1-[2-bromo-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-1-pivaloyloxy-α-D-ribofuranosyl]uracil

• 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-[2-bromo-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-1-pivaloyloxy-α-D-ribofuranosyl]uracil
• 英文别名: [(2R,3R,4R,5R)-3-bromo-4-[tert-butyl(dimethyl)silyl]oxy-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-2-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl] 2,2-dimethylpropanoate
• 化学式: C₂₆H₄₇BrN₂O₇Si₂
• 分子量: 635.743
• InChiKey: NEFGMZXTUSSKLG-REMZYBCOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.31
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-[3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-2-bromo-D-erythro-pento-1-enofuranosyl]uracil 在 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 反应 1.25h， 生成 1-<2-Bromo-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-1-(pivaloyloxy)-β-D-arabinofuranosyl>uracil 、 1-[2-bromo-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-1-pivaloyloxy-α-D-ribofuranosyl]uracil
  参考文献：
  名称：

  通过同步消除 2'-卤代-2'-脱氧-1'-新戊酰氧基尿嘧啶核苷的新戊酸合成 2'-卤代-1',2'-不饱和尿苷衍生物的替代方法：制备其 2' -C-支链核苷

  摘要：

  摘要 已开发出一种制备 2'-溴-(5b) 和 2'-碘-(5c) 1',2'-不饱和尿嘧啶核苷的替代方法。该方案基于从 2'-溴-(7a,b) 和 2'-碘-(9a,b) 1'-新戊酰氧基-2'-脱氧尿苷衍生物中同步消除新戊酸，这些衍生物衍生来自 3',5'-双-O-TBDMS-1',2'-不饱和尿苷 1 的卤代新戊酰氧基化。 化合物 5b 和 5c 被证明可作为相应的 2'-C-支链 1' 的通用合成子,2'-不饱和尿嘧啶核苷，通过钯催化的交叉偶联或卤素-锂交换反应。图形概要

  DOI：

  10.1080/15257770.2019.1641724

文献信息

• 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.
• Anomeric manipulation of nucleosides: Stereosepecific entry to 1′-C-branched uracil nucleosides
  作者：Kazuhiro Haraguchi、Yoshiharu Itoh、Hiromichi Tanaka、Kentaro Yamaguchi、Tadashi Miyasaka

  DOI：10.1016/s0040-4039(00)91829-x

  日期：1993.10

  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.
• An alternative method for the synthesis of 2′-halogeno-1′,2′-unsaturated uridine derivatives through <i>syn</i>-elimination of pivalic acid of 2′-halogeno- 2′-deoxy-1′-pivaloyloxyuracil nucleoside: preparation of its 2′-<i>C</i>-branched nucleosides
  作者：Kazuhiro Haraguchi、Eisen Gen、Hiroki Kumamoto、Yoshiharu Itoh、Hiromichi Tanaka

  DOI：10.1080/15257770.2019.1641724

  日期：2020.2.20

  Abstract An alternative method for the preparation of 2′-bromo- (5b) and 2′-iodo- (5c) 1′,2′-unsaturated uracil nucleosides has been developed. The protocol was on the basis of the syn-elimination of pivalic acid from 2′-bromo-(7a,b) and 2′-iodo-(9a,b) 1′-pivaloyloxy-2′-deoxyuridine derivatives, which were derived from the halo-pivaloyloxylation of 3′,5′-bis-O-TBDMS-1′,2′-unsaturated uridine 1. Compounds

  摘要 已开发出一种制备 2'-溴-(5b) 和 2'-碘-(5c) 1',2'-不饱和尿嘧啶核苷的替代方法。该方案基于从 2'-溴-(7a,b) 和 2'-碘-(9a,b) 1'-新戊酰氧基-2'-脱氧尿苷衍生物中同步消除新戊酸，这些衍生物衍生来自 3',5'-双-O-TBDMS-1',2'-不饱和尿苷 1 的卤代新戊酰氧基化。 化合物 5b 和 5c 被证明可作为相应的 2'-C-支链 1' 的通用合成子,2'-不饱和尿嘧啶核苷，通过钯催化的交叉偶联或卤素-锂交换反应。图形概要