cyclo(-L-Orn-L-Thr-L-Ala-L-Asn-D-Asn-D-Leu-L-Thr-D-Leu-D-Ada-) | 647014-71-9

• 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: cyclo(-L-Orn-L-Thr-L-Ala-L-Asn-D-Asn-D-Leu-L-Thr-D-Leu-D-Ada-)
• 英文别名: cyclo-L-Thr-L-Ala-L-Asn-D-Asn-D-Leu-L-Thr-D-Leu-D-Ada-L-Orn；cyclo[Ala-Asn-D-Asn-D-Leu-Thr-D-Leu-D-Nle(Bu)(Bu)-Orn-Thr]；2-[(2S,5R,8R,11S,14R,17R,20S,23S,26S)-5-(2-amino-2-oxoethyl)-20-(3-aminopropyl)-11,23-bis[(1R)-1-hydroxyethyl]-26-methyl-8,14-bis(2-methylpropyl)-17-octyl-3,6,9,12,15,18,21,24,27-nonaoxo-1,4,7,10,13,16,19,22,25-nonazacycloheptacos-2-yl]acetamide
• CAS: 647014-71-9
• 化学式: C₄₆H₈₂N₁₂O₁₃
• 分子量: 1011.23
• InChiKey: SGWFVRXAMBMUCN-GPTNCURJSA-N

物化性质

• 沸点：
  1470.5±65.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  71
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  415
• 氢给体数：
  14
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (S)-7-butyryloxy-5-chloro-3-(3-hydroxypropyl)-7-methyl-6H-isochromene-6,8-dione 、 cyclo(-L-Orn-L-Thr-L-Ala-L-Asn-D-Asn-D-Leu-L-Thr-D-Leu-D-Ada-) 在 N-溴代丁二酰亚胺(NBS) 、 碳酸氢钠 、 silver(l) oxide 作用下， 以 乙腈 为溶剂， 反应 73.0h， 以5 mg的产率得到[(3S,4R,7S)-2-[3-[(2S,5S,8S,11S,14R,17R,20S,23R,26R)-11,14-bis(2-amino-2-oxoethyl)-5,20-bis[(1R)-1-hydroxyethyl]-8-methyl-17,23-bis(2-methylpropyl)-26-octyl-3,6,9,12,15,18,21,24,27-nonaoxo-1,4,7,10,13,16,19,22,25-nonazacycloheptacos-2-yl]propyl]-5-chloro-4-hydroxy-7-methyl-6,8-dioxospiro[4H-isoquinoline-3,2'-oxolane]-7-yl] butanoate
  参考文献：
  名称：

  氯褐菌素的全合成、绝对立体化学的分配和结构修正

  摘要：

  氯熔菌素的第一次全合成以收敛方式完成。以所有四种明确的非对映体模型发色团作为参考，通过 1 H NMR 研究和不对称合成确定并修正为 (4S,8R,9S) 的绝对立体化学为 (4S,8R,9S)。这使得首次确定了天然氯熔菌素的完整结构。对映选择性铜介导的 4 氧化、azaphilone 2 与含游离胺的环肽 3 的温和偶联以及最终螺胺形成的一锅三步方案均成功高效实现，以产生正确的立体化学产品1a.

  DOI：

  10.1021/ja072225g
• 作为产物：
  描述：

  cyclo[Ala-Asn(Trt)(Trt)-D-Asn(Trt)(Trt)-D-Leu-Thr-D-Leu-D-Nle(Bu)(Bu)-Orn-Thr] 在 三异丙基硅烷 、 水 、 三氟乙酸 作用下， 反应 3.0h， 以6 mg的产率得到cyclo(-L-Orn-L-Thr-L-Ala-L-Asn-D-Asn-D-Leu-L-Thr-D-Leu-D-Ada-)
  参考文献：
  名称：

  Synthesis of the cyclic nonapeptide of chlorofusin using a convergent [3+3+3]-fragment coupling strategy

  摘要：

  A [3+3+3]-fragment coupling strategy was successfully applied in the synthesis of the nonacyclopeptide of chlorofusin, a potent natural antagonist against p53-MDM2 interactions. The accomplished convergent synthesis includes parallel syntheses of three tripeptides and their sequential assembly, and macrocyclization of the linear precursor to the required 27-membered nonacyclopeptide. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2010.03.032

文献信息

• Mori, Tomonori; Miyagi, Marie; Suzuki, Kengo, Heterocycles, 2007, vol. 72, p. 275 - 291
  作者：Mori, Tomonori、Miyagi, Marie、Suzuki, Kengo、Shibasaki, Mitsuhito、Saikawa, Yoko、Nakata, Masaya

  DOI：——

  日期：——
• Solid-Phase Synthesis of the Cyclic Peptide Portion of Chlorofusin, an Inhibitor of p53-MDM2 Interactions
  作者：John P. Malkinson、Mire Zloh、Mohanad Kadom、Rachel Errington、Paul J. Smith、Mark Searcey

  DOI：10.1021/ol0360849

  日期：2003.12.1

  [GRAPHICS]The first solid-phase synthesis of the chlorofusin peptide is described. The synthesis involved side-chain immobilization of N-alpha-Fmoc-Asp-ODmab. Synthesis of the linear peptide, initially incorporating racemic Ade8 and unsubstituted ornithine in place of the chromophore-bearing residue, was followed by cyclization on resin and peptide release to give a mixture of diastereomers. Resynthesis identified (by HPLC) the second isomer as analogous to the natural product. Initial biological assays, using an immunofluorescence method, suggest that the compounds are not cytotoxic but do not inhibit the p53/mdm2 interaction.
• Synthesis of the chlorofusin cyclic peptide
  作者：Sang Yeul Lee、Dale L. Boger

  DOI：10.1016/j.tet.2008.09.029

  日期：2009.4

  An efficient and convergent solution-phase synthesis of the cyclic peptide of the natural product chlorofusin, a reported inhibitor of the MDM2-p53 interaction, is detailed. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis of the cyclic nonapeptide of chlorofusin using a convergent [3+3+3]-fragment coupling strategy
  作者：Yan-Li Wang、Wen-Jian Qian、Wan-Guo Wei、Yue Zhang、Zhu-Jun Yao

  DOI：10.1016/j.tet.2010.03.032

  日期：2010.5

  A [3+3+3]-fragment coupling strategy was successfully applied in the synthesis of the nonacyclopeptide of chlorofusin, a potent natural antagonist against p53-MDM2 interactions. The accomplished convergent synthesis includes parallel syntheses of three tripeptides and their sequential assembly, and macrocyclization of the linear precursor to the required 27-membered nonacyclopeptide. (C) 2010 Elsevier Ltd. All rights reserved.
• Total Synthesis, Assignment of Absolute Stereochemistry, and Structural Revision of Chlorofusin
  作者：Wen-Jian Qian、Wan-Guo Wei、Yong-Xia Zhang、Zhu-Jun Yao

  DOI：10.1021/ja072225g

  日期：2007.5.1

  The first total synthesis of chlorofusin was accomplished in a convergent fashion. With all four unambiguous diastereomeric model chromophores as references, the absolute stereochemistry of the chlorofusin chromophore was determined and revised to be (4S,8R,9S) by 1H NMR studies and asymmetric synthesis. This allows the complete structure of natural chlorofusin to be assigned for the first time. Enantioselective

  氯熔菌素的第一次全合成以收敛方式完成。以所有四种明确的非对映体模型发色团作为参考，通过 1 H NMR 研究和不对称合成确定并修正为 (4S,8R,9S) 的绝对立体化学为 (4S,8R,9S)。这使得首次确定了天然氯熔菌素的完整结构。对映选择性铜介导的 4 氧化、azaphilone 2 与含游离胺的环肽 3 的温和偶联以及最终螺胺形成的一锅三步方案均成功高效实现，以产生正确的立体化学产品1a.