7-hydroxy-8-methoxy-5-methyl-2,3-methylenedioxybenzo[c]phenanthridium sulfate

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 苯并菲啶生物碱
• 英文名称: 7-hydroxy-8-methoxy-5-methyl-2,3-methylenedioxybenzo[c]phenanthridium sulfate
• 英文别名: 7-hydroxy-8-methoxy-5-methyl-2,3-methylenedioxybenzo[c]phenanthridin-5-iumhydrogensulfate dihydrate；NK109；2,3-(methylenedioxy)-5-methyl-7-hydroxy-8-methoxy-benzo[c]phenanthridinium hydrogen sulfate salt；Hydron;2-methoxy-12-methyl-[1,3]benzodioxolo[5,6-c]phenanthridin-12-ium-1-ol;sulfate
• 化学式: C₂₀H₁₆NO₄*HO₄S
• 分子量: 431.423
• InChiKey: CSHFAEFWVIKQGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.42
• 重原子数：
  30
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  138
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-hydroxy-8-methoxy-5-methyl-2,3-methylenedioxybenzo[c]phenanthridium sulfate 在 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 反应 2.0h， 生成 7-O-demethyldihydrochelerythrine
  参考文献：
  名称：

  NK109，一种抗肿瘤的苯并[c]菲啶生物碱的结构考虑。

  摘要：

  合成的苯并[c]菲啶，NK109（7-羟基-2、3-亚甲基二氧基-5-甲基-8-甲氧基苯并[c]菲啶鎓硫酸氢二水合物）和天然苯并[c]菲啶的抗肿瘤活性在25℃下进行了测试。体外和体内。NK109（3）具有最高的活性。NK109的结构类似于法加宁和法加替丁。但是，它在C-7处有酚羟基。NK109作为共振杂合体存在，酮胺和两性离子形式存在于中性介质中。共振杂化体是阳离子的，并具有分子平面性。这些被认为对于苯并[c]菲啶鎓盐的抗肿瘤活性是必不可少的。另一方面，在相同条件下，结构相似的苯并[c]苯乙啶生物碱，白屈菜红碱和血红素碱作为假碱基存在。后者在体内不显示抗肿瘤活性，可能是因为它们同时失去了铵区域和分子平面性。因此，从生物学条件下的结构来看，3可以认为是苯并[c]菲啶鎓盐的新类别。

  DOI：

  10.1021/np990005d
• 作为产物：
  描述：

  2,3-(methylenedioxy)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine 在 sodium hydroxide 、 硫酸 作用下， 以 甲苯 为溶剂， 反应 38.0h， 生成 7-hydroxy-8-methoxy-5-methyl-2,3-methylenedioxybenzo[c]phenanthridium sulfate
  参考文献：
  名称：

  Synthesis of NK109, an Anticancer Benzo[c]phenanthridine Alkaloid

  摘要：

  A total synthesis of NK109 (7-hydroxy-8-methoxy-5-methyl-2,3-methylenedioxybenzo[c]phenanthridinium hydrogensulfate dihydrate), an anticancer benzo[c]phenanthridine alkaloid, is reported. The primary structure of this compound was erroneously communicated in 1973 as fagaridine (from Fagara xanthoxyloides) which is the 8-hydroxy regioisomer. NK109 has not yet been isolated from a natural source and therefore can only be obtained by synthesis. To study a wide variety of analogues, we decided to use a synthetic route via substituted benzylamine 5, which was obtained from the appropriate benzaldehyde and naphthylamine units. The benzo[c]phenanthridine ring was constructed by radical cyclization with tri-n-octyltin hydride and 2,2'-azobis(2-methylbutyronitrile), followed by oxidative aromatization with MnO2. The resulting benzo[c]phenanthridine 6 was successfully methylated with methyl 2-nitrobenzenesulfonate. After deprotection of the benzyl group and subsequent hydration, NK109 was obtained. All reactions were performed under normal conditions. Purification was achieved only by recrystallization to;give an overall yield of 40%.

  DOI：

  10.1021/jo9718758

文献信息

• Process for preparing benzo\x9bc!phenanthridinium derivatives, novel
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：US05747502A1

  公开（公告）日：1998-05-05

  The present invention relates to benzo\x9bc!phenanthridinium derivative of the general formula A: ##STR1## wherein M and N individually represent a hydroxyl or lower alkoxy group, or M and N simultaneously represent a hydrogen atom or together form a methylenedioxy group, X.sup.- represents an acid residue or a hydrogen acid residue, and R represents a lower alkyl group, and a process for preparing such derivatives. The compounds exhibit both potent antitumor activity and platelet aggregation inhibition activity, and are expected to be useful for the treatment of tumors. The process has good reproducibility and may be effected under moderate conditions, and therefore the process is practically useful. In addition, hydrogen salts of the present compounds have an enhanced stability, which is an advantage in formulating the same into pharmaceutical preparations.

  本发明涉及一般式A的苯并[中文字符]菲啉衍生物：其中M和N分别代表一个羟基或较低的烷氧基团，或者M和N同时代表一个氢原子或一起形成一个亚甲二氧基基团，X.sup.-代表一个酸残基或一个氢酸残基，R代表一个较低的烷基团，以及制备这种衍生物的方法。这些化合物表现出强大的抗肿瘤活性和抑制血小板聚集活性，预计对肿瘤治疗有用。该方法具有良好的可重复性，可以在适中条件下实施，因此该方法在实际中是有用的。此外，本化合物的氢盐具有增强的稳定性，这是将其配制成药物制剂的优势。
• Process for preparing benzo[C]phenanthridinium derivatives, and novel compounds prepared by said process
  申请人：NIPPON KAYAKU KABUSHIKI KAISHA

  公开号：EP0487930A1

  公开（公告）日：1992-06-03

  The present invention relates to a process for preparing benzo[c]phenanthridinium derivatives of the general formula A: wherein M and N individually represent a hydroxyl or lower alkoxy group, or M and N simultaneously represent a hydrogen atom or together form a methylenedioxy group, X⁻ represents an acid residue or a hydrogen acid residue, and R represents a lower alkyl group. This process has good reproducibility and may be effected under moderate conditions, and therefore the process is practically useful. Also, it has been found that certain novel benzo[c]phenanthridinium derivatives, prepared by the present process, have not only an antitumor activity but also an inhibition activity on blood platelet aggregation. In addition, hydrogen salts of the present compounds have an enhanced stability, which is an advantage in formulating into phamaceutical preparations.

  本发明涉及一种制备通式 A 的苯并[c]菲啶鎓衍生物的工艺： 其中 M 和 N 分别代表羟基或低级烷氧基，或 M 和 N 同时代表氢原子或共同形成亚甲基二氧基，X- 代表酸残基或氢酸残基，R 代表低级烷基。该工艺具有良好的重现性，可在中等条件下进行，因此该工艺非常实用。此外，还发现通过本工艺制备的某些新型苯并[c]菲啶衍生物不仅具有抗肿瘤活性，还具有抑制血小板聚集的活性。此外，本发明化合物的氢盐具有更高的稳定性，这在配制成医药制剂方面具有优势。
• Benzo[C]phenanthridinium derivatives
  申请人：NIPPON KAYAKU KABUSHIKI KAISHA

  公开号：EP0487930B1

  公开（公告）日：1999-03-24
• Revision of the Structure of Fagaridine Based on the Comparison of UV and NMR Data of Synthetic Compounds
  作者：Takeshi Nakanishi、Masanobu Suzuki

  DOI：10.1021/np980193s

  日期：1998.10.1

  Fagaridine is a quaternary benzo[c]phenanthridine alkaloid, originally isolated from Fagara xanthoxyloides in 1973. The assigned structure of this alkaloid was 7-hydroxy-8-methoxy-5-methyl-2,3-(methylenedioxy)-benzo[c]phenanthridinium (1). We have synthesized this compound, coded NK109, aiming at a practical antitumor drug, and during synthetic studies we questioned the original assigned structure. Thus, we synthesized 8-hydroxy-7-methoxy-5-methyl-2,3-(methylenedioxy)benzo[c]phenanthridinium (2), isomer of the assigned structure, and compared the spectroscopic data of both 1 and 2. The NMR data of 1 and 2 were very similar, but the UV spectra were completely different. The UV data for fagaridine agreed with these for 2; consequently, the true structure of fagaridine is 2, not 1.
• US5747502A
  申请人：——

  公开号：US5747502A

  公开（公告）日：1998-05-05