tert-butyl (2R)-2-[[(1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-6-[(4-methoxyphenyl)methoxycarbonyl]-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-20-(5-pyridin-4-yl-1,2,4-triazol-1-yl)-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-en-21-yl]oxymethyl]-2-methylpyrrolidine-1-carboxylate | 1407975-86-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: tert-butyl (2R)-2-[[(1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-6-[(4-methoxyphenyl)methoxycarbonyl]-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-20-(5-pyridin-4-yl-1,2,4-triazol-1-yl)-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-en-21-yl]oxymethyl]-2-methylpyrrolidine-1-carboxylate
• CAS: 1407975-86-3
• 化学式: C₅₆H₇₉N₅O₇
• 分子量: 934.273
• InChiKey: XRHLSXYYSDVUSN-BMBKKVBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.5
• 重原子数：
  68
• 可旋转键数：
  14
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  tert-butyl (2R)-2-[[(1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-6-[(4-methoxyphenyl)methoxycarbonyl]-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-20-(5-pyridin-4-yl-1,2,4-triazol-1-yl)-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-en-21-yl]oxymethyl]-2-methylpyrrolidine-1-carboxylate 在 苯甲醚 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以90%的产率得到(1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-21-[[(2R)-2-methylpyrrolidin-2-yl]methoxy]-20-(5-pyridin-4-yl-1,2,4-triazol-1-yl)-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-ene-6-carboxylic acid
  参考文献：
  名称：

  Synthesis and biological evaluation of antifungal derivatives of enfumafungin as orally bioavailable inhibitors of β-1,3-glucan synthase

  摘要：

  Orally bioavailable inhibitors of beta-(1,3)-D-glucan synthase have been pursued as new, broad-spectrum fungicidal therapies suitable for treatment in immunocompromised patients. Toward this end, a collaborative medicinal chemistry program was established based on semisynthetic derivatization of the triterpenoid glycoside natural product enfumafungin in order to optimize in vivo antifungal activity and oral absorption properties. In the course of these studies, it was hypothesized that the pharmacokinetic properties of the semisynthetic enfumafungin analog 3 could be improved by tethering the alkyl groups proximal to the basic nitrogen of the C3-aminoether side chain into an azacyclic system, so as to preclude oxidative N-demethylation. The results of this research effort are disclosed herein. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.031
• 作为产物：
  描述：

  (1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-20-acetyloxy-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-21-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-ene-6-carboxylic acid 在 甲醇 、 硫酸 、 三氟化硼乙醚 、 sodium hydride 、 potassium carbonate 、 一水合肼 、 溶剂黄146 作用下， 以 乙醇 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (2R)-2-[[(1R,5S,6R,7R,10R,11R,14R,15S,20R,21R)-6-[(4-methoxyphenyl)methoxycarbonyl]-5,7,10,15-tetramethyl-7-[(2R)-3-methylbutan-2-yl]-20-(5-pyridin-4-yl-1,2,4-triazol-1-yl)-17-oxapentacyclo[13.3.3.01,14.02,11.05,10]henicos-2-en-21-yl]oxymethyl]-2-methylpyrrolidine-1-carboxylate
  参考文献：
  名称：

  Synthesis and biological evaluation of antifungal derivatives of enfumafungin as orally bioavailable inhibitors of β-1,3-glucan synthase

  摘要：

  Orally bioavailable inhibitors of beta-(1,3)-D-glucan synthase have been pursued as new, broad-spectrum fungicidal therapies suitable for treatment in immunocompromised patients. Toward this end, a collaborative medicinal chemistry program was established based on semisynthetic derivatization of the triterpenoid glycoside natural product enfumafungin in order to optimize in vivo antifungal activity and oral absorption properties. In the course of these studies, it was hypothesized that the pharmacokinetic properties of the semisynthetic enfumafungin analog 3 could be improved by tethering the alkyl groups proximal to the basic nitrogen of the C3-aminoether side chain into an azacyclic system, so as to preclude oxidative N-demethylation. The results of this research effort are disclosed herein. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.05.031

文献信息

• Synthesis and biological evaluation of antifungal derivatives of enfumafungin as orally bioavailable inhibitors of β-1,3-glucan synthase
  作者：Brian H. Heasley、Gregory J. Pacofsky、Ahmed Mamai、Hao Liu、Kingsley Nelson、Ghjuvanni Coti、Michael R. Peel、James M. Balkovec、Mark L. Greenlee、Paul Liberator、Dongfang Meng、Dann L. Parker、Robert R. Wilkening、James M. Apgar、F. Racine、Ming Jo Hsu、Robert A. Giacobbe、Jennifer Nielsen Kahn

  DOI：10.1016/j.bmcl.2012.05.031

  日期：2012.11

  Orally bioavailable inhibitors of beta-(1,3)-D-glucan synthase have been pursued as new, broad-spectrum fungicidal therapies suitable for treatment in immunocompromised patients. Toward this end, a collaborative medicinal chemistry program was established based on semisynthetic derivatization of the triterpenoid glycoside natural product enfumafungin in order to optimize in vivo antifungal activity and oral absorption properties. In the course of these studies, it was hypothesized that the pharmacokinetic properties of the semisynthetic enfumafungin analog 3 could be improved by tethering the alkyl groups proximal to the basic nitrogen of the C3-aminoether side chain into an azacyclic system, so as to preclude oxidative N-demethylation. The results of this research effort are disclosed herein. (C) 2012 Elsevier Ltd. All rights reserved.