(1R,2S,3R,7S,11E,13S,15S)-2,15-dihydroxy-3-(2-hydroxyethylsulfanyl)-7-methyl-6-oxabicyclo[11.3.0]hexadec-11-en-5-one | 199739-15-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: (1R,2S,3R,7S,11E,13S,15S)-2,15-dihydroxy-3-(2-hydroxyethylsulfanyl)-7-methyl-6-oxabicyclo[11.3.0]hexadec-11-en-5-one
• CAS: 199739-15-6
• 化学式: C₁₈H₃₀O₅S
• 分子量: 358.499
• InChiKey: UZSYEASYVKGQJD-IBKDDUKYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,2S,3R,7S,11E,13S,15S)-2,15-dihydroxy-3-(2-hydroxyethylsulfanyl)-7-methyl-6-oxabicyclo[11.3.0]hexadec-11-en-5-one 在 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 0.05h， 以62%的产率得到(1R,2S,3R,7S,11E,13S,15S)-2,15-dihydroxy-3-(2-hydroxyethylsulfinyl)-7-methyl-6-oxabicyclo[11.3.0]hexadec-11-en-5-one
  参考文献：
  名称：

  Design and Synthesis of Brefeldin A Sulfide Derivatives as Prodrug Candidates with Enhanced Aqueous Solubilities

  摘要：

  The addition of a variety of thiols to the alpha,beta-unsaturated lactone functionality present in brefeldin A has been carried out, and the resulting sulfides have been oxidized to the corresponding sulfoxides. These sulfoxides have the potential to undergo syn elimination to regenerate brefeldin A. The sulfoxides were more active than the sulfides as cytotoxic agents in a variety of human cancer cell cultures with the activities of the sulfoxides approaching that of brefeldin A itself. The cytotoxicities of the sulfoxides may be due to their conversion back to brefeldin A. The kinetics of sulfoxide elimination to form brefeldin A were studied in four cases, and the results indicate that substantial amounts of brefeldin A are likely to be generated during the cytotoxicity assays of the sulfoxide derivatives. Since the oxidation of sulfides to sulfoxides is a common metabolic reaction, the sulfides derived from brefeldin A can be considered as potential brefeldin A prodrugs. Several of the sulfide derivatives were determined to have enhanced aqueous solubilities relative to brefeldin A itself, A number of brefeldin A succinates, glutarates, oxidation products, and sulfone derivatives were also prepared and evaluated for cytotoxicity in dancer cell cultures. Some of the more active brefeldin A derivatives were tested in an in vivo animal model in which hollow fibers containing cancer cell cultures were implanted subcutaneously (SC) and intraperitoneally (IF), and the compounds were administered IP. Greater cytotoxic activity was observed at the SC site than at the IP site for the majority of these compounds, an observation which is consistent with the hypothesis that they are acting as brefeldin A prodrugs in vivo.

  DOI：

  10.1021/jm970746g
• 作为产物：
  描述：

  布雷非德菌素 A 、 2-巯基乙醇 在 1,8-双二甲氨基萘 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 以93%的产率得到(1R,2S,3R,7S,11E,13S,15S)-2,15-dihydroxy-3-(2-hydroxyethylsulfanyl)-7-methyl-6-oxabicyclo[11.3.0]hexadec-11-en-5-one
  参考文献：
  名称：

  Highly Efficient Diastereoselective Michael Addition of Various Thiols to (+)-Brefeldin A

  摘要：

  The Michael addition of thiols to brefeldin A occurs with high diastereoselectivity, affording ratios of major to minor diastereomers of at least 30:1. On the basis of the X-ray structure of a crystalline dibenzoyl derivative, the major diastereomers are assigned the 3R configuration, while the minor diastereomers have the 3S configuration.

  DOI：

  10.1021/jo971292y

文献信息

• Highly Efficient Diastereoselective Michael Addition of Various Thiols to (+)-Brefeldin A
  作者：Ankush B. Argade、Rudiger D. Haugwitz、Rajesh Devraj、John Kozlowski、Phillip E. Fanwick、Mark Cushman

  DOI：10.1021/jo971292y

  日期：1998.1.1

  The Michael addition of thiols to brefeldin A occurs with high diastereoselectivity, affording ratios of major to minor diastereomers of at least 30:1. On the basis of the X-ray structure of a crystalline dibenzoyl derivative, the major diastereomers are assigned the 3R configuration, while the minor diastereomers have the 3S configuration.
• Design and Synthesis of Brefeldin A Sulfide Derivatives as Prodrug Candidates with Enhanced Aqueous Solubilities
  作者：Ankush B. Argade、Rajesh Devraj、Jeffrey A. Vroman、Rudiger D. Haugwitz、Melinda Hollingshead、Mark Cushman

  DOI：10.1021/jm970746g

  日期：1998.8.1

  The addition of a variety of thiols to the alpha,beta-unsaturated lactone functionality present in brefeldin A has been carried out, and the resulting sulfides have been oxidized to the corresponding sulfoxides. These sulfoxides have the potential to undergo syn elimination to regenerate brefeldin A. The sulfoxides were more active than the sulfides as cytotoxic agents in a variety of human cancer cell cultures with the activities of the sulfoxides approaching that of brefeldin A itself. The cytotoxicities of the sulfoxides may be due to their conversion back to brefeldin A. The kinetics of sulfoxide elimination to form brefeldin A were studied in four cases, and the results indicate that substantial amounts of brefeldin A are likely to be generated during the cytotoxicity assays of the sulfoxide derivatives. Since the oxidation of sulfides to sulfoxides is a common metabolic reaction, the sulfides derived from brefeldin A can be considered as potential brefeldin A prodrugs. Several of the sulfide derivatives were determined to have enhanced aqueous solubilities relative to brefeldin A itself, A number of brefeldin A succinates, glutarates, oxidation products, and sulfone derivatives were also prepared and evaluated for cytotoxicity in dancer cell cultures. Some of the more active brefeldin A derivatives were tested in an in vivo animal model in which hollow fibers containing cancer cell cultures were implanted subcutaneously (SC) and intraperitoneally (IF), and the compounds were administered IP. Greater cytotoxic activity was observed at the SC site than at the IP site for the majority of these compounds, an observation which is consistent with the hypothesis that they are acting as brefeldin A prodrugs in vivo.