(3S,3aR)-1-chloro-3-methyl-3-phenyltetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaphosphole | 1133388-15-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3S,3aR)-1-chloro-3-methyl-3-phenyltetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaphosphole
• 英文别名: (3S,3aR)-1-chloro-3-methyl-3-phenyl-3a,4,5,6-tetrahydropyrrolo[1,2-c][1,3,2]oxazaphosphole
• CAS: 1133388-15-4
• 化学式: C₁₂H₁₅ClNOP
• 分子量: 255.684
• InChiKey: RHCJVEFZZDCPLG-WWMUWCCSSA-N

物化性质

• 沸点：
  323.4±45.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3S,3aR)-1-chloro-3-methyl-3-phenyltetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaphosphole 、 5'-O-N⁶-di-(4,4'-dimethoxytrityl)-2'-deoxyadenosine 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以80%的产率得到
  参考文献：
  名称：

  使用酸不稳定的N-保护基团通过氧杂氮杂吡啶方法立体控制合成寡聚脱氧核糖核苷硼酸磷酸酯

  摘要：

  使用非对映体2'-脱氧核糖核苷3'- O-氧杂氮杂膦酸单体，通过在核碱基上带有酸不稳定保护基的非对映异构体2'-脱氧核糖核苷3'- O-氧杂氮杂磷酰胺单体，以立体控制的方式，通过具有完全脱保护的核碱基的相应H-膦酸酯，以立体控制的方式合成了寡脱氧核糖核苷硼酸磷酸酯（PB-ODN）。使用所得的立体定义的PB-ODN，我们证明了PB-ODN与互补寡核苷酸的双链体的热稳定性取决于其磷原子的构型。

  DOI：

  10.1016/j.tetlet.2012.06.015

文献信息

• Stereocontrolled Solid-Phase Synthesis of Oligonucleoside<i>H</i>-Phosphonates by an Oxazaphospholidine Approach
  作者：Naoki Iwamoto、Natsuhisa Oka、Terutoshi Sato、Takeshi Wada

  DOI：10.1002/anie.200804408

  日期：2009.1.5

  Stereodefined oligonucleoside H‐phosphonates were synthesized on a solid support using diastereopure nucleoside 3′‐O‐oxazaphospholidine monomers. Several stereodefined backbone‐modified analogues were obtained with the oligonucleoside H‐phosphonates as precursors (see scheme; BPRO=protected nucleobase, DMTr=4,4′‐dimethoxytrityl, Th=thymin‐1‐yl, TfO−=triflate).

  使用非对映体纯核苷3'- O-氧杂氮杂磷啶单体在固体支持物上合成立体定义的寡核苷H-膦酸酯。与寡核苷得到几个stereodefined骨架修饰的类似物ħ -phosphonates作为前体（参见方案;乙PRO =保护的核碱基，将DMTr = 4,4'-二甲氧基三苯甲基，TH =胸腺嘧啶-1-基，TFO - =三氟甲磺酸酯）。
• Enhancement of the affinity of 2′-O-Me-oligonucleotides for complementary RNA by incorporating a stereoregulated boranophosphate backbone
  作者：Yohei Nukaga、Tetsuhiko Takemura、Naoki Iwamoto、Natsuhisa Oka、Takeshi Wada

  DOI：10.1039/c4ra11335g

  日期：——

  P-stereodefined boranophosphate 2′-O-Me-oligoribonucleotides (2′-O-Me-PB-ORNs) were synthesized and we revealed that an all-(Sp)-PB-backbone largely stabilized the duplex with RNA.

  合成了P-立体定义的硼酸酯2'-O-甲基寡核苷酸（2'-O-Me-PB-ORNs），我们揭示了全（Sp）-PB-骨架大大稳定了与RNA形成的双链结构。
• CHIRAL CONTROL
  申请人：WAVE LIFE SCIENCES PTE. LTD.

  公开号：US20150211006A1

  公开（公告）日：2015-07-30

  The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

  本发明涉及手性控制的寡核苷酸、手性控制的寡核苷酸组合物以及其制备和使用方法。本发明特别涵盖了鉴定以前制备手性寡核苷酸方法中某些问题的来源，包括禁止制备完全手性控制的组合物，特别是包含多种寡核苷酸类型的组合物。在某些实施例中，本发明提供了手性控制的寡核苷酸组合物。在某些实施例中，本发明提供了制备手性控制的寡核苷酸和手性控制的寡核苷酸组合物的方法。
• Oligonucleotide compositions and methods thereof
  申请人：WAVE LIFE SCIENCES LTD.

  公开号：US10450568B2

  公开（公告）日：2019-10-22

  Among other things, the present disclosure relates to designed oligonucleotides, compositions, and methods thereof. In some embodiments, provided oligonucleotide compositions provide altered splicing of a transcript. In some embodiments, provided oligonucleotide compositions have low toxicity. In some embodiments, provided oligonucleotide compositions provide improved protein binding profiles. In some embodiments, provided oligonucleotide compositions have improved delivery. In some embodiments, provided oligonucleotide compositions have improved uptake. In some embodiments, the present disclosure provides methods for treatment of diseases using provided oligonucleotide compositions.

  除其他外，本公开涉及设计的寡核苷酸、组合物及其方法。在一些实施方案中，所提供的寡核苷酸组合物能改变转录本的剪接。在一些实施方案中，所提供的寡核苷酸组合物具有低毒性。在一些实施方案中，所提供的寡核苷酸组合物提供了改进的蛋白质结合概况。在一些实施方案中，所提供的寡核苷酸组合物具有更好的传递性。在一些实施方案中，所提供的寡核苷酸组合物改善了吸收。在一些实施方案中，本公开提供了使用所提供的寡核苷酸组合物治疗疾病的方法。
• Chiral control
  申请人：WAVE LIFE SCIENCES LTD.

  公开号：US10590413B2

  公开（公告）日：2020-03-17

  The present invention relates to chirally controlled oligonucleotides, chirally controlled oligonucleotide compositions, and the method of making and using the same. The invention specifically encompasses the identification of the source of certain problems with prior methodologies for preparing chiral oligonucleotides, including problems that prohibit preparation of fully chirally controlled compositions, particularly compositions comprising a plurality of oligonucleotide types. In some embodiments, the present invention provides chirally controlled oligonucleotide compositions. In some embodiments, the present invention provides methods of making chirally controlled oligonucleotides and chirally controlled oligonucleotide compositions.

  本发明涉及手性受控寡核苷酸、手性受控寡核苷酸组合物以及制作和使用方法。本发明具体包括确定先前制备手性寡核苷酸方法中某些问题的根源，包括禁止制备完全手性控制的组合物，特别是包含多种寡核苷酸类型的组合物的问题。在某些实施方案中，本发明提供了手性控制的寡核苷酸组合物。在一些实施方案中，本发明提供了制作手性控制寡核苷酸和手性控制寡核苷酸组合物的方法。