1,5,9,13-四氮杂环十八烷-6-酮,1,13-二[(2S)-2-甲基-1-羰基丁基]-8-(2Z)-2-十一碳烯-1-基-,(8S)- | 151756-67-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 中文名称: 1,5,9,13-四氮杂环十八烷-6-酮,1,13-二[(2S)-2-甲基-1-羰基丁基]-8-(2Z)-2-十一碳烯-1-基-,(8S)-
• 英文名称: Lipogrammistin-A
• 英文别名: (8S)-1,13-bis[(2S)-2-methylbutanoyl]-8-[(Z)-undec-2-enyl]-1,5,9,13-tetrazacyclooctadecan-6-one
• CAS: 151756-67-1
• 化学式: C₃₅H₆₆N₄O₃
• 分子量: 590.934
• InChiKey: BBWSMYSNDAJELT-BHKVXQOFSA-N

物化性质

• 沸点：
  749.5±60.0 °C(Predicted)
• 密度：
  0.934±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  42
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  碘甲烷-13C 、 1,5,9,13-四氮杂环十八烷-6-酮,1,13-二[(2S)-2-甲基-1-羰基丁基]-8-(2Z)-2-十一碳烯-1-基-,(8S)- 在 potassium hydrogencarbonate 作用下， 以 甲醇 为溶剂， 生成
  参考文献：
  名称：

  Mechanism of hemolysis and erythrocyte transformation caused by lipogrammistin-A, a lipophilic and acylated cyclic polyamine from the skin secretion of soapfishes (Grammistidae)

  摘要：

  The mechanism of hemolysis and erythrocyte transformation caused by lipogrammistin-A (LGA), a lipophilic and acylated cyclic polyamine from the skin secretion of soapfishes (Grammistidae), was investigated. The dependency of hemolysis on the erythrocyte concentration indicated that the amount of membrane-bound LGA required for 50% hemolysis is about 13% of the total phospholipids in erythrocytes on a molar basis. A synthetic analogue which lacked a long alkyl chain exhibited much less activity, suggesting that the alkyl chain is important for membrane-binding. In addition, microscopic observations showed that LGA elicited the invagination of erythrocytes at sublytic concentrations, which makes LGA one of the most potent agents with this transforming activity known to date. Its protonated secondary amino group is responsible for the unequal distribution of LGA in the inner leaflet of the lipid bilayer, which leads to invagination, since acetylation at the amino group markedly reduced the invagination activity. Furthermore, the size of LGA-induced lesions on erythrocyte membrane was estimated to be 7-29 A based on osmotic protection experiments, where the external addition of isotonic molecules in this size range gradually increased the effective dose of LGA. Based on these lines of evidence, the mode of LGA action on erythrocytes is deduced to be as follows. First, LGA molecules bind to erythrocyte membrane by lipophilicity. Second, the molecules accumulate in the inner leaflet of the lipid bilayer by interaction of their cationic ammonium groups with acidic residues of membrane lipid in the inner surface. This uneven distribution of LGA distorts the bilayer structure, and results in a change in cell shape and consequent small lesions. Third, small solutes permeate through the lesions, which induces an osmotic change across the membrane, which leads to colloid-osmotic rupture. This mode of action of LGA on erythrocytes accompanied by cell invagination is the first reported example for natural defense substances.

  DOI：

  10.1016/s0968-0896(99)00128-5
• 作为产物：
  描述：

  N-(2-氰乙基)-1,5-二氨基戊烷 在 platinum(IV) oxide 锂硼氢 、 pyridine-SO3 complex 、 氢气 、 sodium cyanoborohydride 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 氯仿 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 99.33h， 生成 1,5,9,13-四氮杂环十八烷-6-酮,1,13-二[(2S)-2-甲基-1-羰基丁基]-8-(2Z)-2-十一碳烯-1-基-,(8S)-
  参考文献：
  名称：

  Absolute Structure and Total Synthesis of Lipogrammistin-A, a Lipophilic Ichthyotoxin of the Soapfish

  摘要：

  Lipogrammistin-A (Ib) was isolated as an ichthyotoxic and hemolytic constituent of the skin mucus of the grammistid fish Aulacocephalus temmincki. Its absolute stereochemistry was established by chemical degradation and total synthesis. The stereochemistry of the 2-methylbutyryl moieties attached to N9 and N15 was determined to be S by HPLC analysis of a diastereomeric derivative. The stereochemistry of the remaining C4 position was elucidated to be S by a total synthesis of the two diastereomers (4S)- and (4R)-1.

  DOI：

  10.1021/jo9722461

文献信息

• Fujiwara; Kan; Fukuyama, Synlett, 2000, # 11, p. 1667 - 1669
  作者：Fujiwara、Kan、Fukuyama

  DOI：——

  日期：——
• Efficient macrocyclization by means of 2-nitrobenzenesulfonamide and total synthesis of lipogrammistin-A
  作者：Toshiyuki Kan、Akiko Fujiwara、Hideki Kobayashi、Tohru Fukuyama

  DOI：10.1016/s0040-4020(02)00626-9

  日期：2002.8

  Synthesis of medium- and large-sized cyclic amines using alkylation with 2-nitrobenzenesulfonamides is described. Using either conventional alkylation procedures or Mitsunobu conditions, the cyclization reaction proceeded in a highly efficient manner. The usefulness of this methodology has been fully demonstrated in the total synthesis of lipogrammistin-A (9), an 18-membered cyclic polyamine. (C) 2002 Published by Elsevier Science Ltd.
• Mechanism of hemolysis and erythrocyte transformation caused by lipogrammistin-A, a lipophilic and acylated cyclic polyamine from the skin secretion of soapfishes (Grammistidae)
  作者：Yoshimasa Kobayashi、Hiroyuki Onuki、Kazuo Tachibana

  DOI：10.1016/s0968-0896(99)00128-5

  日期：1999.9

  The mechanism of hemolysis and erythrocyte transformation caused by lipogrammistin-A (LGA), a lipophilic and acylated cyclic polyamine from the skin secretion of soapfishes (Grammistidae), was investigated. The dependency of hemolysis on the erythrocyte concentration indicated that the amount of membrane-bound LGA required for 50% hemolysis is about 13% of the total phospholipids in erythrocytes on a molar basis. A synthetic analogue which lacked a long alkyl chain exhibited much less activity, suggesting that the alkyl chain is important for membrane-binding. In addition, microscopic observations showed that LGA elicited the invagination of erythrocytes at sublytic concentrations, which makes LGA one of the most potent agents with this transforming activity known to date. Its protonated secondary amino group is responsible for the unequal distribution of LGA in the inner leaflet of the lipid bilayer, which leads to invagination, since acetylation at the amino group markedly reduced the invagination activity. Furthermore, the size of LGA-induced lesions on erythrocyte membrane was estimated to be 7-29 A based on osmotic protection experiments, where the external addition of isotonic molecules in this size range gradually increased the effective dose of LGA. Based on these lines of evidence, the mode of LGA action on erythrocytes is deduced to be as follows. First, LGA molecules bind to erythrocyte membrane by lipophilicity. Second, the molecules accumulate in the inner leaflet of the lipid bilayer by interaction of their cationic ammonium groups with acidic residues of membrane lipid in the inner surface. This uneven distribution of LGA distorts the bilayer structure, and results in a change in cell shape and consequent small lesions. Third, small solutes permeate through the lesions, which induces an osmotic change across the membrane, which leads to colloid-osmotic rupture. This mode of action of LGA on erythrocytes accompanied by cell invagination is the first reported example for natural defense substances.
• Absolute Structure and Total Synthesis of Lipogrammistin-A, a Lipophilic Ichthyotoxin of the Soapfish
  作者：Hiroyuki Onuki、Kei Ito、Yoshimasa Kobayashi、Nobuaki Matsumori、Kazuo Tachibana、Nobuhiro Fusetani

  DOI：10.1021/jo9722461

  日期：1998.6.1

  Lipogrammistin-A (Ib) was isolated as an ichthyotoxic and hemolytic constituent of the skin mucus of the grammistid fish Aulacocephalus temmincki. Its absolute stereochemistry was established by chemical degradation and total synthesis. The stereochemistry of the 2-methylbutyryl moieties attached to N9 and N15 was determined to be S by HPLC analysis of a diastereomeric derivative. The stereochemistry of the remaining C4 position was elucidated to be S by a total synthesis of the two diastereomers (4S)- and (4R)-1.