(9S,12S)-12-(tert-Butoxycarbonyl-methyl-amino)-4-methoxy-10-methyl-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3(19),4,6,14(18),15-hexaene-9-carboxylic acid benzyl ester | 304466-90-8

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物
• 英文名称: (9S,12S)-12-(tert-Butoxycarbonyl-methyl-amino)-4-methoxy-10-methyl-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3(19),4,6,14(18),15-hexaene-9-carboxylic acid benzyl ester
• 英文别名: benzyl (9S,12S)-4-methoxy-10-methyl-12-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]-11-oxo-2-oxa-10-azatricyclo[12.2.2.13,7]nonadeca-1(16),3,5,7(19),14,17-hexaene-9-carboxylate
• CAS: 304466-90-8
• 化学式: C₃₃H₃₈N₂O₇
• 分子量: 574.674
• InChiKey: JBOMHBUQEZXSHU-SVBPBHIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  42
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  94.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (9S,12S)-12-(tert-Butoxycarbonyl-methyl-amino)-4-methoxy-10-methyl-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3(19),4,6,14(18),15-hexaene-9-carboxylic acid benzyl ester 在 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 、 三氟乙酸 作用下， 以 四氢呋喃 为溶剂， 反应 51.0h， 生成 benzyl (5S,8S)-36-methoxy-8-((6R,9S,12S)-12-(4-methoxybenzyl)-N,2,2,6,9,11-hexamethyl-4,7,10,13-tetraoxo-3-oxa-5,8,11,14-tetraazahexadecan-16-amido)-6-methyl-7-oxo-2-oxa-6-aza-1(1,4),3(1,3)-dibenzenacyclononaphane-5-carboxylate
  参考文献：
  名称：

  [Gly-1] RA-VII，[Gly-2] RA-VII和[Gly-4] RA-VII的合成。RA-VII的甘氨酸类似物，一种来自Rubia植物的抗肿瘤双环六肽

  摘要：

  合成了RA-VII（1）的三种类似物，这是一种来自Rubia植物的抗肿瘤双环六肽。三个类似物，[甘氨酸- 1] RA-VII（4），[甘氨酸- 2] RA-VII（5），和[甘氨酸- 4] RA-VII（6），其中在这三个丙氨酸残基之一1通过将甘氨酸残基代替，通过将由1的降解获得的环异酪氨酸单元与三种不同的含甘氨酸的四肽连接，然后进行大环化，来制备α-氨基乙酸。在这三个类似物中，类似物4表现出最高的细胞毒性活性。NMR研究表明，溶液中类似物4的构象结构及其比率与天然肽1非常相似，表明Ala-2和Ala-4处的甲基对于产生生物活性构象应是必不可少的，而d -Ala-1处的甲基则不是必需的。

  DOI：

  10.1021/jo030293p
• 作为产物：
  描述：

  (9S,12S)-12-(tert-Butoxycarbonyl-methyl-amino)-4-methoxy-10-methyl-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3(19),4,6,14(18),15-hexaene-9-carbothioic acid S-methyl ester 在 lithium hydroxide 、 双氧水 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 2.33h， 生成 (9S,12S)-12-(tert-Butoxycarbonyl-methyl-amino)-4-methoxy-10-methyl-11-oxo-2-oxa-10-aza-tricyclo[12.2.2.1^3,7]nonadeca-1(17),3(19),4,6,14(18),15-hexaene-9-carboxylic acid benzyl ester
  参考文献：
  名称：

  Degradation of an antitumour bicyclic hexapeptide RA-VII into cycloisodityrosines

  摘要：

  抗肿瘤双环六肽 RA-VII 1 通过双（硫酰胺）中间体 6 以高效的方式降解产生了受保护的环异酪氨酸。

  DOI：

  10.1039/b004459h

文献信息

• Isolation, structural elucidation, and synthesis of RA-XVII, a novel bicyclic hexapeptide from Rubia cordifolia, and the effect of side chain at residue 1 upon the conformation and cytotoxic activity
  作者：Yukio Hitotsuyanagi、Hiroshi Ishikawa、Tomoyo Hasuda、Koichi Takeya

  DOI：10.1016/j.tetlet.2003.11.112

  日期：2004.1

  A novel antitumor bicyclic hexapeptide RA-XVII was isolated from the roots of Rubia cordifolia. By spectral studies and synthetic approach, its structure was determined to be [D-2-aminobutyric acid-1]deoxybouvardin. Studies on the effect of side chain at residue 1 on cytotoxic activity and conformation showed that although it had little effect on the conformation of the molecule, it decreased the activity

  从茜草的根中分离到一种新的抗肿瘤双环六肽RA-XVII 。通过光谱研究和合成方法，确定其结构为[D-2-氨基丁酸-1]脱氧布瓦丁。关于残基1的侧链对细胞毒性活性和构象影响的研究表明，尽管它对分子构象影响很小，但随着其增长，其活性降低。
• CHEMICAL ENTITIES AND THERAPEUTIC USES THEREOF
  申请人：The Regents of the University of Colorado, a body corporate

  公开号：US20150343016A1

  公开（公告）日：2015-12-03

  The present invention describes the use of translation inhibitors for the treatment of cancer and other disorders. Described herein are translation-inhibiting compounds, and methods of using those compounds for the treatment of cancer and other disorders. In some aspects the compounds inhibit translation elongation at the ribosome. In some aspects the compounds are used alone or in combination with known therapies.

  本发明描述了使用翻译抑制剂治疗癌症和其他疾病的方法。在此所描述的是翻译抑制化合物，以及使用这些化合物治疗癌症和其他疾病的方法。在某些方面，这些化合物抑制核糖体上的翻译延伸。在某些方面，这些化合物单独或与已知的治疗方法联合使用。
• Structures of cytotoxic bicyclic hexapeptides, RA-XIX, -XX, -XXI, and -XXII, from Rubia cordifolia L.
  作者：Ji-Ean Lee、Yukio Hitotsuyanagi、Koichi Takeya

  DOI：10.1016/j.tet.2008.01.094

  日期：2008.4

  Novel bicyclic hexapeptides, RA-XIX, -XX, -XXI, and -XXII, were isolated from the roots of Rubia cordifolia L. The structures of RA-XIX and RA-XX were established by semisynthesis from a cycloisodityrosine, derived from previously reported RA-VII, and those of RA-XXI and RA-XXII by chemical correlation with RA-XX and previously reported RA-VIII, respectively. The IC50 values of these new peptides against

  从茜草的根中分离出新颖的双环六肽RA-XIX，-XX，-XXI和-XXII。RA -XIX和RA-XX的结构是通过半合成从环异二酪氨酸衍生而来的，该化合物来自先前的报道RA-VII，RA-XXI和RA-XXII分别通过与RA-XX和先前报道的RA-VIII的化学相关性分析。这些新肽对P-388白血病细胞的IC 50值为0.013-0.63μg/ mL。
• Design and synthesis of a bis(cycloisodityrosine) analogue of RA-VII, an antitumor bicyclic hexapeptide
  作者：Ji-Ean Lee、Yukio Hitotsuyanagi、Yoshie Nakagawa、Saori Kato、Haruhiko Fukaya、Koichi Takeya

  DOI：10.1016/j.bmcl.2008.10.064

  日期：2008.12

  An analogue of an antitumor bicyclic hexapeptide RA-VII was prepared, in which the Ala-2 and Tyr-3 residues of RA-VII were replaced by a cycloisodityrosine unit. In the crystalline state, the peptide backbone structures and the side-chain conformations at Tyr-3, Tyr-5, and Tyr-6 of this analogue and of RA-II were very similar. This analogue, however, showed much weaker cytotoxicity against P-388 leukemia cells than parent RA-VII. (C) 2008 Elsevier Ltd. All rights reserved.
• Semisynthesis of an Analogue of Antitumor Bicyclic Hexapeptide RA-VII by Fixing the Ala-2/Tyr-3 Bond to <i>Cis</i> by Incorporating a Triazole <i>cis</i>-Amide Bond Surrogate
  作者：Yukio Hitotsuyanagi、Shuichi Motegi、Tomoyo Hasuda、Koichi Takeya

  DOI：10.1021/ol040005r

  日期：2004.4.1

  We prepared an analogue of an antitumor bicyclic hexapeptide RA-VII whose amide configuration between residues 2 and 3 was fixed to cis by incorporating a triazole cis-amide bond surrogate. This analogue was shown, by NMR studies, to take almost the same conformation as that of the minor conformer of RA-VII. It showed no cytotoxic activity.