2,3-(methylenedioxy)-5-methyl-6-ethoxy-7-benzyloxy-8-methoxy-5,6-dihydrobenzo[c]phenanthridine | 209157-82-4

• 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: 2,3-(methylenedioxy)-5-methyl-6-ethoxy-7-benzyloxy-8-methoxy-5,6-dihydrobenzo[c]phenanthridine
• 英文别名: 13-ethoxy-2-methoxy-12-methyl-1-phenylmethoxy-13H-[1,3]benzodioxolo[5,6-c]phenanthridine
• CAS: 209157-82-4
• 化学式: C₂₉H₂₇NO₅
• 分子量: 469.537
• InChiKey: FYMDUFRJDZQQOV-UHFFFAOYSA-N

物化性质

• 熔点：
  141-149 °C
• 沸点：
  643.641±55.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.328±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,3-(methylenedioxy)-5-methyl-6-ethoxy-7-benzyloxy-8-methoxy-5,6-dihydrobenzo[c]phenanthridine 在 manganese(IV) oxide 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 生成 2-Methoxy-13-methyl-1-phenylmethoxy-[1,3]benzodioxolo[5,6-c]phenanthridine
  参考文献：
  名称：

  Synthesis of derivatives of NK109, 7-OH Benzo[c]phenanthridine alkaloid, and evaluation of their cytotoxicities and reduction-resistant properties

  摘要：

  The N-5-C-6 double bond of NK109 (an antitumor benzo[c]phenanthridine alkaloid) is easily reduced under biological environment. To suppress the inactivation caused by reduction, we synthesized 5-, 6-, and 8-substituted NK109. 5-Substituted derivatives (4a-c) were reduced more easily than NK109. 6-Substituted ones (10a-f) inhibited biological reduction, but showed weak cytotoxic activity. 8-O-Substituted ones (13a-h), especially 8-O-hydroxyethyl NK109 (13d), suppressed biological reduction and exhibited strong cytotoxic activity. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(00)00467-4
• 作为产物：
  描述：

  2,3-(methylenedioxy)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine 在 sodium hydroxide 作用下， 以 甲苯 为溶剂， 反应 37.0h， 生成 2,3-(methylenedioxy)-5-methyl-6-ethoxy-7-benzyloxy-8-methoxy-5,6-dihydrobenzo[c]phenanthridine
  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

• Design and synthesis of a novel water soluble benzotetrazepinone
  作者：Beatrice Dumont-Hornebeck、Yi Ning Strube、Daniela Vasilescu、Bertrand Jacques Jean-Claude

  DOI：10.1016/s0960-894x(00)00461-3

  日期：2000.10

  In order to confer water solubility to the benzotetrazepinone ring system, the synthesis of 12 was undertaken. The design and synthesis of 12 were based upon previously established structural requirements for the stability of the 1,2,3,5-tetrazepin-4-one ring system. Tetrazepinone 12 was extremely water soluble and was 10-fold more potent than its imidazo-1,2,3,5-tetrazin-4-one counterpart 1a, against

  为了赋予苯并四氮杂酮环系统水溶性，进行了12的合成。12的设计和合成是基于先前确定的1,2,3,5-tetrazepin-4-one环系统稳定性的结构要求。对人MCF-7乳腺癌细胞而言，四嗪酮12极易溶于水，并且其效价比其咪唑-1,2,3,5-四嗪-4-酮1a的效价高10倍。
• Phenanthridinium derivatives
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：US06187783B1

  公开（公告）日：2001-02-13

  A novel phenanthridinium derivative represented by general formula (A): wherein R1 is a substituted or unsubstituted lower aliphatic hydrocarbon group; R is an aliphatic hydrocarbon chain having 2 to 6 carbon atoms which may optionally be substituted with a substituent selected from the group consisting of a lower alkyl group, a halogen and a hydroxy group; each of Y and Z independently represents a hydrogen, a hydroxy or a lower alkoxy group; or Y and Z are combined together to form methylenedioxy or a phenyl ring; and, X− is an acid residue or a hydrogen acid residue, exhibits an antitumor activity and has resistance to chemical reduction as well as biological metabolic reactions and is thus advantageous for use as a medicine.

  一种新的苯并三氮杂环衍生物，其通式表示为（A）：其中R1是取代或未取代的低级脂肪烃基；R是具有2至6个碳原子的脂肪烃链，可以选择性地被取代为来自以下组的取代基：低级烷基，卤素和羟基；每个Y和Z独立地表示氢，羟基或低级烷氧基；或Y和Z组合成亚甲二氧基或苯环；而X-是酸残基或氢酸残基。该化合物具有抗肿瘤活性，具有抗化学还原和生物代谢反应的抵抗力，因此适用于作为药物。
• NOVEL PHENANETHRIDINIUM DERIVATIVES
  申请人：NIPPON KAYAKU KABUSHIKI KAISHA

  公开号：EP0947514A1

  公开（公告）日：1999-10-06

  A novel phenanthridinium derivative represented by general formula (A): wherein R1 is a substituted or unsubstituted lower aliphatic hydrocarbon group; R is an aliphatic hydrocarbon chain having 2 to 6 carbon atoms which may optionally be substituted with a substituent selected from the group consisting of a lower alkyl group, a halogen and a hydroxy group; each of Y and Z independently represents a hydrogen, a hydroxy or a lower alkoxy group; or Y and Z are combined together to form methylenedioxy or a phenyl ring; and, X- is an acid residue or a hydrogen acid residue, exhibits an antitumor activity and has resistance to chemical reduction as well as biological metabolic reactions and is thus advantageous for use as a medicine.

  通式(A)代表的新型菲啶衍生物： 其中 R1 是取代或未取代的低级脂肪族烃基；R 是具有 2 至 6 个碳原子的脂肪族烃链，可任选被选自低级烷基、卤素和羟基的取代基取代；Y 和 Z 各自独立地代表氢、羟基或低级烷氧基；或 Y 和 Z 结合在一起形成亚甲基二氧基或苯基环； X-是酸残基或氢酸残基，具有抗肿瘤活性，耐化学还原和生物代谢反应，因此有利于用作药物。
• JPH10152474A
  申请人：——

  公开号：JPH10152474A

  公开（公告）日：1998-06-09
• US6187783B1
  申请人：——

  公开号：US6187783B1

  公开（公告）日：2001-02-13