3',5'-di-O-benzyl-4'-C-(p-toluenesulfonyloxyethyl)-2'-O-acetyl-5-methyluridine | 287737-66-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3',5'-di-O-benzyl-4'-C-(p-toluenesulfonyloxyethyl)-2'-O-acetyl-5-methyluridine
• 英文别名: 2'-O-Acetyl-3',5'-di-O-benzyl-4'-p-toluenesulfonyloxyethyl-5-methyluridine；[(2R,3R,4S,5R)-2-(5-methyl-2,4-dioxopyrimidin-1-yl)-5-[2-(4-methylphenyl)sulfonyloxyethyl]-4-phenylmethoxy-5-(phenylmethoxymethyl)oxolan-3-yl] acetate
• CAS: 287737-66-0
• 化学式: C₃₅H₃₈N₂O₁₀S
• 分子量: 678.76
• InChiKey: MCLPQNOUFAWGOE-DVFPCMIBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  48
• 可旋转键数：
  15
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  155
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3',5'-di-O-benzyl-4'-C-(p-toluenesulfonyloxyethyl)-2'-O-acetyl-5-methyluridine 在 palladium dihydroxide 吡啶 、 sodium hydroxide 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 10.25h， 生成 1-(2,6-anhydro-4-{[bis(4-methoxyphenyl)(phenyl)-methoxy]methyl}-5-deoxy-α-L-lyxohexofuranosyl)-5-methylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  作为有效的反义寡核苷酸的2'-O，4'-C-亚乙基桥核酸（ENA）的合成和性质。

  摘要：

  合成了新型双环核苷，2'-O，4'-C-乙烯核苷和2'-O，4'-C-丙烯核苷，作为反义寡核苷酸的构建基块，以进一步优化2'-O，4'-桥连核酸（2'，4'-BNA）或锁定核酸（LNA）的C-亚甲基键。这些核苷中的2'-O，4'-C-乙烯-和丙烯键都将糖的褶皱限制为RNA的N-构象，就像2'，4'-BNA / LNA一样。此外，具有2'-O，4'-C-乙烯核苷的乙烯桥连核酸（ENA）大大提高了对互补RNA的亲和力，并且与2'，4'-BNA / LNA（DeltaT （m）＝ + 3，每次修改约5摄氏度。另一方面，添加2'-O，4' 寡核苷酸中的-C-丙烯修饰导致与互补RNA的亲和力降低。至于对核酸酶的稳定性，在寡核苷酸中掺入一个2'-O，4'-C-乙烯或一个2'-O，4'-C-丙烯核苷可显着提高其对核酸外切酶的抗性至大于2'的程度。 ，4'-BNA / LNA。这些结果表明ENA比2'，4'-BNA

  DOI：

  10.1016/s0968-0896(03)00115-9
• 作为产物：
  描述：

  (3aR,5R,6S,6aR)-6-(benzyloxy)-5-((benzyloxy)methyl)-2,2-dimethyl-5-vinyltetrahydrofuro[2,3-d][1,3]dioxole 在 9-borabicyclo[3.3.1]nonane dimer 、 三氟甲磺酸三甲基硅酯 、 硫酸 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 、 1,2-二氯乙烷 为溶剂， 生成 3',5'-di-O-benzyl-4'-C-(p-toluenesulfonyloxyethyl)-2'-O-acetyl-5-methyluridine
  参考文献：
  名称：

  2′-O,4′-C-ethylene-bridged nucleic acids (ENA): highly nuclease-resistant and thermodynamically stable oligonucleotides for antisense drug

  摘要：

  To develop antisense oligonucleotides, novel nucleosides, 2'-O-4'-C-ethylene nucleosides and their corresponding phosphoramidites, were synthesized as building blocks. The H-1 NMR analysis showed that the 2'-O,4'-C-ethylene linkage of these nucleosides restricts the sugar puckering to the N-conformation as well as the linkage of 2'-O,4'-C-methylene nucleosides which are known as bridged nucleic acids (BNA) or locked nucleic acids (LNA). The ethylene-bridged nucleic acids (ENA) showed a high binding affinity for the complementary RNA strand (DeltaT(m) = +5.2 degreesC/modification) and were more nuclease-resistant than natural DNA and BNA/LNA. These results indicate that ENA have better properties as antisense oligonucleotides than BNA/LNA. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00683-7

文献信息

• Synthesis of 2′,4′-Propylene-Bridged (Carba-ENA) Thymidine and Its Analogues: The Engineering of Electrostatic and Steric Effects at the Bottom of the Minor Groove for Nuclease and Thermodynamic Stabilities and Elicitation of RNase H
  作者：Yi Liu、Jianfeng Xu、Mansoureh Karimiahmadabadi、Chuanzheng Zhou、Jyoti Chattopadhyaya

  DOI：10.1021/jo101207d

  日期：2010.11.5

  any, effect on nuclease resistance but 8′S-OH resulted in significantly decreased nucleolytic stability; and (3) 8′-NH2 substituted carba-ENA leads to obvious loss in the nuclease resistance. The RNA strand in all of the carba-ENA derivatives modified AON:RNA hybrid duplexes can be digested by RNase H1 with high efficiency, even at twice the rate of those of the native and ENA modified counterpart.

  2'，4'-丙烯桥胸苷（carba-ENA-T）和5个8'-Me / NH 2通过将分子内自由基加成到束缚的肟-醚的C═N中，已经制备了/ OH修饰的氨基-ENA-T类似物。这些碳烯-ENA核苷随后被掺入15mer寡脱氧核苷酸（AON）中，并且与天然和ENA对应物相比，已研究了它们对cDNA和RNA的亲和力，核酸酶抗性和RNase H募集能力。这些碳烯-ENA修饰的AON具有高度的RNA选择性，因为它们都对AON：RNA双链体产生轻微的热稳定作用，但对AON：DNA双链体产生相当大的去稳定作用。发现在carba-ENA-T上不同的C8'取代基（在小凹槽的底部）仅导致AON：RNA双链体的热稳定性变化很小。但是，我们 观察到，亲代碳酸酯-ENA-T修饰的AONs表现出比ENA-T修饰的对应物更高的核酸分解稳定性。不仅取决于化学性质，而且取决于C8'取代基的立体化学取向，C8'取代基还可以进一
• Novel nucleoside and oligonucleotide analogues
  申请人：SANKYO COMPANY, LIMITED

  公开号：US20020147332A1

  公开（公告）日：2002-10-10

  A compound of the formula (1): 1 wherein R 1 and R 2 are the same or different and represent a hydrogen atom, a hydroxyl protecting group, a phosphate group, or —P(R 3 )R 4 , wherein R 3 and R 4 are the same or different and represent a hydroxyl group, an amino group, an alkoxy group having from 1 to 4 carbon atoms, a cyanoalkoxy group having from 1 to 5 carbon atoms or an amino group substituted by an alkyl group having from 1 to 4 carbon atoms; A represents an alkylene group having from 1 to 4 carbon atoms and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group, a substituted purin-9-yl group or a substituted 2-oxo-pyrimidin-1-yl group having a substituent &agr; selected from the group consisting of a hydroxyl group which may be protected, an alkoxy group having from 1 to 4 carbon atoms, a mercapto group which may be protected, an alkylthio group having from 1 to 4 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms, an amino group which may be protected, a mono- or di-alkylamino group which may be substituted by an alkyl group having from 1 to 4 carbon atoms, an alkyl group having from 1 to 4 carbon atoms and a halogen atom; or a salt thereof.

  化合物的式子（1）：1其中R1和R2相同或不同，表示氢原子，羟基保护基，磷酸基或-P（R3）R4，其中R3和R4相同或不同，表示羟基，氨基，具有1至4个碳原子的烷氧基，具有1至5个碳原子的氰基烷氧基或被1至4个碳原子的烷基取代的氨基; A表示具有1至4个碳原子的烷基，B表示嘌呤-9-基，2-氧代嘧啶-1-基，取代的嘌呤-9-基或取代的2-氧代嘧啶-1-基，具有α取代基，所述α取代基选自羟基（可能被保护），具有1至4个碳原子的烷氧基，巯基（可能被保护），具有1至4个碳原子的烷硫基，具有1至4个碳原子的烷氧基，氨基（可能被保护），可以被1至4个碳原子的烷基取代的单烷基或双烷基氨基，具有1至4个碳原子的烷基和卤原子; 或其盐。
• NOVEL NUCLEOSIDES AND OLIGONUCLEOTIDE ANALOGUES
  申请人：Sankyo Company, Limited

  公开号：EP1152009A1

  公开（公告）日：2001-11-07

  [Subject] The object of the present invention is to provide novel oligonucleotide analogues, which exhibit antisense or antigene activity having excellent stability, or exhibit excellent activity as a detection agent (probe) for a specific gene or as a primer for starting amplification, and to novel nucleoside analogues which are intermediates for their production. [Solution] A compound of the formula (1): [wherein R1 and R2 are the same or different and represent a hydrogen atom, a hydroxyl protecting group, a phosphoric acid group, or -P(R3)R4 [wherein R3 and R4 are the same or different and represent a hydroxyl group, an amino group, an alkoxy group having from 1 to 4 carbon atoms, a cyanoalkoxy group having from 1 to 5 carbon atoms or an amino group substituted by an alkyl group having from 1 to 4 carbon atoms]; A represents an alkylene group having from 1 to 4 carbon atoms; and B represents a purin-9-yl group, a 2-oxo-pyrimidin-1-yl group or a substituted purin-9-yl group or a substituted 2-oxo-pyrimidin-1-yl group having a substituent selected from the following α group]; or the salt thereof; (α group) a hydroxyl group which may be protected, an alkoxy group having from 1 to 4 carbon atoms, a mercapto group which may be protected, an alkylthio group having from 1 to 4 carbon atoms, an alkoxy group having from 1 to 4 carbon atoms, an amino group which may be protected, a mono- or di-alkylamino group which may be substituted by an alkyl group having from 1 to 4 carbon atoms, an alkyl group having from 1 to 4 carbon atoms and a halogen atom. A compound of the formula (I), and the pharmacologically acceptable salts or derivatives thereof.

  主题 本发明的目的是提供新型寡核苷酸类似物，它们具有优异的稳定性，表现出反义或反基因活性，或作为特定基因的检测剂（探针）或作为起始扩增的引物表现出优异的活性，以及作为其生产中间体的新型核苷类似物。 [解决方案］ 式（1）的化合物： [其中 R1 和 R2 相同或不同，代表氢原子、羟基保护基团、磷酸基团或 -P(R3)R4 [其中 R3 和 R4 相同或不同，代表羟基、氨基、具有 1 至 4 个碳原子的烷氧基、具有 1 至 5 个碳原子的氰基烷氧基或被具有 1 至 4 个碳原子的烷基取代的氨基]； A 代表具有 1 至 4 个碳原子的亚烷基；以及 B 代表嘌呤-9-基、2-氧代嘧啶-1-基或取代的嘌呤-9-基或取代的 2-氧代嘧啶-1-基，其取代基选自以下 α 基团]； 或其盐； (α 基团) 可被保护的羟基、具有 1 至 4 个碳原子的烷氧基、可被保护的巯基、具有 1 至 4 个碳原子的烷硫基、具有 1 至 4 个碳原子的烷氧基、可被保护的氨基、可被具有 1 至 4 个碳原子的烷基、具有 1 至 4 个碳原子的烷基和卤素原子取代的单-或二-烷基氨基。式（I）化合物及其药理学上可接受的盐或衍生物。
• Oligonucleotide analogues and methods utilizing the same
  申请人：Kaneko Masakatsu

  公开号：US20090149404A1

  公开（公告）日：2009-06-11

  A method for the prevention or treatment in a mammal of a disease preventable or treatable by the pharmacologically useful antisense or antigene activity of an oligonucleotide analogue or a pharmacologically acceptable salt thereof in the body of said mammal, which method comprises administering to said mammal in need of such prevention or treatment a pharmaceutically effective amount of an oligonucleotide analogue comprising two or more nucleoside units, wherein at least one of said nucleoside units is a structure of the formula (2): wherein A is methylene; and B is an unsubstituted purin-9-yl, an unsubstituted 2-oxo-pyrimidin-1-yl or a substituted purin-9-yl; or a pharmacologically acceptable salt thereof.
• US7314923B2
  申请人：——

  公开号：US7314923B2

  公开（公告）日：2008-01-01