3',5'-di-O-acetyl-5-iodo-4-thio-2'-deoxyuridine | 384338-45-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 3',5'-di-O-acetyl-5-iodo-4-thio-2'-deoxyuridine
• 英文别名: [(2R,3S,5R)-3-acetyloxy-5-(5-iodo-2-oxo-4-sulfanylidenepyrimidin-1-yl)oxolan-2-yl]methyl acetate
• CAS: 384338-45-8
• 化学式: C₁₃H₁₅IN₂O₆S
• 分子量: 454.242
• InChiKey: BXUPATKBYVHUER-HBNTYKKESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3',5'-di-O-acetyl-5-iodo-4-thio-2'-deoxyuridine 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 TEA 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 [(2R,3S,5R)-3-acetyloxy-5-(4-methylsulfanyl-2-oxo-5-undec-1-ynylpyrimidin-1-yl)oxolan-2-yl]methyl acetate
  参考文献：
  名称：

  Bicyclic anti-VZV nucleosides: Thieno analogues retain full antiviral activity

  摘要：

  Thieno analogues of the potent and selective furo-pyrimidine anti-VZV nucleoside family are herein reported. The compounds retain full antiviral potency in comparison to the furo parent. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00471-1
• 作为产物：
  描述：

  碘苷 在 吡啶 、 tetraphosphorus decasulfide 作用下， 以 1,4-二氧六环 为溶剂， 反应 6.5h， 生成 3',5'-di-O-acetyl-5-iodo-4-thio-2'-deoxyuridine
  参考文献：
  名称：

  5-取代-4-硫代嘧啶核苷核磁共振谱的系统归属

  摘要：

  使用 NMR 光谱对 5-取代-4-硫代嘧啶核苷（核糖核苷和 2'-脱氧核苷）进行明确表征。5-溴-4-硫尿苷和相关核苷的所有质子和碳信号的分配是通过 COZY 和 HMQC 技术系统地进行并牢固建立的。比较了各种 4-硫代嘧啶核苷的 NMR 数据，并讨论了关键影响因素。这里介绍的方法适用于其他修饰的核苷和核苷酸，以及核碱基。版权所有 © 2013 John Wiley & Sons, Ltd.

  DOI：

  10.1002/mrc.3980

文献信息

• Thionation Using Fluorous Lawesson's Reagent
  作者：Zoltán Kaleta、Brian T. Makowski、Tibor Soós、Roman Dembinski

  DOI：10.1021/ol060208a

  日期：2006.4.1

  [reaction: see text] Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N'-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous

  [反应：参见正文]使用Lawesson试剂的荧光类似物，酰胺化亚酰胺，1,4-二酮，N-（2-氧代烷基）酰胺，N，N'-酰基肼和酰基保护的尿苷硫代酰胺，噻吩，1,3-噻唑，1,3,4-噻二唑和酰基保护的4-硫代尿苷。在大多数情况下，通过简单的过滤（氟固相萃取）就可以实现高产率的最终产物分离。
• 5-Iodo-4-thio-2′-Deoxyuridine as a Sensitizer of X-ray Induced Cancer Cell Killing
  作者：Samanta Makurat、Paulina Spisz、Witold Kozak、Janusz Rak、Magdalena Zdrowowicz

  DOI：10.3390/ijms20061308

  日期：——

  Nucleosides, especially pyrimidines modified in the C5-position, can act as radiosensitizers via a mechanism that involves their enzymatic triphosphorylation, incorporation into DNA, and a subsequent dissociative electron attachment (DEA) process. In this paper, we report 5-iodo-4-thio-2′-deoxyuridine (ISdU) as a compound that can effectively lead to ionizing radiation (IR)-induced cellular death, which is proven by a clonogenic assay. The test revealed that the survival of cells, pre-treated with 10 or 100 µM solution of ISdU and exposed to 0.5 Gy of IR, was reduced from 78.4% (for non-treated culture) to 67.7% and to 59.8%, respectively. For a somewhat higher dose of 1 Gy, the surviving fraction was reduced from 68.2% to 54.9% and to 40.8% for incubation with 10 or 100 µM ISdU, respectively. The cytometric analysis of histone H2A.X phosphorylation showed that the radiosensitizing effect of ISdU was associated, at least in part, with the formation of double-strand breaks. Moreover, the cytotoxic test against the MCF-7 breast cancer cell line and human dermal fibroblasts (HDFa line) confirmed low cytotoxic activity of ISdU. Based on the results of steady state radiolysis of ISdU with a dose of 140 Gy and quantum chemical calculations explaining the origin of the MS detected radioproducts, the molecular mechanism of sensitization by ISdU was proposed. In conclusion, we found ISdU to be a potential radiosensitizer that could improve anticancer radiotherapy.

  核苷，尤其是在C5位置改性的嘧啶，可以通过其酶促三磷酸化、纳入DNA和随后的解离性电子附着（DEA）过程作为放射增敏剂。在本文中，我们报告5-碘-4-硫-2'-脱氧尿嘧啶（ISdU）是一种可以有效引起电离辐射（IR）诱导的细胞死亡的化合物，这已通过克隆形成实验证明。测试显示，预处理10或100微米ISdU溶液并暴露于0.5格雷（Gy）IR的细胞的存活率从未经处理的培养基的78.4％降至67.7％和59.8％。对于稍高的1 Gy剂量，存活率从68.2％降至分别为54.9％和40.8％的10或100微米ISdU孵育。组蛋白H2A.X磷酸化的细胞学分析表明，ISdU的放射增敏效应至少部分与双链断裂的形成有关。此外，对MCF-7乳腺癌细胞系和人类皮肤成纤维细胞（HDFa系）的细胞毒性测试证实了ISdU的低细胞毒性活性。根据ISdU的稳态辐解和量子化学计算的结果，解释了MS检测到的放射性产物的起源，提出了ISdU的增敏分子机制。总之，我们发现ISdU是一种潜在的放射增敏剂，可以改善抗癌放射治疗。
• 5-Iodo-4-thio-2′-deoxyuridine: Synthesis, Structure, and Cytotoxic Activity
  作者：Xiao-Hui Zhang、Hong-Yan Yin、Giuseppe Trigiante、Reto Brem、Peter Karran、Mateusz B. Pitak、Simon J. Coles、Yao-Zhong Xu

  DOI：10.1246/cl.140965

  日期：2015.2.5

  The novel nucleoside 5-iodo-4-thio-2′-deoxyuridine (4) was synthesized and fully characterized by IR, NMR, and MS. Its structure was determined by single-crystal X-ray diffraction. Compound 4 absorbs strongly at 346 nm and is minimally toxic to human tumour cells, but its cytotoxicity is substantially enhanced by low dose UVA radiation. The combined use of 4 and UVA offers a promising route to selectively and effectively kill proliferating cells.

  新型核苷 5-碘-4-硫代-2′-脱氧尿苷（4）经合成并通过红外光谱、核磁共振和质谱得到充分表征。其结构通过单晶 X 射线衍射测定。化合物 4 在 346 nm 处有强吸收，对人类肿瘤细胞毒性极低，但低剂量 UVA 辐射可显著增强其细胞毒性。4 和 UVA 的联合使用为选择性和有效地杀死增殖细胞提供了有前景的途径。
• Excited States of Thio-2′-deoxyuridine Bearing an Extended π-Conjugated System: 3′,5′-Di-<i>O</i>-acetyl-5-phenylethynyl-4-thio-2′-deoxyuridine
  作者：Daiki Nonoshita、Wataru Kashihara、Kazuhito Tanabe、Tasuku Isozaki、Yao−Zhong Xu、Tadashi Suzuki

  DOI：10.1021/acs.jpca.0c09343

  日期：2021.1.21

  The quantum yield of intersystem crossing and the quantum yield of singlet molecular oxygen formation (ϕΔ) under an oxygen atmosphere were also determined. The ϕΔ value of the new thio-2′-deoxyuridine was found to be substantially higher than all reported values of other thio-2′-deoxyribonucleosides in low oxygen concentrations similar to cancer cell environments. The fluorescence quantum yield depended

  成功合成了一个新的带有扩展的π-共轭基团的硫代-2'-脱氧尿苷：3'，5'-二-O-乙酰基-5-苯基乙炔基-4-硫代-2'-脱氧尿苷。thio-2'-脱氧尿苷衍生物在UVA区域具有较大的红移吸收带，并且还显示荧光，这是硫代核碱基/硫代核苷中罕见的光特性。硫-2'-脱氧尿苷的三重态-三重态吸收光谱和速率常数（三重态的固有衰减速率常数，自猝灭速率常数和三重态的氧分子猝灭速率常数）通过瞬态吸收光谱法获得。系统间交叉的量子产率和单线态分子氧形成的量子产率（ϕΔ还测定了在氧气气氛下的）。的φ Δ新硫代-2'-脱氧尿苷的值被发现是比所有报道在低的氧浓度类似于癌细胞环境中的其它硫基-2'-脱氧核糖核苷的值高得多。荧光量子产率取决于激发波长，揭示了在较高激发单重态下的某些光化学反应。然而，当与非共振双光子吸收激发到更高的激发态，则φ Δ硫代-2'-脱氧尿苷衍生物被发现保持足够大。这些发现对于开发基于硫-2