(3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methylpropyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone | 154491-55-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methylpropyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
• 英文别名: beauveriolide I；beauverolide I；epothilone B
• CAS: 154491-55-1
• 化学式: C₂₇H₄₁N₃O₅
• 分子量: 487.64
• InChiKey: ZKSLFHXTWGEITF-JIORRVSTSA-N

物化性质

• 熔点：
  242-244 °C(Solv: methanol (67-56-1))
• 沸点：
  777.6±60.0 °C(Predicted)
• 密度：
  1.044±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  甲醇 、 (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methylpropyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone 在 potassium carbonate 作用下， 反应 24.0h， 以2.2 mg的产率得到
  参考文献：
  名称：

  生物活性环缩肽的结构，白僵菌 I 和 II，昆虫病原真菌白僵菌的代谢物。

  摘要：

  在环缩肽中，白僵菌 I (1) 和 II (2) 已从白僵菌菌丝体中分离出来，并且通过光谱分析以及相应 3-羟基辛酸衍生物的合成阐明了它们的立体结构。Beauveriolide I (1) 对斜纹夜蛾和 Callosobruchus chinensis 表现出中等杀虫活性。

  DOI：

  10.1246/bcsj.66.3041
• 作为产物：
  描述：

  (3S,4S)-4-nitrobenzyl 3-hydroxy-4-methyl octanoate 在 palladium on activated charcoal 盐酸 、 4-二甲氨基吡啶 、 N-羟基丁二酰亚胺 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 、 乙腈 为溶剂， 反应 4.0h， 生成 (3R,6S,9S,13S)-9-benzyl-13-[(2S)-hexan-2-yl]-6-methyl-3-(2-methylpropyl)-1-oxa-4,7,10-triazacyclotridecane-2,5,8,11-tetrone
  参考文献：
  名称：

  Total synthesis of beauveriolide I

  摘要：

  The first total synthesis of beauveriolide I (1a), a selective ACAT inhibitor, is described. The key steps in this synthesis involved a diastercoselective aldol condensation sequence and a macrocyclization. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.09.188

文献信息

• METHOD FOR SELECTIVELY INHIBITING ACAT1 IN THE TREATMENT OF ALZHEIMER'S DISEASE
  申请人：Trustees of Dartmouth College

  公开号：US20140044757A1

  公开（公告）日：2014-02-13

  The present invention features methods for stimulating clearance of amyloid beta in microglia, decreasing cognitive decline associated with amyloid pathology, and treating Alzheimer's disease by selectively inhibiting the expression or activity of Acyl-CoA:Cholesterol Acyltransferase 1, but not Acyl-CoA:Cholesterol Acyltransferase 2.
• METHOD FOR SELECTIVELY INHIBITING ACAT1 IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Trustees of Dartmouth College

  公开号：US20140308340A1

  公开（公告）日：2014-10-16

  The present invention features methods for stimulating clearance of misfolded or aggregated proteins or peptides in microglia, and treating neurodegenerative diseases associated with such pathology in brain by selectively inhibiting the expression or activity of Acyl-CoA:Cholesterol Acyltransferase 1, but not Acyl-CoA:Cholesterol Acyltransferase 2.
• METHOD FOR SELECTIVELY INHIBITING ACAT1 IN THE TREATMENT OF OBESITY, METABOLIC SYNDROME, AND ATHEROSCLEROSIS
  申请人：Trustees of Dartmouth College

  公开号：US20160355824A1

  公开（公告）日：2016-12-08

  The present invention features methods for preventing and treating three related diseases, diet-induced obesity, metabolic syndrome, and atherosclerosis, alone or in combination by inhibiting Acyl-CoA: Cholesterol Acyltransferase 1 (ACATI) activity or expression in myeloid cells.
• Combination of ACAT1 Inhibitor and Checkpoint Antibody for Treating Cancer
  申请人：Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

  公开号：US20190015507A1

  公开（公告）日：2019-01-17

  The present disclosure provides methods and compositions for the treatment of cancer using an ACAT1 inhibitor in combination with an immune checkpoint inhibitor. The immune checkpoint inhibitor may inhibit the programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), lymphocyte-activation protein 3 (LAG-3), or combinations thereof. The ACAT1 inhibitor may be avasimibe, pactimibe, or purpactins, without limitation.
• US9149492B2
  申请人：——

  公开号：US9149492B2

  公开（公告）日：2015-10-06