N-benzyloxy-3-phenyl-propionamide | 22426-87-5

• 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-benzyloxy-3-phenyl-propionamide
• 英文别名: 3-phenyl-N-phenylmethoxypropanamide
• CAS: 22426-87-5
• 化学式: C₁₆H₁₇NO₂
• mdl: MFCD20760407
• 分子量: 255.316
• InChiKey: NCYYNUXNNJCXKL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.187
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-benzyloxy-3-phenyl-propionamide 在 palladium 10% on activated carbon 、 甲酸铵 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以234 mg的产率得到N-羟基-3-苯基丙酰胺
  参考文献：
  名称：

  Synthesis and Biological Evaluation of N-Hydroxyphenylacrylamides and N-Hydroxypyridin-2-ylacrylamides as Novel Histone Deacetylase Inhibitors

  摘要：

  The historic deacetylases (HDACs) are able to regulate gene expression, and historic deacetylase inhibitors (HDACi) emerged as a new class of agents in the treatment of cancer as well as other human disorders such as neurodegenerative diseases. In the present investigation, we report on the synthesis and biological evaluation of compounds derived from the expansion of a HDAC inhibitor scaffold having N-hydroxy-3-phenyl-2-propenamide and N-hydroxy-3-(pyridin-2-yl)-2-propenamide as core structures and containing a phenyloxopropenyl moiety, either unsubstituted or substituted by a 4-methylpiperazin-1-yl or 4-methylpiperazin-1-ylmethyl group. The compounds were evaluated for their ability to inhibit nuclear HDACs, as well as for their in vitro antiproliferative activity. Moreover, their metabolic stability in microsomes and aqueous Solubility were studied and selected compounds were further characterized by in vivo pharmacokinetic experiments. These compounds showed a remarkable stability in vivo, compared to hydroxamic acid HDAC inhibitors that have already entered clinical trials. The representative compound 30b showed in vivo antitumor activity in a human colon carcinoma xenograft model.

  DOI：

  10.1021/jm901502p
• 作为产物：
  描述：

  O-苄基羟胺 、 3-苯丙酸乙酯 在 三甲基铝 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-benzyloxy-3-phenyl-propionamide
  参考文献：
  名称：

  A Novel and Practical Synthesis of l-Hexoses from d-Glycono-1,5-lactones

  摘要：

  A novel and efficient conversion of D-glycono-1,5-lactones into the corresponding L-sugars is described. The important intermediate, delta-hydroxyalkoxamates, was provided by a practical alkoxyamination of D-glycono-1,5-lactones mediated by Me3Al. In contrast to the preparation of beta-lactam skeletons from beta-hydroxyalkoxamates, the cyclization of delta-hydroxyalkoxamates under Mitsunobu conditions resulted in O-alkylation rather than N-alkylation. It is noteworthy that delta-hydroxyalkoxamates derived from D-mannono-1,5-lactones afforded the O-alkylation product in 91% yield. None of the N-alkylation product was detected in this case. These O-cyclized oximes, in which the inversion of the configuration at C5 was secured, were efficiently converted into the L-sugars.

  DOI：

  10.1021/ja992808t

文献信息

• A Convenient Method for the Conversion of <i>N</i>-Acyloxazolidinones to Hydroxamic Acids
  作者：Mukund P. Sibi、Hikaru Hasegawa、Sandeep R. Ghorpade

  DOI：10.1021/ol0263301

  日期：2002.10.1

  Treatment of N-acyloxazolidinones with hydroxylamines using samarium triflate as a Lewis acid provides the corresponding hydroxamic acids in 50-98% yields at room temperature. The conversion proceeds with high degree of chemoselectivity and without racemization of chiral centers alpha- to the acyl group. [reaction: see text]

  使用三氟甲磺酸sa作为路易斯酸，用羟胺处理N-酰基恶唑烷酮，在室温下以50-98％的收率提供相应的异羟肟酸。转化以高度的化学选择性进行，并且手性中心不外消旋地从α到酰基。[反应：看文字]
• Generation of Mixed Anhydrides via Oxidative Fragmentation of Tertiary Cyclopropanols with Phenyliodine(III) Dicarboxylates
  作者：Dzmitry M. Zubrytski、Gábor Zoltán Elek、Margus Lopp、Dzmitry G. Kananovich

  DOI：10.3390/molecules26010140

  日期：——

  sulfur-centered nucleophiles (primary and secondary amines, hydroxylamines, primary alcohols, phenols, thiols). Intramolecular acylation yielding macrocyclic lactones can also be performed. The developed transformation has bolstered the synthetic utility of cyclopropanols as pluripotent intermediates in diversity-oriented synthesis of bioactive natural products and their synthetic congeners. For example,

  在非质子溶剂（二氯甲烷、氯仿、甲苯）中，叔环丙醇与二羧酸苯碘 (III) 的氧化裂解产生混合酸酐。使用带有吸电子羧酸配体（三氟乙酰、2,4,6-三氯苯甲酰基、3-硝基苯甲酰基）的苯碘（III）试剂时，裂解反应特别容易，相应混合酸酐产物的产率为 95-98%。后者可以直接应用于各种以氮、氧和硫为中心的亲核试剂（伯胺和仲胺、羟胺、伯醇、酚、硫醇）的酰化。也可以进行产生大环内酯的分子内酰化。所开发的转化增强了环丙醇作为多能中间体在生物活性天然产物及其合成同源物的多样性导向合成中的合成效用。例如，它成功应用于环肽的最后阶段修饰，以产生已知的组蛋白脱乙酰酶抑制剂的前体。
• Preparation and Thermal Decomposition of N,N'-Diacyl-N,N'-Dialkoxyhydrazines: Synthetic Applications and Mechanistic Insights
  作者：Mauro V. De Almeida、Derek H. R. Barton、Ian Bytheway、J. Albert Ferreira、Michael B. Hall、Wansheng Liu、Dennis K. Taylor、Lisa Thomson

  DOI：10.1021/ja00122a018

  日期：1995.5

  Oxidation of various O-alkyl hydroxamates 1 where R(1) was a keto-methoxime, benzoyl, aryl, or alkyl group with eerie ammonium nitrate (CAN) or nickel peroxide (NiO2 . H2O) leads to the corresponding esters in high yield. This augurs well for the facile synthesis of highly hindered esters. Dimers of type 2 were identified as intermediates in these oxidations, and a combination of experimental and theoretical results suggest that these dimers decompose in a stepwise 1,1-elimination manner via intermediate nitrenes to furnish the esters and not via a stepwise 1,2-elimination sequence as previously thought.
• One-Step Synthesis of <i>O</i>-Benzyl Hydroxamates from Unactivated Aliphatic and Aromatic Esters
  作者：Arnaud Gissot、Alessandro Volonterio、Matteo Zanda

  DOI：10.1021/jo0509713

  日期：2005.8.1

  [GRAPHICS]We have developed a simple and high yielding one-step method for the synthesis of hydroxamate derivatives directly from a broad range of unactivated esters and the anion of O-benzyl-hydroxylamine generated in situ. The reaction takes place in minutes at -78 degrees C. Very importantly, the method was successfully employed with enolizable esters, including chiral alpha-amino acid esters and peptides, with no trace of racemization/epimerization at the a carbon detected.
• A Novel and Practical Synthesis of <scp>l</scp>-Hexoses from <scp>d</scp>-Glycono-1,5-lactones
  作者：Hideyo Takahashi、Yuko Hitomi、Yoshinori Iwai、Shiro Ikegami

  DOI：10.1021/ja992808t

  日期：2000.4.1

  A novel and efficient conversion of D-glycono-1,5-lactones into the corresponding L-sugars is described. The important intermediate, delta-hydroxyalkoxamates, was provided by a practical alkoxyamination of D-glycono-1,5-lactones mediated by Me3Al. In contrast to the preparation of beta-lactam skeletons from beta-hydroxyalkoxamates, the cyclization of delta-hydroxyalkoxamates under Mitsunobu conditions resulted in O-alkylation rather than N-alkylation. It is noteworthy that delta-hydroxyalkoxamates derived from D-mannono-1,5-lactones afforded the O-alkylation product in 91% yield. None of the N-alkylation product was detected in this case. These O-cyclized oximes, in which the inversion of the configuration at C5 was secured, were efficiently converted into the L-sugars.