[(2S,4aS,7S,8R,8aR)-7-[5-[4-(cyclopropanecarbonyloxy)phenyl]-4-hydroxy-2-oxo-1H-pyridine-3-carbonyl]-5-methyl-8-[(E)-prop-1-enyl]-1,2,3,4,4a,7,8,8a-octahydronaphthalen-2-yl]methyl cyclopropanecarboxylate | 1432134-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: [(2S,4aS,7S,8R,8aR)-7-[5-[4-(cyclopropanecarbonyloxy)phenyl]-4-hydroxy-2-oxo-1H-pyridine-3-carbonyl]-5-methyl-8-[(E)-prop-1-enyl]-1,2,3,4,4a,7,8,8a-octahydronaphthalen-2-yl]methyl cyclopropanecarboxylate
• CAS: 1432134-55-8
• 化学式: C₃₅H₃₉NO₇
• 分子量: 585.697
• InChiKey: ICHAALFXLAGUNM-ALDFNOARSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.49
• 拓扑面积：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  [(2S,4aS,7S,8R,8aR)-7-[5-[4-(cyclopropanecarbonyloxy)phenyl]-4-hydroxy-2-oxo-1H-pyridine-3-carbonyl]-5-methyl-8-[(E)-prop-1-enyl]-1,2,3,4,4a,7,8,8a-octahydronaphthalen-2-yl]methyl cyclopropanecarboxylate 在 甲醇 、 lithium hydroxide 作用下， 生成 [4-[5-[(1R,2S,4aS,7S,8aR)-7-(hydroxymethyl)-4-methyl-1-[(E)-prop-1-enyl]-1,2,4a,5,6,7,8,8a-octahydronaphthalene-2-carbonyl]-4-hydroxy-6-oxo-1H-pyridin-3-yl]phenyl] cyclopropanecarboxylate
  参考文献：
  名称：

  Structure–activity relationship of cytochrome bc1 reductase inhibitor broad spectrum antifungal ilicicolin H

  摘要：

  Ilicicolin H is a broad spectrum antifungal agent showing sub micro g/mL MICs against Candida spp., Aspergillus fumigatus and Cryptococcus spp. It is a potent inhibitor (C-50 2-3 ng/mL) of the mitochondrial cytochrome bc1 reductase with over 1000-fold selectivity against rat liver cytochrome bc1 reductase. Structure-activity relationship of semisynthetic derivatives by chemical modification of ilicicolin H and its 19-hydroxy derivative produced by biotransformation have been described. Basic 4'-esters and moderately polar N- and O-alkyl derivatives retained antifungal and the cytochrome bc1 reductase activities. 4',19-Diacetate and 19-cyclopropyl acetate retained antifungal and enzyme activity and selectivity with over 20-fold improvement of plasma protein binding. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.023
• 作为产物：
  描述：

  [(2S,4aS,7S,8R,8aR)-7-[4-hydroxy-5-(4-hydroxyphenyl)-2-oxo-1H-pyridine-3-carbonyl]-5-methyl-8-[(E)-prop-1-enyl]-1,2,3,4,4a,7,8,8a-octahydronaphthalen-2-yl]methyl acetate 、 环丙甲酸 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 生成 [4-[5-[(1R,2S,4aS,7S,8aR)-7-(hydroxymethyl)-4-methyl-1-[(E)-prop-1-enyl]-1,2,4a,5,6,7,8,8a-octahydronaphthalene-2-carbonyl]-4-hydroxy-6-oxo-1H-pyridin-3-yl]phenyl] cyclopropanecarboxylate 、 [(2S,4aS,7S,8R,8aR)-7-[5-[4-(cyclopropanecarbonyloxy)phenyl]-4-hydroxy-2-oxo-1H-pyridine-3-carbonyl]-5-methyl-8-[(E)-prop-1-enyl]-1,2,3,4,4a,7,8,8a-octahydronaphthalen-2-yl]methyl cyclopropanecarboxylate 、 [(2S,4aS,7S,8R,8aR)-7-[4-hydroxy-5-(4-hydroxyphenyl)-2-oxo-1H-pyridine-3-carbonyl]-5-methyl-8-[(E)-prop-1-enyl]-1,2,3,4,4a,7,8,8a-octahydronaphthalen-2-yl]methyl cyclopropanecarboxylate
  参考文献：
  名称：

  Structure–activity relationship of cytochrome bc1 reductase inhibitor broad spectrum antifungal ilicicolin H

  摘要：

  Ilicicolin H is a broad spectrum antifungal agent showing sub micro g/mL MICs against Candida spp., Aspergillus fumigatus and Cryptococcus spp. It is a potent inhibitor (C-50 2-3 ng/mL) of the mitochondrial cytochrome bc1 reductase with over 1000-fold selectivity against rat liver cytochrome bc1 reductase. Structure-activity relationship of semisynthetic derivatives by chemical modification of ilicicolin H and its 19-hydroxy derivative produced by biotransformation have been described. Basic 4'-esters and moderately polar N- and O-alkyl derivatives retained antifungal and the cytochrome bc1 reductase activities. 4',19-Diacetate and 19-cyclopropyl acetate retained antifungal and enzyme activity and selectivity with over 20-fold improvement of plasma protein binding. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.023

文献信息

• Structure–activity relationship of cytochrome bc1 reductase inhibitor broad spectrum antifungal ilicicolin H
  作者：Sheo B. Singh、Weiguo Liu、Xiaohua Li、Tom Chen、Ali Shafiee、Sarah Dreikorn、Viktor Hornak、Maria Meinz、Janet C. Onishi

  DOI：10.1016/j.bmcl.2013.03.023

  日期：2013.5

  Ilicicolin H is a broad spectrum antifungal agent showing sub micro g/mL MICs against Candida spp., Aspergillus fumigatus and Cryptococcus spp. It is a potent inhibitor (C-50 2-3 ng/mL) of the mitochondrial cytochrome bc1 reductase with over 1000-fold selectivity against rat liver cytochrome bc1 reductase. Structure-activity relationship of semisynthetic derivatives by chemical modification of ilicicolin H and its 19-hydroxy derivative produced by biotransformation have been described. Basic 4'-esters and moderately polar N- and O-alkyl derivatives retained antifungal and the cytochrome bc1 reductase activities. 4',19-Diacetate and 19-cyclopropyl acetate retained antifungal and enzyme activity and selectivity with over 20-fold improvement of plasma protein binding. (C) 2013 Elsevier Ltd. All rights reserved.