picropodophyllic acid | 477-67-8

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基四氢萘木脂素
• 英文名称: picropodophyllic acid
• 英文别名: picropodophyllinic acid；Picropodophyllinsaeure；(5R,6S,7R,8R)-8-hydroxy-7-(hydroxymethyl)-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydrobenzo[f][1,3]benzodioxole-6-carboxylic acid
• CAS: 477-67-8
• 化学式: C₂₂H₂₄O₉
• 分子量: 432.427
• InChiKey: XRBSKUSTLXISAB-HAEOHBJNSA-N

物化性质

• 熔点：
  150-155° and 200-232°
• 比旋光度：
  D21 -100.4° (c = 0.615 in ethanol), -185° (c = 0.746 in pyridine)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  picropodophyllic acid 在 lithium aluminium tetrahydride 、 三甲基氯硅烷 、 草酰氯 、 三氟化硼乙醚 、 二甲基亚砜 、 三乙胺 、 mercury(II) oxide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 27.5h， 生成 (-)-(1R,2S)-1,2-dihydro-1-(3,4,5-trimethoxyphenyl)-2-(hydroxymethyl)-3-formylnaphthalene
  参考文献：
  名称：

  Preparation and cytotoxicity of podophyllotoxin derivatives lacking the lactone ring

  摘要：

  Several cyclolignans lacking of the lactone moiety can easily be prepared from naturally occurring lignans such as podophyllotoxin and deoxypodophyllotoxin by simple chemical transformations. Their cytotoxicity has been studied in four tumoral cell lines. Most of the compounds show similar effects in all the neoplastic systems tested, except the aldehyde 9 (methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate) and the hydrazones 16 and 17 which show a highly selective cytotoxicity towards HT-29 human colon carcinoma. Additionally, several molecular modeling studies have been done with aldehyde 9 and the corresponding saturated aldehyde 13 in comparison with podophyllotoxin. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4020(97)10042-4
• 作为产物：
  描述：

  鬼臼毒素 在 potassium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 生成 picropodophyllic acid
  参考文献：
  名称：

  鬼臼醛和二萜对苯二酚衍生的新杂种对骨肉瘤细胞的选择性

  摘要：

  制备了一个新的分子杂种家族，介于与鬼臼醛有关的环木脂素和几种二萜烯萘氢醌（DNHQ）之间，并在几种人类实体瘤细胞系中评估了其生物学活性，这些细胞系代表了西方世界上最普遍的实体瘤。环木脂体和醌片段都通过脂族或芳族间隔基连接。评价了新的杂种家族的细胞毒性，发现杂种对骨肉瘤细胞MG-63的效力是对MCF-7和HT-29细胞系的几倍。接头中芳环的存在提供了最有效和最有效的试剂，从而改善了母体化合物的细胞毒性。

  DOI：

  10.1021/acsmedchemlett.7b00493

文献信息

• Synthesis and Biological Evaluation of New Podophyllic Aldehyde Derivatives with Cytotoxic and Apoptosis-Inducing Activities
  作者：M Ángeles Castro、José M Miguel del Corral、Pablo A. García、M Victoria Rojo、Janis de la Iglesia-Vicente、Faustino Mollinedo、Carmen Cuevas、Arturo San Feliciano

  DOI：10.1021/jm901373w

  日期：2010.2.11

  Several series of nonlactonic podophyllic aldehyde analogues were prepared and evaluated against several human tumor cell lines. They had different combinations of aldehyde, imine, amine, ester, and amide functions at C-9 and C-9′ of the cyclolignan skeleton. All the compounds synthesized showed cytotoxicity levels in the μM range and below. Within the new series tested, compounds having an aldehyde

  制备了几种非内分泌的鬼臼醛类似物，并针对几种人类肿瘤细胞系进行了评估。他们在cyclolignan骨架的C-9和C-9'处具有醛，亚胺，胺，酯和酰胺官能团的不同组合。合成的所有化合物均显示在μM或以下的细胞毒性水平。在测试的新系列中，在C-9处具有醛或亚胺，在C-9'具有酯的化合物是最有效的，其GI 50值在nM范围内，其中一些对HT-29的效力高出几倍。与A-549癌相比，它可抗MB-231黑色素瘤细胞。细胞周期研究和对微管破坏能力的分析表明，对于结构密切相关的化合物，存在两种不同的细胞死亡诱导机制。
• Über Säurehydrazide aus der Podophyllotoxin-Reihe. 8. Mitteilung über mitosehemmende Naturstoffe
  作者：J. Rutschmann、J. Renz

  DOI：10.1002/hlca.19590420334

  日期：——

  Hydrazide lassen sich entweder direkt oder über die entsprechenden Azide wieder in die ursprünglichen Lactone überführen. So entsteht aus dem neuen Podophyllinsäure-hydrazid das Podophyllotoxin, ein Beweis, dass unter gewissen Bedingungen die Öffnung des trans-Lactonringes bei der Hydrazinspaltung ohne Konfigurationsänderung stattfinden kann. Die sich aus der Existenz dieser erstmals hergestellten

  从鬼臼毒素，脱甲基鬼臼毒素，脱氧鬼臼毒素及其已知的立体异构体以及peltatins开始，可以制备许多具有与起始内酯相同构型的未取代和取代的酰肼。可以将简单的酰肼直接或通过相应的叠氮化物转化回原始的内酯。鬼臼毒素是由新的鬼臼酸酰肼产生的，证明在某些条件下，在肼裂解过程中反式内酯环可以在不改变构型的情况下发生。讨论了由于首次产生的鬼臼苦素的这些衍生物（= 2,3-反酸）的存在而对命名产生的影响。
• Epimerization and hydrolysis of etoposide analogues in aqueous solution.
  作者：Yukio ASO、Yuzuru HAYASHI、Sumie YOSHIOKA、Yasushi TAKEDA、Yasuhiro KITA、Yoshifumi NISHIMURA、Yoji ARATA

  DOI：10.1248/cpb.37.422

  日期：——

  Epimerization and hydrolysis of etoposide and its analogues involving aglycons were examined in alkaline aqueous solution. The trans-lactone compounds such as etoposide were epimerized to the cis-lactone compounds such as picroetoposide, but not hydrolyzed to trans-hydroxy acid derivatives. The cis-lactone compounds were susceptible to the hydrolysis of the lactone ring. The epimerization was accelerated by the presence of the sugar substituent at position 4 and of the methoxy group at position 4'. The epimerization was also affected by the configuration of the hydroxyl group at position 4. The hydrolysis rate of the cis-lactone was decreased by the sugar substituent at position 4, and increased by the methoxy group at position 4'. The configuration of the hydroxyl group at position 4 had no effect. The nuclear magnetic resonance data suggest that the structure of etoposide is more strained and less than that of the aglycon. The acceleration of the epimerization by the sugar substituent may be ascribed to the decrease in the stability of the trans-lactone by glycosidation. The decrease of hydrolysis rate owing to glycosidation may be explained in terms of the steric handrance of the bulky sugar substituent.

  在碱性水溶液中研究了依托泊苷及其类似物涉及炔丙酮的外嵌和水解。依托泊苷等反式内酯化合物被外嵌为吡咯泊苷等顺式内酯化合物，但没有水解为反式羟基酸衍生物。顺式内酯化合物易受内酯环水解的影响。位置 4 上的糖取代基和位置 4'上的甲氧基基团的存在加速了表聚过程。第 4 位羟基的构型也会影响缩合反应。顺式内酯的水解速率因第 4 位的糖取代基而降低，因第 4'位的甲氧基而升高。位于第 4 位的羟基的构型没有影响。核磁共振数据表明，依托泊苷的结构比苷聚体的结构更紧张，更不稳定。糖取代基加速了表聚作用，这可能是由于糖苷化作用降低了反式内酯的稳定性。糖苷化导致水解速率降低的原因可能是笨重的糖取代基的立体牵制作用。
• Immunosuppressive Cyclolignans
  作者：Marina Gordaliza、Glynn T. Faircloth、M Angeles Castro、José M. Miguel del Corral、M Luisa López-Vázquez、Arturo San Feliciano

  DOI：10.1021/jm960023h

  日期：1996.1.1

  The immunosuppressive activity of several lactonic, nonlactonic, and heterocycle-fused cyclolignans has been demonstrated for the first time by use of a T-cell-mediated immune response. Of the compounds tested, 4'-demethyldeoxypodophyllotoxin (8), beta-apopicropodophyllin (6), and the isoxazoline-fused cyclolignan 15 are the most potent with respect to their suppression of activated splenocytes.
• Lignopurines: A new family of hybrids between cyclolignans and purines. Synthesis and biological evaluation
  作者：Ma Ángeles Castro、José Ma. Miguel del Corral、Pablo A. García、Ma Victoria Rojo、Ana C. Bento、Faustino Mollinedo、Andrés M. Francesch、Arturo San Feliciano

  DOI：10.1016/j.ejmech.2012.10.026

  日期：2012.12

  A new family of hybrids between cyclolignans related to podophyllic aldehyde, a non-lactonic cyclolignan, and purines were prepared and evaluated against several human tumour cell lines. Both fragments, cyclolignan and purine, were linked through aliphatic and aromatic chains. The influence on the cytotoxicity of the purine substitution and the nature of the linker is analyzed. The new family was slightly less cytotoxic than the parent podophyllic aldehyde, although the selectivity is maintained or even improved and among the linkers used, the presence of an aromatic ring gave the most potent and selective derivatives within the new series tested. Cell cycle and confocal studies demonstrate that these derivatives interfere with the tubulin polymerization and arrest cells at the G(2)/M phase, in the same way than the parent compounds podophyllotoxin and podophyllic aldehyde do. (C) 2012 Elsevier Masson SAS. All rights reserved.