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-6531591-B1 优先权日:1999-07-07 标 题 :Synthesis of stable quinone and photoreactive ketone phosphoramidite reagents for solid phase synthesis of photoreactive-oligomer conjugates 发明人:FENSHOLDT JEF 权利人:EXIQON AS 摘要:Quinone phosphoramidite reagents as well as photoreactive ketone phosphoramidite reagents, such as anthraquinone phosphoramidite reagents and benzophenone phosphoramidite reagents were synthesized and used for the solid phase synthesis of photoreactive-oligonucleotide conjugates. These phosphoramidite reagents are stable, suitable for large-scale synthesis and designed for automated solid phase synthesis of oligomers terminating in a photoreactive moiety.
专利号:EP-1202998-B1 优先权日:1999-07-07 标 题 :Synthesis of stable quinone and photoreactive ketone phosphoramidite reagents for solid phase synthesis of photoreactive-oligomer conjugates 发明人:FENSHOLDT JEF 权利人:EXIQON AS 摘要:Quinone phosphoramidite reagents as well as photoreactive ketone phosphoramidite reagents, such as anthraquinone phosphoramidite reagents and benzophenone phosphoramidite reagents were synthesized and used for the solid phase synthesis of photoreactive-oligonucleotide conjugates. These phosphoramidite reagents are stable, suitable for large-scale synthesis and designed for automated solid phase synthesis of oligomers terminating in a photoreactive moiety.
专利号:US-12146136-B2 优先权日:2020-03-26 标题:Synthesis of modified oligonucleotides with increased stability 发明人:KHVOROVA ANASTASIA; ROUX LOÃ?C MAURICE RENÉ JEAN; YAMADA KEN 权利人:UNIV MASSACHUSETTS 摘要:This disclosure relates to the synthesis of novel modified oligonucleotides. The synthesis of novel phosphoramidites are also provided.
专利号:EP-0901500-B1 优先权日:1996-05-03 标题:In situ preparation of nucleoside phosphoramidites and their use in synthesis of oligonucleotides 发明人:ZHANG ZHAODA; TANG JIN-YAN 权利人:AVECIA BIOTECHNOLOGY INC 摘要:The invention provides novel bifunctional phosphitylating reagents and their application in in situ preparation of 5'-protected nucleoside phosphoramidites and synthesis of oligonucleotides. Bifunctional phosphitylating reagents according to the invention react quickly with nucleosides under weakly acidic conditions. In addition, the bifunctional phosphitylating reagents according to the invention generate chemoselectively the corresponding nucleoside phosphoramidites in situ, without need to purify the nucleoside phosphoramidites before using them in oligonucleotide synthesis. Finally, the bifunctional phosphitylating reagents according to the invention are relatively stable and easy to handle.
参考标题:Synthesis And Properties Of Aminoacylamido-Amp: Chemical Optimization For The Construction Of An N-Acyl Phosphoramidate Linkage 作者:Tomohisa Moriguchi,Terukazu Yanagi,Masao Kunimori,Takeshi Wada,Mitsuo Sekine |发布日期:2000.12.1 摘要:This Paper Describes The Design And Synthesis Of A New Type Of Aminoacyl-Adenylate Analogue (Aa-Ampn) Having An N-Acyl Phosphoramidate Linkage Where The Oxygen Atom Of The Mixed Anhydride Bond Of Aminoacyl-Adenylate (Aa-Amp) Is Replaced By An Amino Group. This New Type Of Aa-Amp Analogue Is Expected To Be Useful As Material For Studies On The Recognition Mechanism Of The Aminoacylation Of Trna And
合成参考文献
摘要:Stankevič, M.; Pietrusiewicz, K. M., Science of Synthesis, (2009) 42, 304.