3,5-di-O-benzyl-4-C-(tert-butyldiphenylsilyloxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose

• 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: 3,5-di-O-benzyl-4-C-(tert-butyldiphenylsilyloxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose
• 英文别名: [(3aR,5S,6S,6aR)-2,2-dimethyl-6-phenylmethoxy-5-(phenylmethoxymethyl)-6,6a-dihydro-3aH-furo[2,3-d][1,3]dioxol-5-yl]methoxy-tert-butyl-diphenylsilane
• 化学式: C₃₉H₄₆O₆Si
• 分子量: 638.876
• InChiKey: HIPAJCKXJLUJOR-WSTRYJQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.61
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3,5-di-O-benzyl-4-C-(tert-butyldiphenylsilyloxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose 在 吡啶 、 4-二甲氨基吡啶 、 重铬酸吡啶 、 N,O-双三甲硅基乙酰胺 、 三氟甲烷磺酰氯 、 三氟甲磺酸三甲基硅酯 、 硫酸 、 水 、 一水合肼 、 溶剂黄146 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 triethylamine tris(hydrogen fluoride) 、 甲胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 68.34h， 生成 3',5'-di-O-benzyl-4'-carboxy-2'-O-(N-methyleneamino)-5-methyluridine
  参考文献：
  名称：

  BRIDGED ARTIFICIAL NUCLEOSIDE AND NUCLEOTIDE

  摘要：

  本发明的目的是提供一种新型分子用于反义疗法，该分子在体内不易受核酸酶降解，并且对目标mRNA具有高结合亲和力和特异性，能够有效调节特定基因的表达。本发明的新型人工核苷酸在2′,4′-BNA/LNA的桥接结构中引入了酰胺键。含有2′,4′-桥接人工核苷酸的寡核苷酸与已知的2′,4′-BNA/LNA具有相当的单链RNA结合亲和力，并且比LNA具有更高的核酸酶抗性。特别地，由于其比S-oligo对单链RNA的结合亲和力更强，预计将被应用于核酸药物。

  公开号：

  US20120208991A1
• 作为产物：
  描述：

  3-O-benzyl-1,2-O-isopropylidene-α-D-allofuranose 在 咪唑 、 sodium periodate 、 sodium hydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 56.5h， 生成 3,5-di-O-benzyl-4-C-(tert-butyldiphenylsilyloxymethyl)-1,2-O-isopropylidene-α-D-ribofuranose
  参考文献：
  名称：

  糖和核苷类似物的合成及其抗癌和镇痛潜力的评价

  摘要：

  糖和核苷的化学修饰在生产具有更高选择性和功效的化合物方面有着悠久的历史。在这项研究中，由 α- d-葡萄糖通过总共 21 个步骤合成了几种修饰糖 (2-3 )和核糖核苷类似物 ( 4-8 ) 。在乙酸诱导的小鼠扭体试验中测试了化合物的外周抗伤害特性，其中化合物2、7和8显示扭伤次数分别显着减少了 56%、62% 和 63%。还通过台盼蓝染料排除试验和细胞计数试剂盒 8 (CCK-8) 测定法测试了这些化合物对人 HeLa 细胞系的细胞毒性潜力。化合物6表现出显着的细胞毒活性，IC 50值为 54 µg/mL。分子对接模拟显示化合物2、7和8对环氧合酶 1 ( COX-1) 和环氧合酶 2 (COX-2) 酶具有相当的结合亲和力。此外，桥接核苷类似物7和8也有效抑制腺苷激酶，这表明其抗伤害作用背后的替代机制途径。细胞毒性化合物6与抗癌药物靶点人胞苷脱氨酶、原癌基因酪氨酸蛋白激酶 Src、人胸苷激酶

  DOI：

  10.3390/molecules27113499

文献信息

• BRIDGED ARTIFICIAL NUCLEOSIDE AND NUCLEOTIDE
  申请人：Obika Satoshi

  公开号：US20120208991A1

  公开（公告）日：2012-08-16

  It is an object of the present invention to provide a novel molecule for antisense therapies which is not susceptible to nuclease degradation in vivo and has a high binding affinity and specificity for the target mRNAs and which can efficiently regulate expression of specific genes. The novel artificial nucleoside of the present invention has an amide bond introduced into a bridge structure of 2′,4′-BNA/LNA. The oligonucleotide containing the 2′,4′-bridged artificial nucleotide has a binding affinity for a single-stranded RNA comparable to known 2′,4′-BNA/LNA and has an increased nuclease resistance over LNA. Particularly, it is expected to be applied to nucleic acid drugs because of its much stronger binding affinity for single-stranded RNAs than S-oligo's affinity

  本发明的目的是提供一种新型分子用于反义疗法，该分子在体内不易受核酸酶降解，并且对目标mRNA具有高结合亲和力和特异性，能够有效调节特定基因的表达。本发明的新型人工核苷酸在2′,4′-BNA/LNA的桥接结构中引入了酰胺键。含有2′,4′-桥接人工核苷酸的寡核苷酸与已知的2′,4′-BNA/LNA具有相当的单链RNA结合亲和力，并且比LNA具有更高的核酸酶抗性。特别地，由于其比S-oligo对单链RNA的结合亲和力更强，预计将被应用于核酸药物。
• 修饰核苷、核苷酸和核酸聚合物及其制备方法 与应用
  申请人：中国人民解放军军事科学院军事医学研究院

  公开号：CN110590886B

  公开（公告）日：2021-03-23

  本发明涉及修饰核苷、核苷酸和核酸聚合物及其制备方法与应用。所述修饰核苷选自具有如式(I)所示结构的化合物、其盐或其异构体；其中，R1选自取代或未取代的碱基或其盐；X代表O或S；R2选自氢或者取代或未取代的：C1～C6烷基、C1～C6杂烷基、C2～C6烯基、C2～C6炔基、芳基或杂芳基；R3和R4独立地选自氢或者取代或未取代的：C1～C6烷基、C1～C6杂烷基；W1和W2独立地选自H或保护基团。所述修饰核苷在6’位引入了腈基，并在此基础上进一步获得修饰核苷酸和核酸聚合物，极大地改善了它们的核酶耐受性，对靶RNA具有高度选择性和较强结合亲和力。
• Conformationally constrained analogues of diacylglycerol (DAG). Part 19: Asymmetric syntheses of (3R)- and (3S)-3-hydroxy-4,4-disubstituted heptono-1,4-lactones as protein kinase C (PK-C) ligands with increased hydrophilicity
  作者：Kassoum Nacro、Jeewoo Lee、Joseph J Barchi、Nancy E Lewin、Peter M Blumberg、Victor E Marquez

  DOI：10.1016/s0040-4020(02)00477-5

  日期：2002.6

  The stereospecific introduction of (R)- and (S)-OH groups at position C-3 of two diacylglycerol gamma-lactones (DAG-lactones) previously identified as strong protein kinase C (PK-C) ligands is presented. The compounds were designed to investigate whether the extra OH group in a specific orientation could establish an additional hydrogen bond with the C1 domain of PK-C, thus providing a DAG analogue with reduced lipophilicity. The OH groups were introduced following two different diastereoselective multistep syntheses starting from diacetone-D-glucose. The PK-C binding affinities for the new compounds were weaker in comparison to those of the parent compounds, suggesting that the extra OH does not engage efficiently in hydrogen bonding at the receptor. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Synthesis and Properties of a Bridged Nucleic Acid with a Perhydro-1,2-oxazin-3-one Ring
  作者：Ajaya R. Shrestha、Yoshiyuki Hari、Aiko Yahara、Takashi Osawa、Satoshi Obika

  DOI：10.1021/jo201597e

  日期：2011.12.16

  A novel derivative of 2',4'-bridged nucleic acid, named hydroxamate-bridged nucleic acid (HxNA), containing a six-membered perhydro-1,2-oxazin-3-one ring, was designed and synthesized. The introduction of a carbonyl function along with an N-O linkage in the six-membered bridged structure is the unique structural feature of the novel 2',4'-bridged nucleic acid analogue. The design was carried out to restrict the flexibility of the sugar moiety through the trigonal planarity of carbonyl function, which would improve the properties of the modification. The synthesized monomer was incorporated into oligonucleotides, and their properties were examined. The HxNA-modified oligonucleotides exhibited selectively high affinity toward complementary ssRNA. Furthermore, the nuclease resistance of the HxNA-modified oligonucleotide was found to be higher than that of the corresponding natural and 2',4'-BNA/LNA-modified oligonucleotides. Interestingly, exposure of HxNA modified oligonucleotide to 3'-exonuclease resulted in gradual opening of the bridge, which stopped further digestion. Moreover, ring-opening of only one modification at the 3'-end of the oligonucleotides was observed, even if two or three HxNA modifications were present in the sequence. The results demonstrate the strong potential of the HxNA modification as a switch for the generation of highly nuclease-resistant RNA selective oligonucleotide in situ, which could have potential applications in antisense technology.
• Synthesis of Sugar and Nucleoside Analogs and Evaluation of Their Anticancer and Analgesic Potentials
  作者：Fahad Hussain、Fahad Imtiaz Rahman、Poushali Saha、Atsushi Mikami、Takashi Osawa、Satoshi Obika、S. M. Abdur Rahman

  DOI：10.3390/molecules27113499

  日期：——

  Molecular docking simulations revealed that compounds 2, 7, and 8 had a comparable binding affinity to cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. Additionally, the bridged nucleoside analogs 7 and 8 potently inhibited adenosine kinase enzyme as well, which indicates an alternate mechanistic pathway behind their anti-nociceptive action. Cytotoxic compound 6 demonstrated strong docking

  糖和核苷的化学修饰在生产具有更高选择性和功效的化合物方面有着悠久的历史。在这项研究中，由 α- d-葡萄糖通过总共 21 个步骤合成了几种修饰糖 (2-3 )和核糖核苷类似物 ( 4-8 ) 。在乙酸诱导的小鼠扭体试验中测试了化合物的外周抗伤害特性，其中化合物2、7和8显示扭伤次数分别显着减少了 56%、62% 和 63%。还通过台盼蓝染料排除试验和细胞计数试剂盒 8 (CCK-8) 测定法测试了这些化合物对人 HeLa 细胞系的细胞毒性潜力。化合物6表现出显着的细胞毒活性，IC 50值为 54 µg/mL。分子对接模拟显示化合物2、7和8对环氧合酶 1 ( COX-1) 和环氧合酶 2 (COX-2) 酶具有相当的结合亲和力。此外，桥接核苷类似物7和8也有效抑制腺苷激酶，这表明其抗伤害作用背后的替代机制途径。细胞毒性化合物6与抗癌药物靶点人胞苷脱氨酶、原癌基因酪氨酸蛋白激酶 Src、人胸苷激酶