1-{2,6-anhydro-3-O-benzyl-4-[(benzyloxy)methyl]-5-deoxy-α-L-lyxo-hexofuranosyl}-5-methylpyrimidine-2,4(1H,3H)-dione | 287737-37-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-{2,6-anhydro-3-O-benzyl-4-[(benzyloxy)methyl]-5-deoxy-α-L-lyxo-hexofuranosyl}-5-methylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 3',5'-di-O-benzyl-2'-O,4'-C-ethylene-5-methyluridine；5-methyl-1-[(1R,5R,7R,8S)-8-phenylmethoxy-5-(phenylmethoxymethyl)-2,6-dioxabicyclo[3.2.1]octan-7-yl]pyrimidine-2,4-dione
• CAS: 287737-37-5
• 化学式: C₂₆H₂₈N₂O₆
• 分子量: 464.518
• InChiKey: WDKFHIWXFSIVPK-MWXBQQNOSA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  86.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-{2,6-anhydro-3-O-benzyl-4-[(benzyloxy)methyl]-5-deoxy-α-L-lyxo-hexofuranosyl}-5-methylpyrimidine-2,4(1H,3H)-dione 在 palladium dihydroxide 吡啶 、 氢气 作用下， 以 甲醇 为溶剂， 反应 10.0h， 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 吡啶 、 sodium hydroxide 、 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 1-{2,6-anhydro-3-O-benzyl-4-[(benzyloxy)methyl]-5-deoxy-α-L-lyxo-hexofuranosyl}-5-methylpyrimidine-2,4(1H,3H)-dione
  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

• An improved synthesis of 2′-<i>O</i>,4′-<i>C</i>-ethylene nucleic acid (ENA) and thermodynamic studies of duplex formation containing the guanosine ENA unit
  作者：Miho Takagi-Sato、Koji Morita、Yoshiyuki Onishi、Yuuka Watahiki、Taku Ishigaki、Tomoka Akita、Erisa Tomita、Junji Kawakami、Makoto Koizumi

  DOI：10.1080/15257770.2019.1708389

  日期：2020.6.2

  substrate, we developed several methods to obtain 2′-O,4′-C-ethyleneguanosine derivatives with much higher yields than previously reported. These methods were also applicable for the synthesis of 2′-O,4′-C-ethyleneadenosine and 2′-O,4′-C-ethylene-5-methyluridine derivatives. Moreover, we investigated the thermodynamic benefit of DNA strands containing 2′-O,4′-C-ethyleneguanosines during duplex formation

  摘要 含有 2'-O,4'-C-乙烯核酸 (ENA) 的寡核苷酸已被证明对反义治疗非常有效。2'-O,4'-C-亚乙基鸟苷及其亚磷酰胺先前是从 3,5-di-O-benzy1-4-C-(p-tollulenesulfonyloxyethyl)-1,2-di-O-acetyl-α- D-呋喃戊糖通过糖基化，但效率有限。使用 3,5-di-O-benzy1-4-C-(2-t-butyldiphenylsilyloxyethyl)-1,2-di-O-acetyl-α-D-erythropentofuranose 作为替代底物，我们开发了几种方法来获得 2 '-O,4'-C-亚乙基鸟苷衍生物的产率比以前报道的高得多。这些方法也适用于合成 2'-O,4'-C-亚乙基腺苷和 2'-O,4'-C-乙烯-5-甲基尿苷衍生物。此外，我们研究了含有 2'-O 的 DNA 链的热力学益处，与互补 RNA 形成双链体期间的
• Synthesis and properties of 2′-O,4′-C-Ethylene-Bridged nucleic acids (ENA) as effective antisense oligonucleotides
  作者：Koji Morita、Miho Takagi、Chikako Hasegawa、Masakatsu Kaneko、Shinya Tsutsumi、Junko Sone、Tomio Ishikawa、Takeshi Imanishi、Makoto Koizumi

  DOI：10.1016/s0968-0896(03)00115-9

  日期：2003.5

  bridged nucleic acids (2',4'-BNA) or locked nucleic acids (LNA). Both the 2'-O,4'-C-ethylene- and propylene-linkage within these nucleosides restrict the sugar puckering to the N-conformation of RNA as do 2',4'-BNA/LNA. Furthermore, ethylene-bridged nucleic acids (ENA) having 2'-O,4'-C-ethylene nucleosides had considerably increased the affinity to complementary RNA, and were as high as that of 2',4'-BNA/LNA

  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
• 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
• INTERMEDIATE FOR PRODUCTION OF NUCLEOSIDE ANALOGUE, AND METHOD FOR PRODUCING SAME
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP2862868B1

  公开（公告）日：2020-04-08
• NOVEL NUCLEOSIDES AND OLIGONUCLEOTIDE ANALOGUES
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP1152009B2

  公开（公告）日：2017-09-06