1'-cyano-2'-deoxy-2'β-bromouridine | 153959-67-2

• 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: 1'-cyano-2'-deoxy-2'β-bromouridine
• 英文别名: (2R,3S,4R,5R)-3-bromo-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-(2,4-dioxopyrimidin-1-yl)oxolane-2-carbonitrile
• CAS: 153959-67-2
• 化学式: C₂₂H₃₈BrN₃O₅Si₂
• 分子量: 560.636
• InChiKey: GRVPOOPWWBOLCM-YDGKCNFYSA-N

物化性质

• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.29
• 重原子数：
  33
• 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：

  1'-cyano-2'-deoxy-2'β-bromouridine 在 氟化铵 、 air 、 偶氮二异丁腈 、 三(三甲基硅基)硅烷 、 水 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 32.08h， 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：

  三甲基氰硅烷 、 1-<2-Bromo-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-1-(pivaloyloxy)-β-D-arabinofuranosyl>uracil 在 四氯化锡 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以80%的产率得到1'-cyano-2'-deoxy-2'β-bromouridine
  参考文献：
  名称：

  Anomeric manipulation of nucleosides: Stereosepecific entry to 1′-C-branched uracil nucleosides

  摘要：

  Uracil nucleosides variously branched at die anomeric position have been synthesized through stereoselective bromo-pivaloyloxylation of a 1',2'-unsaturated derivative and successive SnCl4-promoted nucleophilic substitution with organosilicon reagents. This constitutes the first example of C-C bond formation at the anomeric position of nucleoside.

  DOI：

  10.1016/s0040-4039(00)91829-x

文献信息

• Synthesis and Biological Evaluation of Novel 1′‐Branched and Spironucleoside Analogues
  作者：Chryssostomos Chatgilialoglu、Carla Ferreri、Thanasis Gimisis †、Marinella Roberti、Jan Balzarini、Erik De Clercq

  DOI：10.1081/ncn-200031391

  日期：2004.1.1

  Novel anomeric spironucleosides and 1′‐cyano‐2′,3′‐didehydro‐2′,3′‐dideoxyuridine, a structural analogue of known anti‐HIV agents, were prepared by nucleophilic addition of organolithium reagents to 1′‐cyano‐2′‐deoxy‐ and 1′‐cyano‐2′‐deoxy‐2′β‐bromo‐uridine derivatives, respectively. The yield and distribution of products depended on the reaction conditions, which were studied in detail. Although none

  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。
• Divergent and Stereocontrolled Approach to the Synthesis of Uracil Nucleosides Branched at the Anomeric Position
  作者：Yoshiharu Itoh、Kazuhiro Haraguchi、Hiromichi Tanaka、Eisen Gen、Tadashi Miyasaka

  DOI：10.1021/jo00108a031

  日期：1995.2

  Electrophilic addition of NBS/pivalic acid (bromopivaloyloxylation) to 1-[3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-D-erythro-pent- 1-enofuranosyl]uracil (2), readily accessible from O-2,2'-anhydro-uridine, furnished 1-[2-bromo-3,5-bis-O-(tert-butyldimethyylsilyl)-2-deoxy-1-(pivaloyloxy)-beta-D-ara-binofuranosyl]uracil (7) stereoselectively. This compound (7), having a leaving group at the 1'-position as well as 2'-beta-Br that could exert anchimeric assistance, serves as versatile intermediate for the stereocontrolled synthesis of various types of 1'-C-branched derivatives through nucleophilic substitutions by the use of organosilicon and organoaluminum reagents. The whole sequence constitutes the first example of the conversion of a naturally-occurring nucleoside to the analogues branched at the anomeric position.
• Stereoselective Synthesis of 1'-C-Branched Uracil Nucleosides from Uridine
  作者：Kazuhiro Haraguchi、Yoshiharu Itoh、Hiromichi Tanaka、Tadashi Miyasaka

  DOI：10.1080/15257779508012398

  日期：1995.5.1

  Face-selective electrophilic addition (bromo-pivaloyloxylation) to 1-[3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-D-erythro-pent-1-enofuranosyl]uracil (1), when combined with nucleophilic substitution using organosilicon or organoaluminum reagents, provides a new and highly divergent C-C bond forming method at the anomeric position.
• 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.