(2S,4R)-4-[[2-[(1R,3R)-1-acetyloxy-4-methyl-3-[[(2S,3S)-3-methyl-2-[[(2R)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]-[2-oxo-2-(propan-2-ylamino)ethyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-phenylpentanoic acid | 1303556-48-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (2S,4R)-4-[[2-[(1R,3R)-1-acetyloxy-4-methyl-3-[[(2S,3S)-3-methyl-2-[[(2R)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]-[2-oxo-2-(propan-2-ylamino)ethyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-phenylpentanoic acid
• CAS: 1303556-48-0
• 化学式: C₄₂H₆₄N₆O₈S
• 分子量: 813.072
• InChiKey: SNBACHKZKQNKIB-CAPJTEJHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  57
• 可旋转键数：
  22
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  216
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (R)-Mep-(S)-Ile-OH*HCl 在 吡啶 、 五氟苯酚 、 三氟乙酸 、 lithium hydroxide 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 179.17h， 生成 (2S,4R)-4-[[2-[(1R,3R)-1-acetyloxy-4-methyl-3-[[(2S,3S)-3-methyl-2-[[(2R)-1-methylpiperidine-2-carbonyl]amino]pentanoyl]-[2-oxo-2-(propan-2-ylamino)ethyl]amino]pentyl]-1,3-thiazole-4-carbonyl]amino]-2-methyl-5-phenylpentanoic acid
  参考文献：
  名称：

  The Multiple Multicomponent Approach to Natural Product Mimics: Tubugis, N-Substituted Anticancer Peptides with Picomolar Activity

  摘要：

  The synthesis of a new generation of highly cytotoxic tubulysin analogues (i.e., tubugis) is described. In the key step, the rare, unstable, and synthetically difficult to introduce tertiary amide-N,O-acetal moiety required for high potency in natural tubulysins is replaced by a dipeptoid element formed in an Ugi four-component reaction. Two of the four components required are themselves produced by other multicomponent reactions (MCRs). Thus, the tubugis represent the first examples of the synthesis of natural-product-inspired compounds using three intertwined isonitrile MCRs.

  DOI：

  10.1021/ja2022027

文献信息

• Tubulysin analogues
  申请人：Leibniz-Institut für Pflanzenbiochemie (IPB)

  公开号：EP2409983A1

  公开（公告）日：2012-01-25

  The present invention relates to novel tubulysin compounds (tubulysin analogues) as well as pharmaceutical formulations thereof. The present invention further relates to the use of such compounds for medicinal, agricultural, biotool or cosmetic applications. In particular, the novel tubulysin analogues show a cytostatic effect and can therefore be used for the treatment of proliferative disorders. The tertiary amide moiety of the tubulysin analogues (so-called tubugis) according to the present invention is generated by an Ugi-type reaction.

  本发明涉及新型管胞素化合物（管胞素类似物）及其药物制剂。本发明还涉及此类化合物在医药、农业、生物工具或化妆品方面的应用。特别是，这种新型管胞素类似物具有细胞抑制作用，因此可用于治疗增殖性疾病。根据本发明，管胞素类似物（即所谓的管胞素）的叔酰胺分子是通过 Ugi 型反应生成的。
• TUBULYSIN ANALOGUES
  申请人：Leibniz-Institut für Pflanzenbiochemie (IPB)

  公开号：EP2596008B1

  公开（公告）日：2015-01-14
• Tubulysin Analogues
  申请人：Wessjohann Ludger A.

  公开号：US20130217638A1

  公开（公告）日：2013-08-22

  The present invention relates to novel tubulysin compounds (tubulysin analogues) as well as pharmaceutical formulations thereof. The present invention further relates to the use of such compounds for medicinal, agricultural, biotool or cosmetic applications. In particular, the novel tubulysin analogues show a cytostatic effect and can therefore be used for the treatment of proliferative disorders. The tertiary amide moiety of the tubulysin analogues (so-called tubugis) according to the present invention is generated by an Ugi-type reaction.
• US9371358B2
  申请人：——

  公开号：US9371358B2

  公开（公告）日：2016-06-21
• [EN] TUBULYSIN ANALOGUES<br/>[FR] ANALOGUES DE TUBULYSINE
  申请人：LEIBNIZ INST FUER PFLANZENBIOCHEMIE

  公开号：WO2012010287A1

  公开（公告）日：2012-01-26

  The present invention relates to novel tubulysin compounds (tubulysin analogues) as well as pharmaceutical formulations thereof. The present invention further relates to the use of such compounds for medicinal, agricultural, biotool or cosmetic applications. In particular, the novel tubulysin analogues show a cytostatic effect and can therefore be used for the treatment of proliferative disorders. The tertiary amide moiety of the tubulysin analogues (so-called tubugis) according to the present invention is generated by an Ugi-type reaction.