74405-40-6Relevant articles and documents
Liquid-phase RNA synthesis by using alkyl-chain-soluble support
Kim, Shokaku,Matsumoto, Masanori,Chiba, Kazuhiro
supporting information, p. 8615 - 8620 (2013/07/26)
Recent progress in the RNA therapeutics has increased demand for the synthesis of large quantities of oligoribonucleotides. The assembly of RNA oligomers relies mainly on solid-phase approaches. These allow rapid product purification and the ability to drive a target reaction to completion through the use of excess reagents. Despite the known advantages of solid-phase synthesis, some issues in the process remain to be addressed, such as low and limited scale, reagent accessibility, and the use of a very large excess of reagents. Herein, we report a highly efficient and practical method of liquid-phase synthesis of RNA oligomers by using alkyl-chain-soluble support. We demonstrate the utility of the liquid-phase method through 21-mer RNA synthesis on a gram scale. The assembly of RNA oligomers relies principally on solid-phase approaches, although some alternative methods have been developed to date. A highly efficient and practical method of liquid-phase synthesis for RNA oligomers by using an alkyl-chain-type soluble support is reported. The utility of the liquid-phase method through 21-mer RNA synthesis on a gram scale is described (see scheme). Copyright
High yield detritylation of surface-attached nucleosides with photoacid generated in an overlying solid film: Roles of translational diffusion and scavenging
Garland, Peter B.,Serafinowski, Pawel J.
experimental part, p. 451 - 459 (2009/07/18)
Conventional solid-phase oligonucleotide synthesis overcomes the reversibility of acid-dependent detritylation by washing away the released dimethoxytrityl cations (DMT+) with acid. This option is unavailable if the acid is photogenerated in an overlying solid film, as in the photolithographic fabrication of oligonucleotide arrays on planar surfaces. To overcome the resulting reversibility problem we developed methods of achieving ≥98% detritylation of glass-attached 5′-O-DMT-thymidine, a model for 5′-O-DMT-protected oligonucleotides, by the photogeneration of trichloroacetic acid in a solid film. Enhanced intrafilm diffusion, insufficient to degrade the photolithographic resolution but enabling DMT+ to move from its plane of release into the overlying photoacid-generating film, increased detritylation from ≤30% to ≥98%. Inclusion of an intrafilm carbocation scavenger such as a triarylsilane hydride converted the detritylation into a time-dependent irreversible process proceeding to ≥99% detritylation within 60 s following brief photoacid generation. Light sensitivity is high, exceeding direct photodeprotection methods by 15-100 fold. The Royal Society of Chemistry 2009.
Solid Phase Synthesis of Oligodeoxyribonucleotides Utilizing the Phenylthio Group as a Phosphate Protecting Group
Matsuzaki, Jun-ichi,Kohno, Kyoko,Tahara, Shin-ichiro,Sekine, Mitsuo,Hata, Tsujiaki
, p. 1407 - 1414 (2007/10/02)
Oligodeoxyribonucleotide synthesis utilizing the phenylthio group as a phosphate protecting group was applied to the solid phase method.The base residues of deoxyguanosine and deoxyadenosine were protected with bis(isobutyryloxy)ethylene (Bibe) and phthaloyl groups to avoid the base modfication and depurination, respectively.A key synthetic intermediate of N2-isobutyryl-N1,N2-bis(isobutyryloxy)ethylenedeoxyguanosine was prepared in high yield by four-step reaction from deoxyguanosine and used for preparation of the building blocks of deoxyguanosine required for the polymer support synthesis.Two kinds of polymer supports, i.e., 1 percent cross-linked polystyrene and controlled pore glass were chosen.The latter was employed for the synthesis of dodecadeoxyribonucleotides by using an automated DNA synthesizer.
