alpha-盾叶鬼臼素 | 568-53-6

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 中文名称: alpha-盾叶鬼臼素
• 英文名称: (5R,5aR,8aR)-10-Hydroxy-5-(4-hydroxy-3,5-dimethoxy-phenyl)-5,8,8a,9-tetrahydro-5aH-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6-one
• 英文别名: α-peltatin；α-Peltatin-A；alpha-Peltatin；(5aR,8aR,9R)-4-hydroxy-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
• CAS: 568-53-6
• 化学式: C₂₁H₂₀O₈
• 分子量: 400.385
• InChiKey: JGGWNGRBXJWAOC-HKJPBSJPSA-N

物化性质

• 比旋光度：
  D20 -124.8° (c = 0.5 in chloroform)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  8

制备方法与用途

α-pellatin是一种芳基木脂素，具有抗癌症和抗真菌活性，并能抑制DNA拓扑异构酶和微管蛋白聚合。

反应信息

• 作为反应物：
  描述：

  alpha-盾叶鬼臼素 在 palladium on activated charcoal 吡啶 、 4-二甲氨基吡啶 、 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 12.0h， 生成 α-peltatin 5-phenylacetate
  参考文献：
  名称：

  Antitumor agents. 100. Inhibition of human DNA topoisomerase II by cytotoxic ether and ester derivatives of podophyllotoxin and .alpha.-peltatin

  摘要：

  A principal mechanism of action of the clinical antitumor drugs etoposide (1) and teniposide (2) is the inhibition of catalytic activity of type II DNA topoisomerase and concurrent enzyme-mediated production of lethal DNA strand breaks. Substitution of the glycosidic moiety of 1 or 2 by ester and ethers, as well as the esterification and etherification of alpha-peltatin (4) including its glucosidic ethylidene and thenylidene cyclic acetals (25 and 26), has afforded compounds of much less activity than that of 1. The in vitro cytotoxicity (KB) appears to have no correlation with the inhibitory activity of the human DNA topoisomerase II.

  DOI：

  10.1021/jm00123a016
• 作为产物：
  描述：

  (3R,4R)-3,4-bis[(4-hydroxy-3-methoxyphenyl)methyl](514C)oxolan-2-one 生成 alpha-盾叶鬼臼素
  参考文献：
  名称：

  BROOMHEAD, A. JANE;RAHMAN, MAIADA M. A.;DEWICK, PAUL M.;JACKSON, DAVID E.+, PHYTOCHEMISTRY, 30,(1991) N, C. 1489-1492

  摘要：

  DOI：

文献信息

• Studies in Sugar Chemistry VII1). Glucuronides of Podophyllum Derivatives
  作者：Abraham Nudelman、Margaretta Ruse、Hugo E. Gottlieb、Craig Fairchild

  DOI：10.1002/ardp.19973300904

  日期：——

  The antitumor activities of several glucuronide methyl esters of podophyllum derivatives were tested in vitro against two human tumor cell lines and their drug resistant sublines. The most active compound studied was methyl (4′‐carbobenzoxy‐4′‐demethylepipodophyllotoxin‐D‐glucopyranoside)uronate 19. Compound 19 was as potent in a colon carcinoma model and was twice as potent in a lung carcinoma model

  在体外测试了几种鬼臼衍生物的葡萄糖醛酸甲酯对两种人类肿瘤细胞系及其耐药亚系的抗肿瘤活性。研究的最活跃的化合物是甲基（4'-羧基苯甲氧基-4'-去甲基表鬼臼毒素-D-吡喃葡萄糖苷）糖醛酸 19。化合物 19 在结肠癌模型中的效力与依托泊苷 6 在肺癌模型中的效力相同。然而，在 vivo 小鼠白血病 P388 模型中，它仅具有边缘活性，在 37 mg/kg (iv) 时最大 T/C% 值为 125。
• (−)-Arctigenin as a Lead Structure for Inhibitors of Human Immunodeficiency Virus Type-1 Integrase
  作者：Eckart Eich、Heinz Pertz、Macki Kaloga、Jutta Schulz、Mark R. Fesen、Abhijit Mazumder、Yves Pommier

  DOI：10.1021/jm950387u

  日期：1996.1.1

  congener with two catechol substructures (7) was found to be the most active compound in this study. 7 was also a potent inhibitor of the "disintegration" reaction which models the reversal of the strand transfer reaction. The inhibitory activity of 7 with the core enzyme fragment consisting of amino acids 50-212 suggests that the binding site of 7 resides in the catalytic domain.

  发现天然二苄基丁内酯型木质素（-）-arctigenin（2）是一种人类免疫缺陷病毒1型（HIV-1）在感染的人类细胞系统中复制的抑制剂，可抑制前病毒DNA整合到细胞DNA基因组中。在本研究中，2用纯化的HIV-1整合酶进行了测试，发现在裂解（3'-加工）和整合（链转移）测定中无活性。然而，以儿茶酚亚结构为特征的半合成3-O-去甲基化同源物9在两种测定中均表现出显着的活性。用30种天然（1-6），半合成（7-21）和合成（37-43、45、46）的木脂素进行结构-活性关系研究表明，（1）内酯部分至关重要，因为带有丁烷-1的化合物，4-二醇或四氢呋喃的亚结构以及木脂酰胺类似物缺乏活性，（2）酚羟基的数量和排列对于木质素的活性很重要。在本研究中，发现具有两个邻苯二酚亚结构的同类物（7）是活性最高的化合物。7也是“崩解”反应的有效抑制剂，其模拟了链转移反应的逆转。7对由氨基酸50-212组成的核
• Lignans and related phenols. Part 18. The synthesis of quinones from podophyllotoxin and its analogues
  作者：David C. Ayres、Timothy J. Ritchie

  DOI：10.1039/p19880002573

  日期：——

  The preparation of quinones from podophyllotoxin and peltatins of the aryltetrahydronaphthalene class by oxidative demethylation is described. The derivation of 2′-substituted ortho-quinones from these products by the reductive addition of azide, bromide, and chloride and subsequent oxidation by periodate is reported. Acid-catalysed reactions of ortho-quinones with alcohols are described including

  描述了通过鬼臼四氢萘类的鬼臼毒素和peltatins通过氧化脱甲基制备醌的方法。据报道，通过叠氮化物，溴化物和氯化物的还原性加成以及随后的高碘酸盐的氧化，从这些产物中衍生出2'-取代的邻醌。描述了邻醌与醇的酸催化反应，包括还原性甲基化的不寻常实例。
• Lignanglucoside aus<i>Podophyllum peltatum L</i>. 7. Mitteilung über mitosehemmende Naturstoffe
  作者：A. von Wartburg、E. Angliker、J. Renz

  DOI：10.1002/hlca.19570400525

  日期：——

  From the rhizomes of american Podophyllum peltatum L. it was possible to isolate and characterize four lignan glucosides with anti-mitotic activity: podophyllotoxin-β-D-glucoside (IX), β-peltatin-β-D-glucoside (XI), 4′-demethylpodophyllotoxin-β-D-glucoside (X) and α-peltatin-β-u-glucoside (XII). The constitution of β-peltatin-β-D- glucoside was deduced from the fact that enzymatic cleavage with emulsin

  从美洲鬼臼的根茎。可以分离并鉴定具有抗有丝分裂活性的四种木脂素葡糖苷：鬼臼毒素-β-D-葡糖苷（IX），β-类维生素A-β-D-葡糖苷（XI），4'-去甲基鬼臼毒素-β-D-葡糖苷（X）和α-peltatin-β-u-葡萄糖苷（XII）。根据以下事实推论β-类维生素A-β-D-葡萄糖苷的组成：用乳胶酶解产生D-葡萄糖和已知的β-类胡萝卜素。α-Peltatin-β-D-葡萄糖苷是鬼臼类中第一个以结晶形式分离的天然葡萄糖苷，经乳化酶水解后分解为D-葡萄糖和α-peltatin。可以通过甲基化为鬼臼毒素-β-D-葡萄糖苷和β-peltatin-β-D-的甲基化来确定4'-去甲基鬼臼毒素-β-D-葡萄糖苷和α-peletatin-β-D-葡萄糖苷中糖成分的位置。糖苷。
• Compositions and methods for producing podophyllotoxin derivatives
  申请人：The Board of Trustees of the Leland Stanford Junior University

  公开号：US10472688B2

  公开（公告）日：2019-11-12

  The present invention provides compositions and methods for biosynthetically producing podophyllotoxin intermediates and derivatives including enzymes and their equivalents involved in the biosynthetic production of podophyllotoxin intermediates and derivatives.

  本发明提供了生物合成生产荚膜毒素中间体和衍生物的组合物和方法，包括参与生物合成生产荚膜毒素中间体和衍生物的酶及其等效物。