N-benzyl-N-(tert-butyl)-2-chloroacetamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-benzyl-N-(tert-butyl)-2-chloroacetamide
• 英文别名: N-benzyl-N-tert-butyl-2-chloro-acetamide；N-benzylN-tert.-butyl-2-chloroacetamide；N-BenzylN-tert-butyl-2-chloroacetamide；N-Benzyl-N-tert-butylchloroacetamide；N-benzyl-N-tert-butyl-2-chloroacetamide
• 化学式: C₁₃H₁₈ClNO
• 分子量: 239.745
• InChiKey: QVQIAOBUBDFSCF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-benzyl-N-(tert-butyl)-2-chloroacetamide 在 1-金刚烷甲酸 、 C₇₁H₁₀₈NO₈P 、 caesium carbonate 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 作用下， 以 甲苯 为溶剂， 以93%的产率得到(S)-1-(tert-butyl)-4-phenylazetidin-2-one
  参考文献：
  名称：

  通过对映选择性钯（0）催化的C（sp3）获得β-内酰胺？H烷基化

  摘要：

  β-内酰胺由于具有广泛的生物学活性以及易于发生开环反应，因此是非常重要的结构基序。过渡金属催化的CH功能化已成为实现非常规高效断开连接的策略。与Pd 0催化的CH官能化用于芳基-芳基偶联的显着进展相反，涉及形成饱和C（sp 3）C（sp 3）键的相关反应是难以捉摸的。这里报告的是一个不对称的C使用容易获得的氯乙酰胺底物对β-内酰胺进行H官能化方法。这种转变的重要方面是挑战四元环的C（sp 3）C（sp 3）和应变消除。通常，使用大体积的他达酚亚磷酰胺配体与金刚烷基羧酸作为助催化剂，可以以优异的收率和对映选择性形成β-内酰胺。

  DOI：

  10.1002/anie.201405508
• 作为产物：
  描述：

  N-叔丁基苄胺 、 氯乙酰氯 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 N-benzyl-N-(tert-butyl)-2-chloroacetamide
  参考文献：
  名称：

  通过对映选择性钯（0）催化的C（sp3）获得β-内酰胺？H烷基化

  摘要：

  β-内酰胺由于具有广泛的生物学活性以及易于发生开环反应，因此是非常重要的结构基序。过渡金属催化的CH功能化已成为实现非常规高效断开连接的策略。与Pd 0催化的CH官能化用于芳基-芳基偶联的显着进展相反，涉及形成饱和C（sp 3）C（sp 3）键的相关反应是难以捉摸的。这里报告的是一个不对称的C使用容易获得的氯乙酰胺底物对β-内酰胺进行H官能化方法。这种转变的重要方面是挑战四元环的C（sp 3）C（sp 3）和应变消除。通常，使用大体积的他达酚亚磷酰胺配体与金刚烷基羧酸作为助催化剂，可以以优异的收率和对映选择性形成β-内酰胺。

  DOI：

  10.1002/anie.201405508

文献信息

• Imidazolium salts
  申请人：Janssen Pharmaceutica N.V.

  公开号：US03991202A1

  公开（公告）日：1976-11-09

  Novel quaternary imidazolium salts substituted on one nitrogen of the imidazolium cation with a ##EQU1## group in which each A is an aryl radical and B is an aliphatic, aryl-substituted aliphatic or aromatic radical, said salts being useful as antimicrobial agents.

  新型的四元咪唑盐，其中咪唑阳离子的一个氮原子上取代有一个##EQU1##基团，其中每个A是芳基基团，B是脂肪基、芳基取代的脂肪基或芳基基团，这些盐可用作抗微生物剂。
• Structural Modulation Study of Inhibitory Compounds for Ribonuclease H Activity of Human Immunodeficiency Virus Type 1 Reverse Transcriptase
  作者：Hiroshi Yanagita、Satoshi Fudo、Emiko Urano、Reiko Ichikawa、Masakazu Ogata、Mizuho Yokota、Tsutomu Murakami、Honggui Wu、Joe Chiba、Jun Komano、Tyuji Hoshino

  DOI：10.1248/cpb.60.764

  日期：——

  Reverse transcriptase of human immunodeficiency virus type 1 (HIV-1) has two enzymatic functions. One of the functions is ribonuclease (RNase) H activity concerning the digestion of only RNA of RNA/DNA hybrid. The RNase H activity is an attractive target for a new class of anti-HIV drugs because no approved inhibitor is available now. In our previous studies, an agent bearing 5-nitro-furan-2-carboxylic acid ester core was found from chemical screening and dozens of the derivatives were synthesized to improve compound potency. In this work, some parts of the chemical structure were modulated to deepen our understanding of the structure–activity relationship of the analogous compounds. Several derivatives having nitro-furan-phenyl-ester skeleton were shown to be potent RNase H inhibitors. Attaching methoxy-carbonyl and methoxy groups to the phenyl ring increased the inhibitory potency. No significant cytotoxicity was observed for these active derivatives. In contrast, the derivatives having nitro-furan-benzyl-ester skeleton showed modest inhibitory activities regardless of attaching diverse kinds of functional groups to the benzyl ring. Both the modulation of the 5-nitro-furan-2-carboxylic moiety and the conversion of the ester linkage resulted in a drastic decrease in inhibitory potency. These findings are informative for designing potent inhibitors of RNase H enzymatic activity of HIV-1.

  人类免疫缺陷病毒 1 型（HIV-1）的逆转录酶具有两种酶功能。其中一个功能是核糖核酸酶（RNase）H 活性，它只消化 RNA/DNA 混合体中的 RNA。RNase H 活性是一类新型抗艾滋病毒药物的诱人靶点，因为目前还没有获得批准的抑制剂。在我们以前的研究中，通过化学筛选发现了一种以 5-硝基呋喃-2-羧酸酯为核心的药剂，并合成了数十种衍生物以提高化合物的效力。在这项工作中，我们对部分化学结构进行了调整，以加深对类似化合物结构-活性关系的理解。研究表明，几种具有硝基呋喃-苯基酯骨架的衍生物是有效的 RNase H 抑制剂。在苯基环上连接甲氧基羰基和甲氧基基团可提高抑制效力。这些活性衍生物没有观察到明显的细胞毒性。相比之下，具有硝基呋喃-苄酯骨架的衍生物无论在苄基环上连接何种官能团，都显示出适度的抑制活性。对 5-硝基-呋喃-2-羧基的调节和酯连接的转换都会导致抑制效力的急剧下降。这些发现对设计有效的 HIV-1 RNase H 酶活性抑制剂具有参考价值。
• 一种螺内酰胺环己二烯类化合物的制备方法
  申请人：华南理工大学

  公开号：CN116425666A

  公开（公告）日：2023-07-14

  本发明公开了一种螺内酰胺环己二烯类化合物的制备方法。本发明的螺内酰胺环己二烯类化合物的制备方法包括以下步骤：将N‑苄基‑α‑卤代乙酰胺、β‑二羰基化合物、碱、钯催化剂和双膦配体分散在溶剂中，再光照进行反应，即得螺内酰胺环己二烯类化合物。本发明可以通过N‑苄基‑α‑卤代乙酰胺和β‑二羰基化合物的去芳构化反应一步构建氮杂螺环骨架，原料便宜易得，操作简单，反应条件温和，产物收率高，产物选择性好，具有很好的工业化应用前景。
• Synthesis of α-chloroamides in water
  作者：Andrew J. Harte、Thorfinnur Gunnlaugsson

  DOI：10.1016/j.tetlet.2006.06.090

  日期：2006.8

  The reaction between chloroacetyl chloride and mono- or bis-aliphatic or aromatic amines in water under basic or neutral conditions gives rise to the formation of a variety of functionalized alpha-chloroamides. The resulting products were obtained as solids in moderate to good yields, upon precipitation and isolation by filtration. (c) 2006 Elsevier Ltd. All rights reserved.
• Structural and biochemical study on the inhibitory activity of derivatives of 5-nitro-furan-2-carboxylic acid for RNase H function of HIV-1 reverse transcriptase
  作者：Hiroshi Yanagita、Emiko Urano、Kishow Matsumoto、Reiko Ichikawa、Yoshihisa Takaesu、Masakazu Ogata、Tsutomu Murakami、Hongui Wu、Joe Chiba、Jun Komano、Tyuji Hoshino

  DOI：10.1016/j.bmc.2010.12.011

  日期：2011.1

  Rapid emergence of drug-resistant variants is one of the most serious problems in chemotherapy for HIV-1 infectious diseases. Inhibitors acting on a target not addressed by approved drugs are of great importance to suppress drug-resistant viruses. HIV-1 reverse transcriptase has two enzymatic functions, DNA polymerase and RNase H activities. The RNase H activity is an attractive target for a new class of antiviral drugs. On the basis of the hit chemicals found in our previous screening with 20,000 small molecular-weight compounds, we synthesized derivatives of 5-nitro-furan-2-carboxylic acid. Inhibition of RNase H enzymatic activity was measured in a biochemical assay with real-time monitoring of florescence emission from the digested RNA substrate. Several derivatives showed higher inhibitory activities that those of the hit chemicals. Modulation of the 5-nitro-furan-2-carboxylic moiety resulted in a drastic decrease in inhibitory potency. In contrast, many derivatives with modulation of other parts retained inhibitory activities to varying degrees. These findings suggest the binding mode of active derivatives, in which three oxygen atoms aligned in a straight form at the nitro-furan moiety are coordinated to two divalent metal ions located at RNase H reaction site. Hence, the nitro-furan-carboxylic moiety is one of the critical scaffolds for RNase H inhibition. Of note, the RNase H inhibitory potency of a derivative was improved by 18-fold compared with that of the original hit compound, and no significant cytotoxicity was observed for most of the derivatives showing inhibitory activity. Since there is still much room for modification of the compounds at the part opposite the nitro-furan moiety, further chemical conversion will lead to improvement of compound potency and specificity. (C) 2010 Elsevier Ltd. All rights reserved.