3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine | 156897-72-2

• 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: 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine
• 英文别名: [(2R,3S,5R)-5-(3-benzoyl-5-iodo-2,4-dioxopyrimidin-1-yl)-3-benzoyloxyoxolan-2-yl]methyl benzoate
• CAS: 156897-72-2
• 化学式: C₃₀H₂₃IN₂O₈
• 分子量: 666.426
• InChiKey: ZZDNRVXYUMJTDZ-ISJGIBHGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  120
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine 在 bis-triphenylphosphine-palladium(II) chloride 氢氧化钾 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 1.0h， 生成 3-benzoyl-5-(E)-(ν-trifluoromethyl-α,ν-butadienyl)-2'-deoxyuridine
  参考文献：
  名称：

  钯催化的（E）-（3-三氟甲基-1,3-丁二烯基）二异丙氧基硼烷与乙烯基卤化物的交叉偶联。有效的立体定向合成三氟甲基化的1,3,5-三烯

  摘要：

  通过钯催化的（E）-（3-三氟甲基-1,3-丁二烯基）二-异丙氧基硼烷与钯的交叉偶联，以高产率立体定向合成了具有CF 3基团的1,3,5-三烯。卤化物。作为合成应用，通过该方法合成了新型的含CF 3的核苷衍生物。

  DOI：

  10.1016/0022-1139(93)02989-r
• 作为产物：
  描述：

  3-N-benzoyl-3',5'-di-O-benzoyl-2'-deoxyuridine 在 一氯化碘 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine
  参考文献：
  名称：

  钯催化的（E）-（3-三氟甲基-1,3-丁二烯基）二异丙氧基硼烷与乙烯基卤化物的交叉偶联。有效的立体定向合成三氟甲基化的1,3,5-三烯

  摘要：

  通过钯催化的（E）-（3-三氟甲基-1,3-丁二烯基）二-异丙氧基硼烷与钯的交叉偶联，以高产率立体定向合成了具有CF 3基团的1,3,5-三烯。卤化物。作为合成应用，通过该方法合成了新型的含CF 3的核苷衍生物。

  DOI：

  10.1016/0022-1139(93)02989-r

文献信息

• Asymmetric Induction and Enantiodivergence in Catalytic Radical C–H Amination via Enantiodifferentiative H-Atom Abstraction and Stereoretentive Radical Substitution
  作者：Kai Lang、Sebastian Torker、Lukasz Wojtas、X. Peter Zhang

  DOI：10.1021/jacs.9b05850

  日期：2019.8.7

  proven difficult, the judicious use of HuPhyrin ligand by tuning the bridge length and other remote non-chiral elements allows for controlling both the degree and sense of asymmetric induction in a systematic manner. This effort leads to successful development of new Co(II)-based catalytic systems that are highly effective for enantiodivergent radical 1,5-C-H amination, producing both enantiomers of the

  对映选择性的控制仍然是自由基化学中的主要挑战。金属自由基催化 (MRC) 的出现为解决这一问题和其他突出问题提供了一种概念上的新策略。通过使用 D2 对称手性酰胺卟啉作为支持配体，基于 Co(II) 的 MRC 能够开发具有独特反应性和选择性特征的不对称自由基转化的新催化系统。在可微调腔环境的新一代 HuPhyrin 手性配体的支持下，共中心 d 自由基能够解决需要精确控制基本自由基过程的挑战性问题。正如氨磺酰叠氮化物的不对称 1,5-CH 胺化所展示的那样，其对映控制已被证明是困难的，通过调整桥长度和其他远程非手性元素明智地使用 HuPhyrin 配体允许以系统的方式控制不对称诱导的程度和意义。这一努力导致成功开发了新的基于 Co(II) 的催化系统，该系统对对映发散自由基 1,5-CH 胺化非常有效，产生具有优异对映选择性的应变 5 元环磺酰胺的两种对映异构体。详细的氘标记研究以及 DFT
• CATALYTIC SYSTEMS FOR STEREOSELECTIVE SYNTHESIS OF CHIRAL AMINES BY ENANTIODIVERGENT RADICAL C-H AMINATION
  申请人：Trustees of Boston College

  公开号：US20200317627A1

  公开（公告）日：2020-10-08

  In one aspect, the disclosure relates to a mode of asymmetric induction in radical processes based on sequential combination of enantiodifferentiative H-atom abstraction and stereoretentive radical substitution. Also disclosed is an asymmetric system for stereoselective synthesis of strained 5-membered cyclic sulfamides via radical 1,5-C—H amination of sulfamoyl azides. The disclosed metalloradical system can control the degree and sense of asymmetric induction in the catalytic radical C—H amination in a systematic manner. The disclosed system is applicable to a broad scope of substrates with different types of C(sp 3 )-H bonds and exhibits reactivity and selectivity, providing access to both enantiomers of useful 5-membered cyclic sulfamides in a highly enantioenriched form. Also disclosed are catalysts useful in these processes. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.

  在一个方面，该公开涉及基于手性差异化氢原子抽取和立体保留自由基取代的顺序组合的不对称诱导模式在自由基过程中的应用。还公开了一种用于通过磺胺酰叠氮化物的自由基1,5-C—H胺化对合成受限的5-成员环磺胺的立体选择性合成的不对称系统。所公开的金属自由基系统可以以系统化的方式控制催化自由基C—H胺化中的不对称诱导程度和方向。所公开的系统适用于具有不同类型的C(sp3)-H键的广泛底物范围，并表现出反应性和选择性，以高度手性富集形式提供对有用的5-成员环磺胺的两个对映体的访问。还公开了在这些过程中有用的催化剂。本摘要旨在作为在特定领域搜索的扫描工具，不打算限制本公开。
• Chemoselective Amination of Propargylic C(sp³)H Bonds by Cobalt(II)-Based Metalloradical Catalysis
  作者：Hongjian Lu、Chaoqun Li、Huiling Jiang、Christopher L. Lizardi、X. Peter Zhang

  DOI：10.1002/anie.201400557

  日期：2014.7.1

  Highly chemoselective intramolecular amination of propargylic C(sp3)H bonds has been demonstrated for N‐bishomopropargylic sulfamoyl azides through cobalt(II)‐based metalloradical catalysis. Supported by D2h‐symmetric amidoporphyrin ligand 3,5‐DitBu‐IbuPhyrin, the cobalt(II)‐catalyzed CH amination proceeds effectively under neutral and nonoxidative conditions without the need of any additives, and

  已经通过钴 (II) 基金属基催化对 N-双同炔氨磺酰基叠氮化物证明了炔丙 C(sp 3 )  H 键的高度化学选择性分子内胺化。在 D 2h对称酰胺卟啉配体 3,5-Di t Bu-IbuPhyrin 的支持下，钴 (II) 催化的 C  H 胺化在中性和非氧化条件下有效进行，无需任何添加剂，并生成 N 2作为唯一的副产品。金属自由基胺化适用于二级和三级炔丙C H 底物具有异常高的官能团耐受性，从而为功能化炔丙胺衍生物的高产合成提供了一种直接方法。
• Synthesis of 5-Fluoroalkylated Pyrimidine Nucleosides via Negishi Cross-Coupling
  作者：Ann-Marie Chacko、Wenchao Qu、Hank F. Kung

  DOI：10.1021/jo800444y

  日期：2008.7.1

  5-Fluoroalkylated pyrimidine nucleosides (1) have potential as therapeutic agents and molecular imaging agents targeting HSV1-tk suicide gene therapy. Thus, straightforward preparation of 5-fluoroalkylated nucleoside derivatives has been developed. Reported herein are the first examples of Pd-catalyzed Negishi cross-coupling of 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxyuridine (2a) and 3-N-benzoyl-3',5'-di-O-benzoyl-5-iodo-2'-deoxy-2'-fluoroarabinouridine (2b) with unactivated CSp(3) fluoroalkylzinc bromides. This paper demonstrates the first synthesis of six 5-fluoroalkyl-2'-deoxypyrimidine nucleoside derivatives with three to five methylene chain lengths (5). Furthermore, this methodology has been extended to create a series of 13 5-alkyl-substituted nucleosides, including the target nucleosides 5 and 5-silyloxypropyl and 5-cyanobutyl derivatives.
• Synthesis and in Vitro Evaluation of 5-[¹⁸F]Fluoroalkyl Pyrimidine Nucleosides for Molecular Imaging of Herpes Simplex Virus Type 1 Thymidine Kinase Reporter Gene Expression
  作者：Ann-Marie Chacko、Wenchao Qu、Hank F. Kung

  DOI：10.1021/jm800501d

  日期：2008.9.25

  Two novel series of 5-fluoroalkyl-2'-deoxyuridines (FPrDU, FBuDU, FPeDU) and 2'-fluoro-2'-deoxy-5-fluoroalkylarabinouridines (FFPrAU, FFBuAU, FFPeAU) that have three, four, or five methylene units (propyl, butyl, or pentyl) at C-5 were prepared and tested as reporter probes for imaging herpes simplex virus type I thymidine kinase (HSV1-tk) gene expression. The Negishi coupling methodology was employed in efficiently synthesizing the radiolabeling precursors. All six 5-[F-18]fluoroalkyl pyrimidines were readily prepared from 3-N-benzoyl-3',5'-di-O-benzoyl-protected 5-O-mesylate Precursors in 17-35% radiochemical yield (decay-corrected). In vitro studies highlighted that all six [F-18]-labeled nucleosides selectively accumulated in cells expressing the HSV1-TK protein and there was negligible uptake in control cells. [F-18]FPrDU, [F-18]FBuDU, [F-18]FPeDU, and [F-18]FFBuAU had the best uptake profiles. Despite their selective accumulation in HSV1-tk-expressing cells, all 5-fluoroalkyl pyrimidine nucleosides had low-to-negligible cytotoxic activity (CC50 > 1000-1209 mu M). Ultimately, the results demonstrated that 5-[F-18]fluoropropyl, [F-18]fluorobutyl, and [F-18]fluoropentyl pyrimidine nucleosides have the potential to be in vivo HSV1-TK PET reporter probes over a dynamic range of reporter gene expression levels.