1-(1,3-anhydro-β-D-psicofuranosyl)cytosine | 53263-38-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧环庚烷
• 英文名称: 1-(1,3-anhydro-β-D-psicofuranosyl)cytosine
• 英文别名: 1-(1',3'-O-anhydro-β-D-psicofuranosyl)cytosine；1-(1,3-Anhydro-β-D-psicofuranosyl)cytosin；4-amino-1-(β-D-1,3-anhydro-psicofuranosyl)-1H-pyrimidin-2-one；4-amino-1-[(1R,3R,4R,5R)-4-hydroxy-3-(hydroxymethyl)-2,6-dioxabicyclo[3.2.0]heptan-1-yl]pyrimidin-2-one
• CAS: 53263-38-0
• 化学式: C₁₀H₁₃N₃O₅
• 分子量: 255.23
• InChiKey: BEZUAMSJTJZOQS-VPCXQMTMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  118
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(1,3-anhydro-β-D-psicofuranosyl)cytosine 在 吡啶 、 4-二甲氨基吡啶 、 三甲基氯硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 19.5h， 生成 Succinic acid mono-[(1R,3R,4R,5R)-3-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-1-(4-isobutylamino-2-oxo-2H-pyrimidin-1-yl)-2,6-dioxa-bicyclo[3.2.0]hept-4-yl] ester
  参考文献：
  名称：

  Antisense oligonuclotides with oxetane-constrained cytidine enhance heteroduplex stability, and elicit satisfactory RNase H response as well as showing improved resistance to both exo and endonucleasesElectronic supplementary information (ESI) available: RNA cleavage kinetics. See http://www.rsc.org/suppdata/ob/b2/b210163g/

  摘要：

  与相应的-修饰的反义寡核苷酸[1′,2′-氧杂环丁烷约束胞苷、1-(1′,3′-O-脱水-β-D-二十呋喃糖基)胞嘧啶]相比，我们通过靶向 15 聚体互补 RNA 评估了它们的反义潜力。虽然修饰的混合 AONs 每修饰一次，其混合 AON-RNA 双链体的熔点（Tm）就会下降 3 ℃，但与原生 AON-RNA 双链体相比，它们是 RNase H 的良好底物。经过双重修饰和 3′-DPPZ（二哒嗪）共轭的 AON 显示，混合双链体的 Tm 与原生双链体一样高，而 RNase H 的活性与其未共轭的对应物一样好。RNase H裂解的详细迈克尔斯-门顿动力学分析表明，单修饰和双修饰的AON-RNA双链体以及与3′-DPPZ一起双修饰的AON-RNA双链体的催化活性（kcat）接近原生双链体。然而，RNase H的结合亲和力（1/Km）随着修饰数目的增加而略有下降，这导致修饰的AON-RNA双链体的有效酶活性（kcat/Km）降低。所有经过氧杂环丁烷修饰的 AON-RNA 杂交体都显示出 Tm 与 1/Km、Vmax 或 Vmax/Km 的相关性。与原生AON相比，改性AON（含3′-DPPZ）对内切酶和外切酶降解的耐受性更强（基于氧杂环丁烷-糖和DPPZ的AON对K562细胞生长无毒，参考文献）。因此，在外切酶和内切酶的稳定性与异质双链的热稳定性、RNase H 的招募能力和裂解能力之间找到了平衡点，以氧杂环丁烷约束的胞苷结合 AONs 作为具有完全磷酸骨架的潜在反义候选物，可用于进一步的生物学评估。

  DOI：

  10.1039/b210163g
• 作为产物：
  描述：

  4-Amino-1-((1R,3R,4R,5R)-4-benzyloxy-3-hydroxymethyl-2,6-dioxa-bicyclo[3.2.0]hept-1-yl)-1H-pyrimidin-2-one 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 24.0h， 以62%的产率得到1-(1,3-anhydro-β-D-psicofuranosyl)cytosine
  参考文献：
  名称：

  嘧啶 1',3'-脱水-β-d-psico-和-山梨-呋喃糖基核苷的合成

  摘要：

  已经开发了一种分别合成嘧啶 1',3'-脱水-β-D-psico-和-山梨-呋喃糖基核苷 2 和 3 的新方法。此处描述的方法采用易于获得的 O 2 ,3'-脱水-β-D-呋喃果糖尿嘧啶 (1) 作为关键起始化合物。

  DOI：

  10.1055/s-2005-871547

文献信息

• Antisense oligonuclotides with oxetane-constrained cytidine enhance heteroduplex stability, and elicit satisfactory RNase H response as well as showing improved resistance to both exo and endonucleasesElectronic supplementary information (ESI) available: RNA cleavage kinetics. See http://www.rsc.org/suppdata/ob/b2/b210163g/
  作者：Pushpangadan. I. Pradeepkumar、Nariman V. Amirkhanov、Jyoti Chattopadhyaya

  DOI：10.1039/b210163g

  日期：2003.12.19

  Antisense oligonucleotides (AONs) with single and double oxetane modifications [1′,2′-oxetane constrained cytidine, 1-(1′,3′-O-anhydro-β-D-psicofuranosyl)cytosine] have been evaluated, in comparison with the corresponding -modified AONs, for their antisense potentials by targeting to a 15mer complementary RNA. Although the modified mixmer AONs show ∼3 °C drop per modification in melting temperature (Tm) of their hybrid AON–RNA duplexes, they are found to be good substrates for RNase H, in comparison with the native AON–RNA duplex. An AON with double modifications along with 3′-DPPZ (dipyridophenazine) conjugation shows the Tm of the hybrid duplexes as high as that of the native, and the RNase H activity as good as its unconjugated counterpart. A detailed Michaelis–Menten kinetic analysis of RNase H cleavage showed that the single and double modified AON–RNA duplexes as well as double modifications along with 3′-DPPZ have catalytic activities (kcat) close to the native. However, the RNase H binding affinity (1/Km) showed a slight decrease with increase in the number of modifications, which results in less effective enzyme activity (kcat/Km) for modified AON–RNA duplexes. All oxetane modified AON–RNA hybrids showed a correlation of Tm with the 1/Km, Vmax, or Vmax/Km. The modified AONs (with 3′-DPPZ), as in the counterpart, showed an enhanced tolerance towards the endonuclease and exonuclease degradation compared to the native (the oxetane-sugar and the DPPZ based AONs are non-toxic to K562 cell growth, ref. ). Thus a balance has been found between exo and endonuclease stability vis-a-vis thermostability of the heteroduplex and the RNase H recruitment capability and cleavage with the oxetane-constrained cytidine incorporated AONs as potential antisense candidates with a fully phosphate backbone for further biological assessment.

  与相应的-修饰的反义寡核苷酸[1′,2′-氧杂环丁烷约束胞苷、1-(1′,3′-O-脱水-β-D-二十呋喃糖基)胞嘧啶]相比，我们通过靶向 15 聚体互补 RNA 评估了它们的反义潜力。虽然修饰的混合 AONs 每修饰一次，其混合 AON-RNA 双链体的熔点（Tm）就会下降 3 ℃，但与原生 AON-RNA 双链体相比，它们是 RNase H 的良好底物。经过双重修饰和 3′-DPPZ（二哒嗪）共轭的 AON 显示，混合双链体的 Tm 与原生双链体一样高，而 RNase H 的活性与其未共轭的对应物一样好。RNase H裂解的详细迈克尔斯-门顿动力学分析表明，单修饰和双修饰的AON-RNA双链体以及与3′-DPPZ一起双修饰的AON-RNA双链体的催化活性（kcat）接近原生双链体。然而，RNase H的结合亲和力（1/Km）随着修饰数目的增加而略有下降，这导致修饰的AON-RNA双链体的有效酶活性（kcat/Km）降低。所有经过氧杂环丁烷修饰的 AON-RNA 杂交体都显示出 Tm 与 1/Km、Vmax 或 Vmax/Km 的相关性。与原生AON相比，改性AON（含3′-DPPZ）对内切酶和外切酶降解的耐受性更强（基于氧杂环丁烷-糖和DPPZ的AON对K562细胞生长无毒，参考文献）。因此，在外切酶和内切酶的稳定性与异质双链的热稳定性、RNase H 的招募能力和裂解能力之间找到了平衡点，以氧杂环丁烷约束的胞苷结合 AONs 作为具有完全磷酸骨架的潜在反义候选物，可用于进一步的生物学评估。
• Synthesis of Pyrimidine 1′,3′-Anhydro-β-<scp>d</scp>-<i>psico</i>- and -<i>sorbo</i>-furanosyl Nucleosides
  作者：Igor A. Mikhailopulo、Tamara I. Kulak、Olga V. Tkachenko、Svetlana L. Sentjureva、Jouko Vepsäläinen

  DOI：10.1055/s-2005-871547

  日期：——

  A novel approach for the synthesis of pyrimidine 1',3'-anhydro-β-D-psico- and -sorbo-furanosyl nucleosides 2 and 3, respectively, has been developed. The approach described here employs a readily available O 2 ,3'-anhydro-β-D-fructofuranosyluracil (1) as a key starting compound.

  已经开发了一种分别合成嘧啶 1',3'-脱水-β-D-psico-和-山梨-呋喃糖基核苷 2 和 3 的新方法。此处描述的方法采用易于获得的 O 2 ,3'-脱水-β-D-呋喃果糖尿嘧啶 (1) 作为关键起始化合物。