2',5'-di-O-(tert-butyldimethylsilyl)-1'-C-cyano-2'-deoxyuridine | 167023-13-4

• 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: 2',5'-di-O-(tert-butyldimethylsilyl)-1'-C-cyano-2'-deoxyuridine
• 英文别名: (2S,4S,5R)-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-(2,4-dioxopyrimidin-1-yl)oxolane-2-carbonitrile
• CAS: 167023-13-4
• 化学式: C₂₂H₃₉N₃O₅Si₂
• 分子量: 481.74
• InChiKey: YLCMPVOMEVMOFU-JKSBSHDWSA-N

物化性质

• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.91
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2',5'-di-O-(tert-butyldimethylsilyl)-1'-C-cyano-2'-deoxyuridine 在 氟化铵 、 air 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 30.08h， 生成 D-(+)-核糖酸-gamma-内酯
  参考文献：
  名称：

  Fate of the C-1′ peroxyl radical in the 2′-deoxyuridine system

  摘要：

  光生2-脱氧尿苷-1-基自由基与水中的分子氧反应形成2-脱氧核糖酸内酯的机理已经过研究。

  DOI：

  10.1039/a802375a
• 作为产物：
  描述：

  1'-cyano-2'-deoxy-2'β-bromouridine 在 偶氮二异丁腈 、 三(三甲基硅基)硅烷 作用下， 以 甲苯 为溶剂， 反应 1.5h， 以94%的产率得到2',5'-di-O-(tert-butyldimethylsilyl)-1'-C-cyano-2'-deoxyuridine
  参考文献：
  名称：

  新型 1'-支链和螺核苷类似物的合成和生物学评价

  摘要：

  通过将有机锂试剂亲核加成到 1'-氰基-2 上制备了新型异头螺核苷和 1'-氰基-2',3'-didehydro-2',3'-dideoxyuridine，一种已知抗 HIV 药物的结构类似物'-deoxy- 和 1'-cyano-2'-deoxy-2'β-bromo-uridine 衍生物，分别。产物的产率和分布取决于反应条件，对此进行了详细研究。尽管这些化合物都没有表现出抗病毒活性，但有两种化合物对鼠白血病和人 T 淋巴细胞都表现出细胞抑制活性。†也是通讯作者。

  DOI：

  10.1081/ncn-200031391

文献信息

• Models of DNA C1‘ Radicals. Structural, Spectral, and Chemical Properties of the Thyminylmethyl Radical and the 2‘-Deoxyuridin-1‘-yl Radical
  作者：Chryssostomos Chatgilialoglu、Carla Ferreri、Rita Bazzanini、Maurizio Guerra、Seung-Yong Choi、Calvin J. Emanuel、John H. Horner、Martin Newcomb

  DOI：10.1021/ja001783r

  日期：2000.10.1

  thyminylmethyl radical and the 2‘-deoxyuridin-1‘-yl radical were studied. The former radical was produced in laser flash photolysis (LFP) studies from two precursors derived from thyminylacetic acid, the N-hydroxypyridine-2-thione ester (PTOC ester), and the phenylselenyl ester. The thyminylmethyl radical has an absorbance in the range 315−340 nm. The rate constant for its reaction with octadecanethiol

  研究了胸腺嘧啶甲基自由基和 2'-脱氧尿苷-1'-基自由基。前一种自由基是在激光闪光光解 (LFP) 研究中从胸腺嘧啶乙酸、N-羟基吡啶-2-硫酮酯 (PTOC 酯) 和苯基硒基酯衍生的两种前体产生的。胸腺嘧啶甲基自由基在 315-340 nm 范围内具有吸光度。在环境温度下，通过 LFP 方法确定其与十八烷硫醇在 THF 中的反应速率常数为 (3.1 ± 0.6) × 107 M-1 s-1。2'-deoxyuridin-1'-yl 自由基是从相应的 C1' 叔丁基酮、1'-pivaloyl-2'-deoxyuridine 的两种非对映异构体的大量光解中产生的，并且在 LFP 研究中来自一种非对映异构体。用 2-巯基乙醇、半胱氨酸或谷胱甘肽捕获该 C1' 基团得到 2'-脱氧尿苷的两个端基异构体；每种情况下的产物比率相似，并且对前体特性或硫醇浓度不敏感。2'-脱氧尿苷-1'-基自由基与硫醇和金属离子反应的速率常数为
• Competitive Inhibition of Uracil DNA Glycosylase by a Modified Nucleotide Whose Triphosphate is a Substrate for DNA Polymerase
  作者：Haidong Huang、James T. Stivers、Marc M. Greenberg

  DOI：10.1021/ja807705z

  日期：2009.2.4

  Base excision repair (BER) enzymes are attractive targets for antiviral and anticancer agents. A number of nucleotides and nucleotide analogues are potent competitive inhibitors of BER glycosylases when they are incorporated into synthetic oligonucleotides. However, these molecules often are not substrates for DNA polymerases, which limits their utility in cells and as potential therapeutic agents. 1'-Cyano-2'-deoxyuridine (CNdU) is a nanomolar competitive inhibitor of uracil DNA glycosylase. In addition, the respective nucleotide triphosphate is accepted as a substrate by the Klenow fragment (exo-) of DNA polymerase I from E. coli. This is the first competitive inhibitor of UDG that is incorporated into DNA by Klenow exo-, a model replicative polymerase. 1'-Cyano-2'-deoxyuridine (CNdU) and related molecules may prove useful as a new family of therapeutic or experimental agents that target DNA repair by using the cells' polymerase(s) to incorporate them into DNA. A potential benefit of such a mechanism is that multiple incorporations can occur for longer DNA molecules leading to amplification of the inhibitory effect beyond that seen here with short DNA duplexes.
• Anionically induced formation of anomeric spironucleosides from 1′-C-cyano-2′-deoxyuridine
  作者：Chryssostomos Chatgilialoglu、Carla Ferreri、Thanasis Gimisis

  DOI：10.1016/s0040-4039(99)00273-7

  日期：1999.4

  The reaction of the 1'-C-cyano-2'-deoxyuridine derivative 1 with organolithium reagents can be favorably tuned to give a new class of anomeric spironucleosides. (C) 1999 Elsevier Science Ltd. All rights reserved.
• Kinetics and Stereoselectivity of Thiol Trapping of Deoxyuridin-1‘-yl in Biopolymers and Their Relationship to the Formation of Premutagenic α-Deoxynucleotides
  作者：Jae-Taeg Hwang、Marc M. Greenberg

  DOI：10.1021/ja990152y

  日期：1999.5.1

  alpha-Deoxynucleotides are potentially deleterious lesions when produced in DNA. They are presumably formed in part via misrepair of the respective C1'-nucleotide radicals by thiols. However, the selectivity and extent to which these lesions are formed via this pathway has not been ascertained. Using the ability to independently generate deoxyuridin-1'-yl (4) at a defined site in a biopolymer, we have determined that thiol trapping in duplex DNA occurs with high stereoselectivity from the ct-face, resulting in restoration of the naturally occurring beta-deoxynucleotide. The observed stereoselectivity of thiol trapping in duplex DNA suggests that 4 is intrahelical. The rate constant for hydrogen atom donation to 4 is reduced 2-3-fold in double-stranded DNA compared to single-stranded DNA. This decrease is attributed to the relative inaccessibility of the C1'-position in duplex DNA. The combination of these two properties of 4 indicates that, at O-2 concentrations present in aerated water, alpha-deoxynucleotide formation should constitute a minor component of the reactivity of C1'-radicals. Accordingly, the chemical biology of other lesions derived from formal damage at C1'-position could be significant.
• Synthesis and Biological Evaluation of 1′-<i>C</i>-Cyano-Pyrimidine Nucleosides
  作者：Yuichi Yoshimura、Fumitaka Kano、Shuichi Miyazaki、Noriyuki Ashida、Shinji Sakata、Kazuhiro Haraguchi、Yoshiharu Itoh、Hiromichi Tanaka、Tadashi Miyasaka

  DOI：10.1080/07328319608002386

  日期：1996.1

  2'-Deoxy-, 2'-bromo-, and arabine-1'-C-cyano-pyrimidine nucleosides were synthesized from O-2,2'-cyclouridine. Incorporation of cyano group at the anomeric position was achieved by treatment of 1',2'-unsaturated uridine with NBS in the presence of pivalic acid followed by TMS-cyanide and stannic chloride. Antineoplastic and antiviral activities of those compounds are also discussed.