甲基5-氧代-1,2,3,5-四氢-8-吲嗪羧酸酯 | 87286-02-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 中文名称: 甲基5-氧代-1,2,3,5-四氢-8-吲嗪羧酸酯
• 英文名称: methyl 5-oxo-1,2,3,5-tetrahydroindolizine-8-carboxylate
• 英文别名: methyl 5-oxo-2,3-dihydro-1H-indolizine-8-carboxylate
• CAS: 87286-02-0
• 化学式: C₁₀H₁₁NO₃
• mdl: MFCD09879432
• 分子量: 193.202
• InChiKey: OHDXOCXOFHYAAT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  甲基5-氧代-1,2,3,5-四氢-8-吲嗪羧酸酯 在 platinum(IV) oxide lithium aluminium tetrahydride 、 氢溴酸 、 氢气 作用下， 以 四氢呋喃 、 溶剂黄146 为溶剂， 135.0 ℃ 、620.53 kPa 条件下， 反应 29.0h， 生成 八氢吲嗪
  参考文献：
  名称：

  An Isomünchnone-Based Method for the Synthesis of Highly Substituted 2(1H)-Pyridones

  摘要：

  1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p-acetamidobenzenesulfonyl azide and triethylamine. Treatment; of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomunchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1H)-pyridone ring system. The 3-hydroxy-2(1H)-pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (+/-)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (-)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh-2(OAc)(4) in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.

  DOI：

  10.1021/jo9911600
• 作为产物：
  描述：

  1-(2-benzenesulfonyl-2-diazoacetyl)pyrrolidin-2-one 在 rhodium(II) acetate dimer 、 甲酸 、 bis(triphenylphosphine) palladium (Il) acetate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 23.0h， 生成 甲基5-氧代-1,2,3,5-四氢-8-吲嗪羧酸酯
  参考文献：
  名称：

  An Isomünchnone-Based Method for the Synthesis of Highly Substituted 2(1H)-Pyridones

  摘要：

  1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p-acetamidobenzenesulfonyl azide and triethylamine. Treatment; of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomunchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1H)-pyridone ring system. The 3-hydroxy-2(1H)-pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (+/-)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (-)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh-2(OAc)(4) in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.

  DOI：

  10.1021/jo9911600

文献信息

• Design, synthesis and cytotoxicity of the antitumor agent 1-azabicycles for chemoresistant glioblastoma cells
  作者：Mona Oliveira、Lourenço Luis Botelho de Santana、José Claudio Serafim、Airam Oliveira Santos、Michelle Pereira Quintino、José Tiago Menezes Correia、Fabiano Damasceno、José Ricardo Sabino、Thiago Rubens Cardim Pires、Paulo Lucas Cerqueira Coelho、Giselle Pinto de Faria Lopes、Henning Ulrich、Silvia Lima Costa、Silvio Cunha

  DOI：10.1007/s10637-019-00877-2

  日期：2020.10

  Twelve multi-functional pyrrolizidinones, indolizidinones and pyrroliazepinones were prepared from formal aza-[3 + 2] and aza-[3 + 3] cycloadditions of five- to seven-membered heterocyclic enaminones as diverse ambident electrophiles. The antitumor activity of these alkaloid-like compounds was investigated through an initial screening performed on human glioblastoma multiform (GBM) cell lines (GL-15, U251), on murine glioma cells line (C6) and on normal glial cells. Of the compounds tested, the new pyrrolo[1,2a]azepinone, [ethyl (3-oxo-1,2-diphenyl-6,7,8,9-tetrahydro-3H-pyrrolo[1,2a]azepin-9a(5H)-yl)acetate] or (Compound-13) exhibited selective cytotoxic effects on GBM-temozolomide resistant cells. Compound-13 exerted dose-dependent cytotoxic activity by promoting arrest of cells in the G0/G1 phase of the cell cycle in the first 24 h. The apoptotic effect observed was in a time-dependent manner. Anti-migratory effect promoted by the treatment with compound-13 was also observed. Moreover, healthy mixed glial cell cultures from rat brain exhibited no cytotoxicity effect upon exposure to compound-13. Thus, the present study paves the way for the use of compound-13 as novel antitumor scaffold candidate for glioma cell therapy.

  以五元至七元杂环烯酮作为不同的暧昧亲电体，通过正式的氮杂环合-[3 + 2]和氮杂环合-[3 + 3]环加成反应，制备了 12 种多功能吡咯烷酮、吲哚利嗪酮和吡咯并氮杂卓酮。通过对人类多形性胶质母细胞瘤（GBM）细胞系（GL-15、U251）、鼠胶质瘤细胞系（C6）和正常胶质细胞进行初步筛选，研究了这些生物碱类化合物的抗肿瘤活性。在测试的化合物中，新的吡咯并[1,2a]氮杂环庚酮[(3-氧代-1,2-二苯基-6,7,8,9-四氢-3H-吡咯并[1,2a]氮杂环庚-9a(5H)-基)乙酸乙酯]或（化合物-13）对 GBM-替莫唑胺耐药细胞具有选择性细胞毒性作用。化合物-13 具有剂量依赖性的细胞毒性活性，在细胞周期的前 24 h 促进细胞停滞在 G0/G1 期。观察到的凋亡效应与时间有关。化合物-13 还具有抗迁移作用。此外，来自大鼠大脑的健康混合胶质细胞培养物在暴露于化合物-13 后没有表现出细胞毒性效应。因此，本研究为将化合物-13 用作胶质瘤细胞治疗的新型抗肿瘤支架候选物铺平了道路。
• Nagasaka, Tatsuo; Inoue, Hitoshi; Hamaguchi, Fumiko, Heterocycles, 1983, vol. 20, # 6, p. 1099 - 1107
  作者：Nagasaka, Tatsuo、Inoue, Hitoshi、Hamaguchi, Fumiko

  DOI：——

  日期：——
• NAGASAKA, TATSUO;INOUE, HITOSHI;HAMAGUCHI, FUMIKO, HETEROCYCLES, 1983, 20, N 6, 1099-1107
  作者：NAGASAKA, TATSUO、INOUE, HITOSHI、HAMAGUCHI, FUMIKO

  DOI：——

  日期：——
• An Isomünchnone-Based Method for the Synthesis of Highly Substituted 2(1<i>H</i>)-Pyridones
  作者：Albert Padwa、Scott M. Sheehan、Christopher S. Straub

  DOI：10.1021/jo9911600

  日期：1999.11.1

  1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p-acetamidobenzenesulfonyl azide and triethylamine. Treatment; of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomunchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1H)-pyridone ring system. The 3-hydroxy-2(1H)-pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (+/-)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (-)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomunchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh-2(OAc)(4) in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.