iso-migrastatin

• 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: iso-migrastatin
• 英文别名: Isomigrastatin；iso-MGS；4-[(5S)-7-[(2R,3S,4S,5S)-4-hydroxy-5-methoxy-3-methyl-12-oxo-1-oxacyclododeca-6,10-dien-2-yl]-5-methyl-4-oxooct-6-enyl]piperidine-2,6-dione
• 化学式: C₂₇H₃₉NO₇
• 分子量: 489.609
• InChiKey: TYTDEHCAAKKYOG-PJSZUTIQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  35
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.63
• 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：

  iso-migrastatin 在 Stryker's reagent 作用下， 以 水 、 苯 为溶剂， 反应 2.0h， 以22.1 mg的产率得到2,3-dihydro-isomigrastatin
  参考文献：
  名称：

  Lactimidomycin, Iso-migrastatin and Related Glutarimide-Containing 12-Membered Macrolides Are Extremely Potent Inhibitors of Cell Migration

  摘要：

  Migrastatin (1), iso-migrastatin (5) and lactimidomycin (7) are all glutarimide-containing polyketides known for their unique structures and cytotoxic activities against human cancer cell lines. Migrastatin, a strong inhibitor of tumor cell migration, has been an important lead in the development of antimetastatic agents. Yet studies of the related 12-membered macrolides iso-migrastatin, lactimidomycin, and related analogues have been hampered by their limited availability. We report here the production, isolation, structural characterization, and biological activities of iso-migrastatin, lactimidomycin, and 23 related congeners. Our studies showed that, as a family, the glutarimide-containing 12-membered macrolides are extremely potent cell migration inhibitors with some members displaying activity on par or superior to that of migrastatin as exemplified by compounds 5, 7, and 9-12. On the basis of these findings, the structures and activity of this family of compounds as cell migration inhibitors are discussed.

  DOI：

  10.1021/ja808462p
• 作为产物：
  描述：

  3-(甲酰基甲基)戊二酰亚胺 在 咪唑 、 sodium tetrahydroborate 、 [(1,2-bis(diphenylphosphino)benzene)CuH] 、 (4R)-4-(1H-indol-3-ylmethyl)-3-(4-methylphenyl)sulfonyl-2-phenyl-1,3,2-oxazaborolidin-5-one 、 碘 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 62.0h， 生成 iso-migrastatin
  参考文献：
  名称：

  拉米霉素，异司他抑素和同类戊二酰亚胺抗生素的总合成和生物学评估

  摘要：

  乳单霉素（1）在文献中被描述为一种非常有效的细胞迁移抑制剂。受此主张的鼓舞，我们开发了一种简洁，可扩展的二方戊二酰亚胺-大环内酯抗生素合成方法，该方法依靠闭环炔烃复分解（RCAM）的作用来形成异常紧张的12元头基。随后从成功途径到1的故意偏离，也带来了姊妹化合物异米格拉他汀（2）以及这些大环内酯类药物的一系列非天然类似物。对该化合物收集物进行的仔细生物学重新评估显示1即使在化合物暴露一天后，子代对一组癌细胞仍具有强大的细胞毒性；因此，对肿瘤细胞迁移的任何潜在特异性作用与细胞死亡的急性作用是无法区分的。在亚毒性剂量下未观察到明显的细胞迁移抑制作用。尽管这些发现不能与文献中的某些报道相吻合，但它们与乳嘧啶霉素主要是核糖体结合剂这一观念相符，能够在翻译阶段有效地终止蛋白质的生物合成。

  DOI：

  10.1002/chem.201300393

文献信息

• Total Syntheses and Biological Reassessment of Lactimidomycin, Isomigrastatin and Congener Glutarimide Antibiotics
  作者：Kévin Micoine、Peter Persich、Josep Llaveria、My-Hanh Lam、Andreas Maderna、Frank Loganzo、Alois Fürstner

  DOI：10.1002/chem.201300393

  日期：2013.6.3

  Lactimidomycin (1) was described in the literature as an exquisitely potent cell migration inhibitor. Encouraged by this claim, we developed a concise and scalable synthesis of this bipartite glutarimide‐macrolide antibiotic, which relies on the power of ring‐closing alkyne metathesis (RCAM) for the formation of the unusually strained 12‐membered head group. Subsequent deliberate digression from the

  乳单霉素（1）在文献中被描述为一种非常有效的细胞迁移抑制剂。受此主张的鼓舞，我们开发了一种简洁，可扩展的二方戊二酰亚胺-大环内酯抗生素合成方法，该方法依靠闭环炔烃复分解（RCAM）的作用来形成异常紧张的12元头基。随后从成功途径到1的故意偏离，也带来了姊妹化合物异米格拉他汀（2）以及这些大环内酯类药物的一系列非天然类似物。对该化合物收集物进行的仔细生物学重新评估显示1即使在化合物暴露一天后，子代对一组癌细胞仍具有强大的细胞毒性；因此，对肿瘤细胞迁移的任何潜在特异性作用与细胞死亡的急性作用是无法区分的。在亚毒性剂量下未观察到明显的细胞迁移抑制作用。尽管这些发现不能与文献中的某些报道相吻合，但它们与乳嘧啶霉素主要是核糖体结合剂这一观念相符，能够在翻译阶段有效地终止蛋白质的生物合成。
• Lactimidomycin, Iso-migrastatin and Related Glutarimide-Containing 12-Membered Macrolides Are Extremely Potent Inhibitors of Cell Migration
  作者：Jianhua Ju、Scott R. Rajski、Si-Kyu Lim、Jeong-Woo Seo、Noël R. Peters、F. Michael Hoffmann、Ben Shen

  DOI：10.1021/ja808462p

  日期：2009.2.4

  Migrastatin (1), iso-migrastatin (5) and lactimidomycin (7) are all glutarimide-containing polyketides known for their unique structures and cytotoxic activities against human cancer cell lines. Migrastatin, a strong inhibitor of tumor cell migration, has been an important lead in the development of antimetastatic agents. Yet studies of the related 12-membered macrolides iso-migrastatin, lactimidomycin, and related analogues have been hampered by their limited availability. We report here the production, isolation, structural characterization, and biological activities of iso-migrastatin, lactimidomycin, and 23 related congeners. Our studies showed that, as a family, the glutarimide-containing 12-membered macrolides are extremely potent cell migration inhibitors with some members displaying activity on par or superior to that of migrastatin as exemplified by compounds 5, 7, and 9-12. On the basis of these findings, the structures and activity of this family of compounds as cell migration inhibitors are discussed.