[1,4'] Bipiperidinyl-1'-carboxylic acid 4-nitrophenylester | 202745-10-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: [1,4'] Bipiperidinyl-1'-carboxylic acid 4-nitrophenylester
• 英文别名: (4-nitrophenyl) 4-piperidin-1-ylpiperidine-1-carboxylate
• CAS: 202745-10-6
• 化学式: C₁₇H₂₃N₃O₄
• 分子量: 333.387
• InChiKey: MYRYEHQHXYLMED-UHFFFAOYSA-N

物化性质

• 沸点：
  478.1±45.0 °C(Predicted)
• 密度：
  1.264±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  78.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [1,4'] Bipiperidinyl-1'-carboxylic acid 4-nitrophenylester 在 palladium on activated charcoal 吡啶 、 三光气 、 氢气 、 六甲基二锡 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 乙酸乙酯 、 苯 为溶剂， 反应 26.0h， 生成 伊立替康
  参考文献：
  名称：

  A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles

  摘要：

  A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with propargyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta- and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.

  DOI：

  10.1002/(sici)1521-3765(199801)4:1<67::aid-chem67>3.0.co;2-f
• 作为产物：
  描述：

  4-哌啶基哌啶 、 对硝基苯基氯甲酸酯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以79%的产率得到[1,4'] Bipiperidinyl-1'-carboxylic acid 4-nitrophenylester
  参考文献：
  名称：

  A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles

  摘要：

  A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with propargyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta- and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.

  DOI：

  10.1002/(sici)1521-3765(199801)4:1<67::aid-chem67>3.0.co;2-f

文献信息

• Camptothecin analogs and methods of preparation thereof
  申请人：——

  公开号：US20020193598A1

  公开（公告）日：2002-12-19

  A compound and a method of synthesizing a compound having the following general formula (1): 1 wherein R 1 and R 2 are independently the same or different and are hydrogen, an alkyl group, an alkenyl group, a benzyl group, an alkynyl group, an alkoxy group, an aryloxy group, an acyloxy group, —OC(O)OR d , wherein R d is an alkyl group, a carbamoyloxy group, a halogen, a hydroxy group, a nitro group, a cyano group, an azido group, a formyl group, a hydrazino group, an acyl group, an amino group, —SR c , wherein, R c is hydrogen, an acyl group, an alkyl group, or an aryl group, or R 1 and R 2 together form a group of the formula —O(CH 2 ) n O— wherein n represents the integer 1 or 2; R 3 is H, F, a halogen atom, a nitro group, an amino group, a hydroxy group, or a cyano group; or R 2 and R 3 together form a group of the formula —O(CH 2 ) n O— wherein n represents the integer 1 or 2; R 8 is H, a trialkylsilyl group, F, a C 1-3 alkyl group, a C 2-3 alkenyl group, a C 2-3 alkynyl group, or a C 1-3 alkoxy group; R 5 is a C 1-10 alkyl group, an allyl group, a benzyl group or a propargyl group; and R 6 , R 7 and R 8 are independently a C 1-10 alkyl group, a C 2-10 alkenyl group, a C 2-10 alkynyl group, an aryl group or a —(CH 2 ) N R 9 group, wherein N is an integer within the range of 1 through 10 and R 9 is a hydroxy group, alkoxy group, an amino group, an alkylamino group, a dialkylamino group, a halogen atom, a cyano group or a nitro group; and R 11 is an alkylene group or an alkenylene group, and pharmaceutically acceptable salts thereof.

  一种具有以下通式（1）的化合物及其合成方法：其中R1和R2独立地相同或不同，可以是氢、烷基、烯基、苯基、炔基、烷氧基、芳基氧基、酰氧基、—OC（O）ORd，其中Rd是烷基、氨基甲酰氧基、卤素、羟基、硝基、氰基、偶氮基、甲酰基、肼基、酰基、氨基、—SRc，其中，Rc是氢、酰基、烷基或芳基，或R1和R2共同形成式为—O（CH2）nO—的基团，其中n表示整数1或2；R3是H、F、卤素原子、硝基、氨基、羟基或氰基；或R2和R3共同形成式为—O（CH2）nO—的基团，其中n表示整数1或2；R8是H、三烷基硅基、F、C1-3烷基、C2-3烯基、C2-3炔基或C1-3烷氧基；R5是C1-10烷基、烯丙基、苯甲基或丙炔基；R6、R7和R8独立地是C1-10烷基、C2-10烯基、C2-10炔基、芳基或—（CH2）NR9基团，其中N在1至10范围内是整数，R9是羟基、烷氧基、氨基、烷基氨基、二烷基氨基、卤素原子、氰基或硝基；R11是烷基或烯基，以及其药学上可接受的盐。
• US6150343A
  申请人：——

  公开号：US6150343A

  公开（公告）日：2000-11-21
• US7514418B2
  申请人：——

  公开号：US7514418B2

  公开（公告）日：2009-04-07
• US7655640B2
  申请人：——

  公开号：US7655640B2

  公开（公告）日：2010-02-02
• A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles
  作者：Hubert Josien、Sung-Bo Ko、David Bom、Dennis P. Curran

  DOI：10.1002/(sici)1521-3765(199801)4:1<67::aid-chem67>3.0.co;2-f

  日期：1998.1

  A general and efficient synthesis of (20S)-camptothecin (1a) is reported. A key common intermediate containing the pyridone and lactone (DE) rings of camptothecin and most derivatives was constructed from 2-trimethylsilyl-6-methoxypyridine by a series of metalation reactions and a Heck cyclization to provide an achiral bicyclic enol ether. Sharpless asymmetric dihydroxylation followed by lactol oxidation and iododesilylation produced the key intermediate in 94% enantiomeric excess. Alkylation with propargyl bromide and a cascade radical reaction with phenyl isonitrile then produced 1a. About 20 other penta- and hexacyclic analogues of camptothecin with differing single or multiple substituents at C7, C9, C10, C11, and/or C12 were made by changing the propargylating agent and the isonitrile. Included among these are several drug candidates and the approved drugs topotecan and irinotecan. The synthesis of the prodrug irinotecan is direct one that does not pass through the active metabolite. The use of ortho-trimethylsilyl-substituted isonitriles allows the regioselective synthesis of camptothecin analogues in cases where isomeric mixtures are formed from the parent isonitriles. The synthesis of the derivatives relies on the broad scope and functional group tolerance of the key cascade radical reaction.