds was carried out using diphosphitylating reagents. Oligonucleotides containing diphosphate diester bridges wherein said oligonucleotides are synthesized via a solid-phase synthesis strategy to form modified oligonucleotides. Diphosphitylating, triphosphitylating, tetraphosphitylating, β-triphosphitylating, bifunctional diphosphitylating, bifunctional triphosphitylating, and bifunctional tetraphosphitylating reagents wherein, the phosphorus atoms are linked together through oxygen, sulfur, amino, or methylene groups and/or are substituted with chlorine, diisopropylamine and cyanoethoxy groups.
专利号:US-2004152905-A1 优先权日:2003-01-31 标题:Universal building blocks and support media for synthesis of oligonucleotides and their analogs 发明人:GUZAEV ANDREI P; MANOHARAN MUTHIAH 摘要:Compounds for the synthesis of oligomeric compounds, particularly oligonucleotides and chemically modified oligonucleotide analogs, are provided. In addition, methods for functionalization of a support medium with a first monomeric subunit and methods for the synthesis of oligomeric compounds utilizing the novel compounds bound to support media are provided.
专利号:US-2004242897-A1 优先权日:2002-07-31 标题 :Universal support media for synthesis of oligomeric compounds 发明人:GUZAEV ANDREI P; MANOHARAN MUTHIAH 摘要:Compounds for the synthesis of oligomeric compounds, particularly oligonucleotides and oligonucleotide mimetics, are provided. In addition, methods for functionalizing a support medium with a first monomeric subunit and methods for the synthesis of oligomeric compounds utilizing the novel compounds bound to support media are provided.
专利号:US-6117992-A 优先权日:1996-08-26 标题 :Reagents and process for synthesis of oligonucleotides containing phosphorodithioate internucleoside linkages 发明人:IYER RADHAKRISHNAN P 权利人:HYBRIDON INC 摘要:The invention provides new methods for synthesizing oligonucleotides containing at least one, and preferably all phosphorodithioate internucleoside linkages with less than 5% phosphoromonothioate contamination. This level of purity in the synthesis of phosphorodithoates has previously been very difficult to achieve with all existing methods. The invention further provides phosphorothioamidite nucleoside synthons comprising a sulfur protecting group that is stable under normal oligonucleotide synthesis conditions.
专利号:US-10253153-B2 优先权日:2015-04-24 标题 :Linker and support for solid phase synthesis of nucleic acid, and production method of nucleic acid using said support 发明人:MAETA ERI; MORI KENJIRO; HORIE SHOHEI; ITO TAKAHIKO; SAITO SHOICHIRO; NAGAO RYUHEI 权利人:NITTO DENKO CORP 摘要:The present invention provides a linker for solid phase synthesis of nucleic acid, which consists of a compound represented by the formula (I) or the formula (II), a support for solid phase synthesis of nucleic acid, which has a structure represented by the formula (III), and a production method of a nucleic acid, which uses the support: n nwherein each symbol is as defined in the SPECIFICATION.
1: Manoharan M, Lu Y, Casper MD, Just G. Allyl group as a protecting group for internucleotide phosphate and thiophosphate linkages in oligonucleotide synthesis: facile oxidation and deprotection conditions. Org Lett. 2000 Feb 10;2(3):243-6. 3: Lesiak K, Khamnei S, Torrence PF. 2',5'-Oligoadenylate:antisense chimeras--synthesis and properties. Bioconjug Chem. 1993 Nov-Dec;4(6):467-72.
合成参考文献
摘要:Kashemirov, B. A.; Błażewska, K.; Justyna, K.; Lyu, J.; McKenna, C. E., Science of Synthesis Knowledge Updates, (2021) 1, 475. 摘要:Kashemirov, B. A.; Błażewska, K.; Justyna, K.; Lyu, J.; McKenna, C. E., Science of Synthesis Knowledge Updates, (2021) 1, 433.