3,6-anhydro-1,2-dideoxy-1-(trimethylsilyl)-4,5,7-tri-O-benzoyl-D-allo-hept-1-ynitol | 1142010-55-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,6-anhydro-1,2-dideoxy-1-(trimethylsilyl)-4,5,7-tri-O-benzoyl-D-allo-hept-1-ynitol
• 英文别名: [(2R,3R,4S,5S)-3,4-dibenzoyloxy-5-(2-trimethylsilylethynyl)oxolan-2-yl]methyl benzoate
• CAS: 1142010-55-6
• 化学式: C₃₁H₃₀O₇Si
• 分子量: 542.66
• InChiKey: QUTRMHYGSIGDSK-ZVBOOHQUSA-N

物化性质

• 沸点：
  616.2±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.94
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3,6-anhydro-1,2-dideoxy-1-(trimethylsilyl)-4,5,7-tri-O-benzoyl-D-allo-hept-1-ynitol 在 ammonium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 1-deoxy-1-ethynyl-β-D-ribofuranose
  参考文献：
  名称：

  Short Interfering RNA Guide Strand Modifiers from Computational Screening

  摘要：

  Short interfering RNAs (siRNAs) are promising drug candidates for a wide range of targets including those previously considered "undruggable. However, properties associated with the native RNA structure limit drug development, and chemical modifications are necessary. Here we describe the structure-guided discovery of functional modifications for the guide strand 5'-end using computational screening with the high-resolution structure of human Ago2, the key nuclease on the RNA interference pathway. Our results indicate the guide strand 5'-end nucleotide need not engage in Watson-Crick (W/C) H-bonding but must fit the general shape of the 5'-end binding site in MID/PIWI domains of hAgo2 for efficient knockdown. 1,2,3-Triazol-4-yl bases formed from the CuAAC reaction of azides and 1-ethynylribose, which is readily incorporated into RNA via the phosphoramidite, perform well at the guide strand 5'-end. In contrast, purine derivatives with modified Hoogsteen faces or N2 substituents are poor choices for 5'-end modifications. Finally, we identified a 1,2,3-triazol-4-yl base incapable of W/C H-bonding that performs well at guide strand position 12, where base pairing to target was expected to be important. This work expands the repertoire of functional nucleotide analogues for siRNAs.

  DOI：

  10.1021/ja4079754
• 作为产物：
  描述：

  三甲基乙炔基硅 在 正丁基锂 作用下， 以 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.5h， 生成 3,6-anhydro-1,2-dideoxy-1-(trimethylsilyl)-4,5,7-tri-O-benzoyl-D-allo-hept-1-ynitol
  参考文献：
  名称：

  Short Interfering RNA Guide Strand Modifiers from Computational Screening

  摘要：

  Short interfering RNAs (siRNAs) are promising drug candidates for a wide range of targets including those previously considered "undruggable. However, properties associated with the native RNA structure limit drug development, and chemical modifications are necessary. Here we describe the structure-guided discovery of functional modifications for the guide strand 5'-end using computational screening with the high-resolution structure of human Ago2, the key nuclease on the RNA interference pathway. Our results indicate the guide strand 5'-end nucleotide need not engage in Watson-Crick (W/C) H-bonding but must fit the general shape of the 5'-end binding site in MID/PIWI domains of hAgo2 for efficient knockdown. 1,2,3-Triazol-4-yl bases formed from the CuAAC reaction of azides and 1-ethynylribose, which is readily incorporated into RNA via the phosphoramidite, perform well at the guide strand 5'-end. In contrast, purine derivatives with modified Hoogsteen faces or N2 substituents are poor choices for 5'-end modifications. Finally, we identified a 1,2,3-triazol-4-yl base incapable of W/C H-bonding that performs well at guide strand position 12, where base pairing to target was expected to be important. This work expands the repertoire of functional nucleotide analogues for siRNAs.

  DOI：

  10.1021/ja4079754

文献信息

• [EN] CYCLIC DINUCLEOTIDES AS ANTICANCER AGENTS<br/>[FR] DINUCLÉOTIDES CYCLIQUES UTILISÉS EN TANT QU'AGENTS ANTICANCÉREUX
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2019079261A1

  公开（公告）日：2019-04-25

  The present invention is directed to compounds of the formula (I) wherein all substituents are defined herein, as well as pharmaceutically acceptable compositions comprising compounds of the invention and methods of using said compositions in the treatment of various disorders.

  本发明涉及式(I)的化合物，其中所有取代基在此定义，以及包括该发明化合物的药学上可接受的组合物，以及使用该组合物治疗各种疾病的方法。
• One-pot multicomponent synthesis of 2,3-dihydropyrans: new access to furanose–pyranose 1,3-C–C-linked-disaccharides
  作者：Daniele Castagnolo、Lorenzo Botta、Maurizio Botta

  DOI：10.1016/j.tetlet.2009.01.047

  日期：2009.4

  An efficent synthesis of 2,3-dihydropyrans from different terminal alkynes was developed. The 2,3-dihydropyrans were obtained in a few minutes through a microwave-assisted multicomponent enyne cross-metathesis/hetero-Diels-Alder reaction. Starting from C-ethynyl-ribofuranose, a new multicomponent approach to furanose-pyramose 1,3-C-C-linked disaccharides was also developed. (C) 2009 Elsevier Ltd. All rights reserved.
• Short Interfering RNA Guide Strand Modifiers from Computational Screening
  作者：Kazumitsu Onizuka、Jason G. Harrison、Alexi A. Ball-Jones、José M. Ibarra-Soza、Yuxuan Zheng、Diana Ly、Walter Lam、Stephanie Mac、Dean J. Tantillo、Peter A. Beal

  DOI：10.1021/ja4079754

  日期：2013.11.13

  Short interfering RNAs (siRNAs) are promising drug candidates for a wide range of targets including those previously considered "undruggable. However, properties associated with the native RNA structure limit drug development, and chemical modifications are necessary. Here we describe the structure-guided discovery of functional modifications for the guide strand 5'-end using computational screening with the high-resolution structure of human Ago2, the key nuclease on the RNA interference pathway. Our results indicate the guide strand 5'-end nucleotide need not engage in Watson-Crick (W/C) H-bonding but must fit the general shape of the 5'-end binding site in MID/PIWI domains of hAgo2 for efficient knockdown. 1,2,3-Triazol-4-yl bases formed from the CuAAC reaction of azides and 1-ethynylribose, which is readily incorporated into RNA via the phosphoramidite, perform well at the guide strand 5'-end. In contrast, purine derivatives with modified Hoogsteen faces or N2 substituents are poor choices for 5'-end modifications. Finally, we identified a 1,2,3-triazol-4-yl base incapable of W/C H-bonding that performs well at guide strand position 12, where base pairing to target was expected to be important. This work expands the repertoire of functional nucleotide analogues for siRNAs.