methyl (2S)-2-[[(2S,4R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,4R)-2-[[(2R)-4-cyano-2-methylsulfonyloxybutanoyl]amino]-4-methyloctanoyl]-methylamino]-4-methylpentanoyl]amino]-4-methylpentanoyl]-methylamino]-3-(1-methoxyindol-3-yl)propanoyl]amino]-4-methyloctanoyl]-methylamino]propanoate | 1026343-98-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (2S)-2-[[(2S,4R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,4R)-2-[[(2R)-4-cyano-2-methylsulfonyloxybutanoyl]amino]-4-methyloctanoyl]-methylamino]-4-methylpentanoyl]amino]-4-methylpentanoyl]-methylamino]-3-(1-methoxyindol-3-yl)propanoyl]amino]-4-methyloctanoyl]-methylamino]propanoate
• CAS: 1026343-98-5
• 化学式: C₅₅H₉₀N₈O₁₂S
• 分子量: 1087.43
• InChiKey: KLGDWWRVOJPACH-IVUNSTSTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  76
• 可旋转键数：
  35
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  264
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl (2S)-2-[[(2S,4R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,4R)-2-[[(2R)-4-cyano-2-methylsulfonyloxybutanoyl]amino]-4-methyloctanoyl]-methylamino]-4-methylpentanoyl]amino]-4-methylpentanoyl]-methylamino]-3-(1-methoxyindol-3-yl)propanoyl]amino]-4-methyloctanoyl]-methylamino]propanoate 在 锂硼氢 、 乙基硫脲 、 sodium hydride 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 70.0h， 生成 (5S,8S,11S,14S,17S,20S)-14-[(1-methoxyindol-3-yl)methyl]-7,13,19,20-tetramethyl-5,17-bis[(2R)-2-methylhexyl]-8,11-bis(2-methylpropyl)-1-oxa-4,7,10,13,16,19-hexazacyclohenicosane-3,6,9,12,15,18-hexone
  参考文献：
  名称：

  Synthesis of ether analogues derived from HUN-7293 and evaluation as inhibitors of VCAM-1 expression

  摘要：

  The cyclic depsipeptide HUN-7293 (1) and its D-lactate analogue 2 are highly potent inhibitors of inducible cell adhesion molecule expression. We report the synthesis of ether analogues varying in stereochemistry and side chain at the former hydroxyl acid position by employing a 'cut and paste chemistry' methodology starting from 1. As an additional fruit of this synthetic effort, a cyclodepsipeptide featuring a tertiary amine instead of a tertiary amide between PrLEU and MALA was obtained. Results on the inhibitory profile of these compounds in assays of VCAM-1 and ICAM-1 protein expression are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.012
• 作为产物：
  描述：

  HUN-7293 在 N-甲基吗啉 、 sodium hydride 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 methyl (2S)-2-[[(2S,4R)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,4R)-2-[[(2R)-4-cyano-2-methylsulfonyloxybutanoyl]amino]-4-methyloctanoyl]-methylamino]-4-methylpentanoyl]amino]-4-methylpentanoyl]-methylamino]-3-(1-methoxyindol-3-yl)propanoyl]amino]-4-methyloctanoyl]-methylamino]propanoate
  参考文献：
  名称：

  Synthesis of ether analogues derived from HUN-7293 and evaluation as inhibitors of VCAM-1 expression

  摘要：

  The cyclic depsipeptide HUN-7293 (1) and its D-lactate analogue 2 are highly potent inhibitors of inducible cell adhesion molecule expression. We report the synthesis of ether analogues varying in stereochemistry and side chain at the former hydroxyl acid position by employing a 'cut and paste chemistry' methodology starting from 1. As an additional fruit of this synthetic effort, a cyclodepsipeptide featuring a tertiary amine instead of a tertiary amide between PrLEU and MALA was obtained. Results on the inhibitory profile of these compounds in assays of VCAM-1 and ICAM-1 protein expression are discussed. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.012

文献信息

• A Convenient Protocol for Selective Cleavage of 2-Hydroxy Acid Amides. Application to Semisynthesis of the Cyclic Heptapeptide Aza HUN-7293
  作者：Erwin P. Schreiner、Michael Kern、Andrea Steck

  DOI：10.1021/jo025979g

  日期：2002.11.1

  A two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid methyl ester (11) followed by treatment with N-ethylthiourea (13) allows cleavage of 2-hydroxy acid amides under smooth conditions. Successful application of this methodology to the open-chain transesterification product 15 (methylester) of the cyclic heptadepsipeptide HUN-7293, a potent inhibitor of inducible cell adhesion molecule expression, delivered the corresponding hexapeptide 18 with unprotected N-terminus in 70-75% yield. This result demonstrates that the protocol developed even works in the presence of an ester and several methylated and unmethylated amide bonds. Finally, a sequence of ligation of methyl D-dehydroglutaminate (20) to the C-terminus of the saponification product 21, followed by the degradation protocol and ring closure, allowed chemical "point mutation" at the DGCN site affording the aza analogue of HUN-7293 (24) in 15% overall yield. To the best of our knowledge this is the first report on chemoselective cleavage of 2-hydroxy acid amides.
• Synthesis of ether analogues derived from HUN-7293 and evaluation as inhibitors of VCAM-1 expression
  作者：Erwin P. Schreiner、Michael Kern、Andrea Steck、Carolyn A. Foster

  DOI：10.1016/j.bmcl.2004.07.012

  日期：2004.10

  The cyclic depsipeptide HUN-7293 (1) and its D-lactate analogue 2 are highly potent inhibitors of inducible cell adhesion molecule expression. We report the synthesis of ether analogues varying in stereochemistry and side chain at the former hydroxyl acid position by employing a 'cut and paste chemistry' methodology starting from 1. As an additional fruit of this synthetic effort, a cyclodepsipeptide featuring a tertiary amine instead of a tertiary amide between PrLEU and MALA was obtained. Results on the inhibitory profile of these compounds in assays of VCAM-1 and ICAM-1 protein expression are discussed. (C) 2004 Elsevier Ltd. All rights reserved.