吡啶并[2,3-d]嘧啶-2,4,7(1H,3H,8H)-三酮,5-叠氮-8-甲基-6-硝基-1,3-二苯基- | 469-23-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 吡啶并[2,3-d]嘧啶-2,4,7(1H,3H,8H)-三酮,5-叠氮-8-甲基-6-硝基-1,3-二苯基-
• 英文名称: d,l-eserethole
• 英文别名: (+/-)-5-ethoxy-1,3a,8-trimethyl-(3ar,8ac)-1,2,3,3a,8,8a-hexahydro-pyrrolo[2,3-b]indole；(+/-)-5-Aethoxy-1,3a,8-trimethyl-(3ar,8ac)-1,2,3,3a,8,8a-hexahydro-pyrrolo[2,3-b]indol；Eserethol；(3aR,8bS)-7-ethoxy-3,4,8b-trimethyl-2,3a-dihydro-1H-pyrrolo[2,3-b]indole
• CAS: 469-23-8
• 化学式: C₁₅H₂₂N₂O
• 分子量: 246.352
• InChiKey: KQWOEHQIZVGMMT-CABCVRRESA-N

物化性质

• 溶解度：
  可溶于氯仿（少量）、乙醇（少量）

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  15.7
• 氢给体数：
  0
• 氢受体数：
  3

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  氧化毒扁豆碱	(+/-)-eseroline	469-22-7	C13H18N2O	218.299

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  氧化毒扁豆碱	(+/-)-eseroline	469-22-7	C13H18N2O	218.299
  [(3aR,8bS)-3,4,8b-三甲基-2,3a-二氢-1H-吡咯并[2,3-b]吲哚-7-基] 3,4-二氢-1H-异喹啉-2-羧酸酯	(3aS,cis)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-yl-3,4-dihydro-2(1H)-isoquinolinecarboxylate	139314-01-5	C23H27N3O2	377.486

反应信息

• 作为反应物：
  描述：

  吡啶并[2,3-d]嘧啶-2,4,7(1H,3H,8H)-三酮,5-叠氮-8-甲基-6-硝基-1,3-二苯基- 在 氢溴酸 、 lithium bromide 作用下， 反应 5.0h， 以95.0%的产率得到氧化毒扁豆碱
  参考文献：
  名称：

  合成（3a s，cis）-1,2,3,3a，8,8a-hexahydro-1,3a，8-trimethylpyrrolo [2,3 - b ] indol -5-yl的有效O-脱烷基方法-3,4-二氢-2（1 H）-异喹啉羧酸酯

  摘要：

  作为关键步骤，通过溴化锂催化的氢溴酸O-脱烷基化方法，从（-）-乙二醛（2a）以高收率和高纯度合成标题化合物。

  DOI：

  10.1002/jhet.5570370216
• 作为产物：
  描述：

  氧化毒扁豆碱 在 sodium ethanolate 、 对甲苯磺酸乙酯 作用下， 生成 吡啶并[2,3-d]嘧啶-2,4,7(1H,3H,8H)-三酮,5-叠氮-8-甲基-6-硝基-1,3-二苯基-
  参考文献：
  名称：

  羟色胺。第二部分 毒扁豆碱的新合成

  摘要：

  DOI：

  10.1039/jr9540003651

文献信息

• Alkaloid synthesis via the intramolecular imidate methylide 1,3-dipolar cycloaddition reaction
  作者：Richard Smith、Tom Livinghouse

  DOI：10.1016/s0040-4020(01)96709-2

  日期：1985.1

  A concise synthesis for the neurotoxic physostigmine alkaloid d,l-eserethole is described which relys upon an intramolecular cycloaddition reaction involving a “non-stabilized” imidate methylide and an unactivated alkene. The facility of this cyclization is enhanced by the rigid alignment inforced upon the dipole and dipolarophile by their ortho-disposition on an aryl nucleus. The synthetic limitations

  描述了神经毒性的毒扁豆碱生物碱d，1-塞孔的简明合成，其依赖于分子内环加成反应，该反应涉及“未稳定的”亚氨酸酯亚甲基和未活化的烯烃。通过偶合和偶极亲和体在芳基核上的邻位排列加强的刚性排列，增强了这种环化的便利性。在尝试合成赤藓骨架的过程中揭示了这种环形方法的合成局限性。在这种情况下，亚胺酸酯亚甲基的质子性重排为异构烯胺，从而排除了所需的环化反应。
• Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and)
  申请人：Hoechst-Roussel Pharmaceuticals, Inc.

  公开号：US04791107A1

  公开（公告）日：1988-12-13

  There are described compounds of the formula ##STR1## where (a) X is O or S; (b) R is H, loweralkyl, ##STR2## where Y is O or S; R.sub.2 is alkyl, cycloalkyl, bicycloalkyl, cycloalkenyl, aryl, arylloweralkyl, heteroaryl or heteroarylloweralkyl, R.sub.3 is H or alkyl, or the group --NR.sub.2 R.sub.3 taken as a whole is 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 4-thiomorpholinyl, 1-piperazinyl, 4-methyl-1-piperazinyl or 2-(2,6-dichlorophenylimino)-1-imidazolidinyl) and R.sub.4 is hydrogen, loweralkyl, arylloweralkyl, diarylloweralkyl, aryl or heteroaryl, (c) m is 1 or 2; (d) each Z is independently H, loweralkyl, halogen, nitro, --NH.sub.2, loweralkylcarbonylamino, arylcarbonylamino, loweralkoxycarbonylamino or loweralkylamino, and (e) R.sub.1 is H, loweralkyl, arylloweralkyl, heteroarylloweralkyl, cycloalkylmethyl or loweralkenylmethyl, with the proviso that when X is O, m is 1, Z is H and R.sub.1 is methyl, R is not --CONHCH.sub.3, --CONHC.sub.6 H.sub.5, hydrogen, methyl or ethyl, and that when X is O, m is 1 and Z and R.sub.1 are both hydrogen, R is not hydrogen or methyl, and pharmaceutically acceptable acid addition salts thereof which are useful as memory-enhancing and analgesic agents.

  描述了以下化合物的化学式##STR1## 其中（a）X为O或S；（b）R为H、loweralkyl、##STR2## 其中Y为O或S；R.sub.2为烷基、环烷基、双环烷基、环烯基、芳基、芳基loweralkyl、杂环芳基或杂环芳基loweralkyl，R.sub.3为H或烷基，或整体视为--NR.sub.2 R.sub.3时为1-吡咯基、1-哌啶基、4-吗啉基、4-硫代吗啉基、1-哌嗪基、4-甲基-1-哌嗪基或2-(2,6-二氯苯基亚胺基)-1-咪唑烷基）和R.sub.4为氢、loweralkyl、芳基loweralkyl、二芳基loweralkyl、芳基或杂环芳基，（c）m为1或2；（d）每个Z独立地为H、loweralkyl、卤素、硝基、--NH.sub.2、loweralkylcarbonylamino、arylcarbonylamino、loweralkoxycarbonylamino或loweralkylamino，（e）R.sub.1为H、loweralkyl、芳基loweralkyl、杂环芳基loweralkyl、环烷基甲基或loweralkenylmethyl，但当X为O时，m为1、Z为H且R.sub.1为甲基时，R不是--CONHCH.sub.3、--CONHC.sub.6 H.sub.5、氢、甲基或乙基，当X为O时，m为1且Z和R.sub.1均为氢时，R不是氢或甲基，以及其药用可接受的酸盐，可用作增强记忆和镇痛剂。
• A Formal Asymmetric Synthesis of Calabar Bean Alkaloids.
  作者：Manabu NODE、Xiao-jiang HAO、Kiyoharu NISHIDE、Kaoru FUJI

  DOI：10.1248/cpb.44.715

  日期：——

  A total synthesis of (-)-eserethole (2) has been accomplished using the Diels-Alder reaction of (S)-(-)-2-methyl-2-[2-(E)-nitroethenyl]-δ-valerolactone (3) and Danishefsky's diene as a key step. The synthesis of optically pure (-)-eserethole (2) constitutes a formal synthesis of naturaly occurring Calabar bean alkaloids, such as (-)-physostigmine (1), (-)-physovenine (17) and (-)-geneserine (18).

  (-)-eserethole (2) 的全合成已经完成，其中关键步骤是利用(S)-(-)-2-甲基-2-[2-(E)-硝基乙烯基]-δ-戊内酯(3)与Danishefsky's二烯的Diels-Alder反应。光学纯(-)-eserethole (2)的合成构成了卡拉巴豆生物碱如(-)-physostigmine (1)、(-)-physovenine (17)和(-)-geneserine (18)的形式合成。
• Memory enhancing and analgesic 1,2,3a,8,8a-hexahydro-3a,8(and
  申请人：Hoechst-Roussel Pharmaceuticals Inc.

  公开号：US05187165A1

  公开（公告）日：1993-02-16

  There are disclosed various derivatives of eseroline and related compounds of the formula below ##STR1## where R,R.sub.1, X,Z and m are as defined in the specification, which compounds being useful for enhancing cholinergic function, as antidepressant agents and as analgesic agents.

  下面公式的eseroline和相关化合物的各种衍生物已经被披露，其中R、R.sub.1、X、Z和m如规范中定义，这些化合物可用于增强胆碱能功能，作为抗抑郁剂和镇痛剂。
• Method for preparing 1, 2, 3, 3A, 8, 8A-hexahydro-3A, 8 (and 1, 3A,
  申请人：Hoechst Marion Roussel, Inc.

  公开号：US05621114A1

  公开（公告）日：1997-04-15

  There are described compounds of the formula ##STR1## where (a) X is O or S; (b) R is H, loweralkyl, ##STR2## where Y is O or S; R.sub.2 is alkyl, cycloalkyl, bicycloalkyl, cycloalkenyl, aryl, arylloweralkyl, heteroaryl or heteroarylloweralkyl, R.sub.3 is H or alkyl, or the group --NR.sub.2 R.sub.3 taken as a whole is 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, 4-thiomorpholinyl, 1-piperazinyl, 4-methyl-1-piperazinyl or 2-(2,6-dichlorophenylimino)-1-imidazolidinyl) and R.sub.4 is hydrogen, loweralkyl, arylloweralkyl, diarylloweralkyl, aryl or heteroaryl, (c) m is 1 or 2; (d) each Z is independently H, loweralkyl, halogen, nitro, --NH.sub.2, loweralkylcarbonylamino, arylcarbonylamino, loweralkoxycarbonylamino or loweralkylamino, and (e) R.sub.1 is H, loweralkyl, arylloweralkyl, heteroarylloweralkyl, cycloalkylmethyl or loweralkenylmethyl, with the proviso that when X is O, m is 1, Z is H and R.sub.1 is methyl, R is not --CONHCH.sub.3, --CONHC.sub.6 H.sub.5, hydrogen, methyl or ethyl, and that when X is O, m is 1 and Z and R.sub.1 are both hydrogen, R is not hydrogen or methyl, and pharmaceutically acceptable acid addition salts thereof which are useful as memory-enhancing and analgesic agents.

  描述了一种化合物的公式 ##STR1## 其中：(a) X为O或S; (b) R为H、低烷基、##STR2## 其中Y为O或S; R.sub.2为烷基、环烷基、双环烷基、环烯基、芳基、芳基低烷基、杂环芳基或杂环芳基低烷基，R.sub.3为H或烷基，或作为整体的--NR.sub.2R.sub.3为1-吡咯基、1-哌啶基、4-吗啉基、4-硫代吗啉基、1-哌嗪基、4-甲基-1-哌嗪基或2-(2,6-二氯苯基亚氨基)-1-咪唑啉基)，R.sub.4为氢、低烷基、芳基低烷基、二芳基低烷基、芳基或杂环芳基，(c) m为1或2；(d) 每个Z独立地为H、低烷基、卤素、硝基、--NH.sub.2、低烷基羰基氨基、芳基羰基氨基、低烷氧羰基氨基或低烷基氨基；(e) R.sub.1为H、低烷基、芳基低烷基、杂环芳基低烷基、环烷基甲基或低烯基甲基，但当X为O、m为1、Z为H且R.sub.1为甲基时，R不为--CONHCH.sub.3、--CONHC.sub.6H.sub.5、氢、甲基或乙基；当X为O、m为1且Z和R.sub.1都为氢时，R不为氢或甲基。它们的药物可接受的酸盐可用作记忆增强和镇痛剂。