tert-butyl 4-((3-(4-chlorobenzoyl)phenoxy)methyl)piperidine-1-carboxylate | 1372526-57-2

• 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: tert-butyl 4-((3-(4-chlorobenzoyl)phenoxy)methyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[[3-(4-chlorobenzoyl)phenoxy]methyl]piperidine-1-carboxylate
• CAS: 1372526-57-2
• 化学式: C₂₄H₂₈ClNO₄
• 分子量: 429.944
• InChiKey: NAOCDJVDZUYYMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-((3-(4-chlorobenzoyl)phenoxy)methyl)piperidine-1-carboxylate 在 三甲基铝 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.25h， 生成 (S)-(4-chlorophenyl)(3-((1-(2-hydroxyoctyl)piperidin-4-yl)methoxy)phenyl)methanone
  参考文献：
  名称：

  Discovery of Selective Menaquinone Biosynthesis Inhibitors against Mycobacterium tuberculosis

  摘要：

  Aurachin RE (1) is a strong antibiotic that was recently found to possess 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) and bacterial electron transport inhibitory activities. Aurachin RE is the only molecule in a series of aurachin natural products that has the chiral center in the alkyl side chain at C9'-position. To identify selective MenA inhibitors against Mycobacterium tuberculosis, a series of chiral molecules were designed based on the structures of previously identified MenA inhibitors and 1. The synthesized molecules were evaluated in in vitro assays, including MenA enzyme and bacterial growth inhibitory assays. We could identify novel MenA inhibitors that showed significant increase in potency of killing nonreplicating M. tuberculosis in the low oxygen recovery assay (LORA) without inhibiting other Gram-positive bacterial growth even at high concentrations. The MenA inhibitors reported here are useful new pharmacophores for the development of selective antimycobacterial agents with strong activity against nonreplicating M. tuberculosis.

  DOI：

  10.1021/jm201608g
• 作为产物：
  描述：

  4-氯-N-甲氧基-N-甲基乙酰胺 在 偶氮二甲酸二异丙酯 、 氢溴酸 、 异丙基氯化镁 、 溶剂黄146 、 三苯基膦 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 43.5h， 生成 tert-butyl 4-((3-(4-chlorobenzoyl)phenoxy)methyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Discovery of Selective Menaquinone Biosynthesis Inhibitors against Mycobacterium tuberculosis

  摘要：

  Aurachin RE (1) is a strong antibiotic that was recently found to possess 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) and bacterial electron transport inhibitory activities. Aurachin RE is the only molecule in a series of aurachin natural products that has the chiral center in the alkyl side chain at C9'-position. To identify selective MenA inhibitors against Mycobacterium tuberculosis, a series of chiral molecules were designed based on the structures of previously identified MenA inhibitors and 1. The synthesized molecules were evaluated in in vitro assays, including MenA enzyme and bacterial growth inhibitory assays. We could identify novel MenA inhibitors that showed significant increase in potency of killing nonreplicating M. tuberculosis in the low oxygen recovery assay (LORA) without inhibiting other Gram-positive bacterial growth even at high concentrations. The MenA inhibitors reported here are useful new pharmacophores for the development of selective antimycobacterial agents with strong activity against nonreplicating M. tuberculosis.

  DOI：

  10.1021/jm201608g

文献信息

• Carboxyboronate as a Versatile In Situ CO Surrogate in Palladium‐Catalyzed Carbonylative Transformations
  作者：Chieh‐Hung Tien、Alina Trofimova、Aleksandra Holownia、Branden S. Kwak、Reed T. Larson、Andrei K. Yudin

  DOI：10.1002/anie.202010211

  日期：2021.2.19

  highlighted in the palladium‐catalyzed aminocarbonylation, alkoxycarbonylation, carbonylative Sonogashira coupling, and carbonylative Suzuki–Miyaura coupling of aryl halides. A variety of amides, esters, (hetero)aromatic ynones, and bis(hetero)aryl ketones were synthesized in good‐to‐excellent yields in a one‐pot fashion.

  羧基-MIDA-硼酸酯的应用（MIDA = N-甲基亚氨基二乙酸）作为各种钯催化转化的原位CO替代物进行了描述。先前曾证明，羧基MIDA硼酸酯是合成硼酸化杂环化合物的长凳稳定的含硼结构单元。本研究表明，羧基-MIDA-硼酸酯除了可用作杂环合成的前体外，它还是一种出色的原位CO替代物，可耐受胺，醇和碳基亲核试剂等反应性功能。在钯催化的氨基羰基化，烷氧基羰基化，羰基化的Sonogashira偶联和芳基卤化物的羰基化的Suzuki-Miyaura偶联中，突出了其广泛的官能团相容性。各种酰胺，酯，（杂）芳族炔酮
• SAR study of piperidine derivatives as inhibitors of 1,4-dihydroxy-2-naphthoate isoprenyltransferase (MenA) from Mycobacterium tuberculosis
  作者：Kaja Berg、Pooja Hegde、Venugopal Pujari、Marzena Brinkmann、David Z. Wilkins、Tanya Parish、Dean C. Crick、Courtney C. Aldrich

  DOI：10.1016/j.ejmech.2023.115125

  日期：2023.3