(1-Acetyloxy-6-oxohexyl) acetate | 143379-25-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (1-Acetyloxy-6-oxohexyl) acetate
• CAS: 143379-25-3
• 化学式: C₁₀H₁₆O₅
• 分子量: 216.234
• InChiKey: OOFGSQDFXTUTIJ-UHFFFAOYSA-N

物化性质

• 沸点：
  303.0±32.0 °C(Predicted)
• 密度：
  1.090±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1-Acetyloxy-6-oxohexyl) acetate 在 potassium fluoride 、 lithium aluminium tetrahydride 、 四氯化锡 、 dipyridine chromium trioxide 、 N,N'-二环己基碳二亚胺 、 copper(l) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 2.25h， 生成 rel-(1R,4aS,8aS)-1-methyl-4a,5,6,7,8,8a-hexahydro-1H-2,3-benzoxazine-3-oxide
  参考文献：
  名称：

  硝基烯烃与烯烃的分子内 [4 + 2] 环加成反应

  摘要：

  Cycloadditions 立体选择性分子内存在 de SnCl 4 de nitro-1 nonadiene-1,7 et de nitro-2 decadiene-2,8: 获得 d'oxydes-3 d'hexahydro-4a,5,6,7,8,8a benzooxazines -2,3

  DOI：

  10.1021/ja00266a036
• 作为产物：
  描述：

  Acetic acid 1-acetoxy-hept-6-enyl ester 在 二甲基硫 、 臭氧 作用下， 生成 (1-Acetyloxy-6-oxohexyl) acetate
  参考文献：
  名称：

  Intensely Potent Doxorubicin Analogues:  Structure−Activity Relationship

  摘要：

  N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin analogue that retains full potency against tumor cells that express elevated levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1-yl)doxorubicin, an aldehyde capable of existing in equilibrium with a cyclic carbinolamine. To investigate the structural determinants of potency for 1b, we have prepared a series of chemically related compounds in which various omega-[bis(acetoxy)]alkyl or omega-[bis(acetoxy)]alkoxyalkyl groups are substituted at the 3'-amino position of the daunosamine sugar. These groups were selected to assess the effect of chain length, oxygen substitution, and carbinolamine ring size on analogue potency. The compounds were evaluated for their ability to inhibit the in vitro growth of the following cell lines: (a) Chinese hamster ovary (CHO) cells, (b) a CHO cell mutant 100-fold resistant to doxorubicin that expresses elevated levels of P-glycoprotein, (c) a murine ductal cell pancreatic adenocarcinoma (Pane 02), and (d) a murine mammary carcinoma (CA 755). The most potent members of the series were those that could form a straight chain aldehyde intermediate after esterase-mediated hydrolysis of the omega-bis(acetoxy) groups and give rise to 5- or 6-membered ring carbinolamines. Analogues capable of forming 7-, 8-, or 9-membered carbinolamines were markedly less active. The N-methyl derivative of 1b, which cannot give rise to a cyclic carbinolamine, was 2 orders of magnitude less potent than 1b. A branched chain analogue, If, which contained a tertiary carbon atom adjacent to the omega-bis(acetoxy) groups, was also substantially less active than its nonbranched counterpart, 1a. These findings suggest that the chain length of the 3'-amino substituents and the ability of the derived aldehydes to form 5- or 6-membered carbinolamines are critical determinants of biologic potency.

  DOI：

  10.1021/jm9706980

文献信息

• Intensely Potent Doxorubicin Analogues:  Structure−Activity Relationship
  作者：David Farquhar、Abdallah Cherif、Elena Bakina、J. Arly Nelson

  DOI：10.1021/jm9706980

  日期：1998.3.1

  N-(5,5-Diacetoxypent-1-yl)doxorubicin (1b) is an intensely cytotoxic doxorubicin analogue that retains full potency against tumor cells that express elevated levels of P-glycoprotein and are resistant to doxorubicin. 1b was designed to be hydrolyzed in the presence of carboxylate esterases to N-(5-oxypent-1-yl)doxorubicin, an aldehyde capable of existing in equilibrium with a cyclic carbinolamine. To investigate the structural determinants of potency for 1b, we have prepared a series of chemically related compounds in which various omega-[bis(acetoxy)]alkyl or omega-[bis(acetoxy)]alkoxyalkyl groups are substituted at the 3'-amino position of the daunosamine sugar. These groups were selected to assess the effect of chain length, oxygen substitution, and carbinolamine ring size on analogue potency. The compounds were evaluated for their ability to inhibit the in vitro growth of the following cell lines: (a) Chinese hamster ovary (CHO) cells, (b) a CHO cell mutant 100-fold resistant to doxorubicin that expresses elevated levels of P-glycoprotein, (c) a murine ductal cell pancreatic adenocarcinoma (Pane 02), and (d) a murine mammary carcinoma (CA 755). The most potent members of the series were those that could form a straight chain aldehyde intermediate after esterase-mediated hydrolysis of the omega-bis(acetoxy) groups and give rise to 5- or 6-membered ring carbinolamines. Analogues capable of forming 7-, 8-, or 9-membered carbinolamines were markedly less active. The N-methyl derivative of 1b, which cannot give rise to a cyclic carbinolamine, was 2 orders of magnitude less potent than 1b. A branched chain analogue, If, which contained a tertiary carbon atom adjacent to the omega-bis(acetoxy) groups, was also substantially less active than its nonbranched counterpart, 1a. These findings suggest that the chain length of the 3'-amino substituents and the ability of the derived aldehydes to form 5- or 6-membered carbinolamines are critical determinants of biologic potency.
• Intramolecular [4 + 2] cycloadditions of nitroalkenes with olefins
  作者：Scott E. Denmark、Michael S. Dappen、Christopher J. Cramer

  DOI：10.1021/ja00266a036

  日期：1986.3

  Cycloadditions stereoselectives intramoleculaires en presence de SnCl 4 de nitro-1 nonadiene-1,7 et de nitro-2 decadiene-2,8: obtention d'oxydes-3 d'hexahydro-4a,5,6,7,8,8a benzooxazines-2,3

  Cycloadditions 立体选择性分子内存在 de SnCl 4 de nitro-1 nonadiene-1,7 et de nitro-2 decadiene-2,8: 获得 d'oxydes-3 d'hexahydro-4a,5,6,7,8,8a benzooxazines -2,3