2,3-(methylenedioxy)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine | 142886-80-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2,3-(methylenedioxy)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine
• 英文别名: 7-benzyloxy-8-methoxy-2,3-(methylenedioxy)-benzo[c]phenanthridine；2-methoxy-1-phenylmethoxy-[1,3]benzodioxolo[5,6-c]phenanthridine
• CAS: 142886-80-4
• 化学式: C₂₆H₁₉NO₄
• 分子量: 409.441
• InChiKey: JSGMFWXYGVRZPN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  31
• 可旋转键数：
  4
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-(methylenedioxy)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine 在 palladium 10% on activated carbon 、 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以72%的产率得到isodecarine
  参考文献：
  名称：

  Synthesis of Isodecarine

  摘要：

  DOI：

  10.3987/com-07-s(u)57
• 作为产物：
  描述：

  6-溴-2-羟基于-甲氧基苯甲醛 在 manganese(IV) oxide 、 偶氮二异戊腈 、 三正辛基氢化锡 、 dimethylamine borane 、 potassium carbonate 、 溶剂黄146 、 potassium iodide 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 13.67h， 生成 2,3-(methylenedioxy)-7-benzyloxy-8-methoxy-benzo[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
• 作为试剂：
  描述：

  2,3-(methylenedioxy)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine 、 三氟乙酸 、 3-溴-1-丙醇 、 三(三甲基硅基)硅烷 、 偶氮二异丁腈 在 2,3-(methylenedioxy)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine 、 2,2,2-三氟乙酸盐 、 碳酸氢钠 、 二氯甲烷 、 水 、 Sodium sulfate-III 、 silica gel 、 toluene-ethyl acetate 作用下， 以 乙腈 为溶剂， 反应 1.5h， 以to give 2,3-(methylenedioxy)-6-(3-hydroxypropyl)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine (0.210 g, yield 15%) as light brown powders的产率得到2,3-(methylenedioxy)-6-(3-hydroxypropyl)-7-benzyloxy-8-methoxy-benzo[c]phenanthridine
  参考文献：
  名称：

  Phenanthridinium derivatives

  摘要：

  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到6个碳原子的脂肪烃链，可以选择性地被取代，所选取代基来自于由低级烷基、卤素和羟基组成的取代基；Y和Z各自独立地表示氢、羟基或低级烷氧基；或者Y和Z结合在一起形成亚甲二氧基或苯环；X-是酸残基或氢酸残基。该化合物具有抗肿瘤活性，并具有抗化学还原和生物代谢反应的特性，因此非常适用于药物。

  公开号：

  US06187783B1

文献信息

• PROCESS FOR PRODUCING BENZOÝc¨PHENANTHRIDINE DERIVATIVE
  申请人：NIPPON KAYAKU KABUSHIKI KAISHA

  公开号：EP1813617A1

  公开（公告）日：2007-08-01

  A compound represented by the following formula (1): [wherein R1 and R2 each independently represents hydroxy, provided that R1 and R2 may be bonded to each other to form methylenedioxy, etc.; X represents halogeno; and R3 represents a protective group] is subjected to a cyclization reaction with the aid of an organic silyl hydride and then aromatized with an oxidizing agent to produce a benzo[c]phenanthridine derivative represented by the following formula (2): [wherein R1, R2, and R3 have the same meanings as defined above].

  通过有机硅基氢化物辅助下，将以下化合物（1）所代表的化合物经过环化反应，然后用氧化剂芳构化，产生以下化合物（2）所代表的苯并[c]苯并喹啉衍生物：【其中R1和R2各自独立代表羟基，但R1和R2可以结合形成亚甲二氧基等；X代表卤素；R3代表保护基】。
• Formal Synthesis of Nitidine and NK109 via Palladium-Catalyzed Domino Direct Arylation/<i>N</i>-Arylation of Aryl Triflates
  作者：Mathieu Blanchot、David A. Candito、Florent Larnaud、Mark Lautens

  DOI：10.1021/ol200174g

  日期：2011.3.18

  The use of aryl triflates as reaction partners in a palladium-catalyzed domino direct arylation/N-arylation provides a great advantage due to the availability of starting materials. Furthermore, it allows expedient access to biologically interesting benzo[c]phenanthridine alkaloids.

  由于起始原料的可获得性，在钯催化的多米诺骨牌直接芳基化/ N-芳基化中使用芳基三氟甲磺酸酯作为反应伙伴具有很大的优势。此外，它允许方便地获得生物学上令人感兴趣的苯并[ c ]菲啶生物碱。
• 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。
• 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。