(4aR,12R)-2,3,4,4abeta,5,6,7,10-八氢-1,12-二甲基-1H-5beta,10bbeta-丙桥-1,7-菲罗啉-8(9H)-酮 | 596-55-4

• 物质功能分类: 分析化学 - 标准品 - 中药标准品
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: (4aR,12R)-2,3,4,4abeta,5,6,7,10-八氢-1,12-二甲基-1H-5beta,10bbeta-丙桥-1,7-菲罗啉-8(9H)-酮
• 中文别名: (4AR,12R)-2,3,4,4ABETA,5,6,7,10-八氢-1,12-二甲基-1H-5BETA,10BBETA-丙桥-1,7-菲罗啉-8(9H)-酮
• 英文名称: α-obscurine
• 英文别名: alpha-Obscurine；(1R,9S,10R,16R)-14,16-dimethyl-6,14-diazatetracyclo[7.5.3.01,10.02,7]heptadec-2(7)-en-5-one
• CAS: 596-55-4
• 化学式: C₁₇H₂₆N₂O
• 分子量: 274.406
• InChiKey: HXJHQEWSHQXRPH-IPJQOSJUSA-N

物化性质

• 熔点：
  283-284 °C(Solv: methanol (67-56-1))
• 沸点：
  471.1±45.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  20
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4aR,12R)-2,3,4,4abeta,5,6,7,10-八氢-1,12-二甲基-1H-5beta,10bbeta-丙桥-1,7-菲罗啉-8(9H)-酮 在 碘苯二乙酸 、 碘 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.75h， 以62%的产率得到
  参考文献：
  名称：

  PIDA/I₂-Mediated α- and β-C(sp³)–H Bond Dual Functionalization of Tertiary Amines

  摘要：

  The alpha,beta-C(sp(3))-H bond dual functionalization of tertiary amines is still a challenging task for both organic and medicinal chemists. Herein a direct, mild, metal-free, and site-specific method mediated by PIDA/I-2 was developed for alpha,beta-C(sp(3))-H bond dual functionalization of tertiary amines, and this method can provide facile access to alpha-keto lactams or rarely studied alpha,alpha-diiodo lactams. Moreover, this method was used for the effective syntheses of three natural products [obscurumine C (13), obscurumine O (17), and strychnocarpine (18)] and direct preparation of mimics of the in vivo metabolites of two FDA-approved drugs (imatinib and donepezil) in 36-60% overall yield. The method represents a promising protocol for the late-stage alpha,beta-C(sp(3))-H bond oxidative dual functionalization of tertiary amine-containing drugs and complex natural products.

  DOI：

  10.1021/acs.joc.8b01424

文献信息

• Discovery of <i>α</i>‐Obscurine Derivatives as Novel Ca_v3.1 Calcium Channel Blockers
  作者：Lei Wang、Wen‐Yan Li、Zai‐Feng Yuan、Qin‐Shi Zhao

  DOI：10.1002/cbdv.202400182

  日期：2024.4

  MK8998, none are currently available on the market. This study investigates the efficacy of Lycopodium alkaloids, particularly as natural product-based TTCC blockers. We synthesized eighteen derivatives from α-obscurine, a lycodine-type alkaloid, and identified five derivatives with significant Cav3.1 blockade activity. The most potent derivative, compound 7, exhibited an IC50 value of 0.19±0.03 μM and

  电压门控钙通道 (VGCC)，特别是 T 型钙通道 (TTCC)，对于各种生理过程至关重要，并且与疼痛、癫痫和癌症有关。尽管 Z944 和 MK8998 等 TTCC 阻滞剂已进行临床试验，但目前市场上还没有此类药物。本研究调查了石松生物碱的功效，特别是作为基于天然产物的 TTCC 阻滞剂。我们从α -obscurine（一种来可碱型生物碱）合成了 18 种衍生物，并鉴定了 5 种具有显着 Ca v 3.1 阻断活性的衍生物。最有效的衍生物化合物7的 IC 50值为 0.19±0.03 μM，并通过分子对接进行了进一步分析，揭示了与 Ca v 3.1 的关键相互作用。这些发现为 Ca v 3.1 钙通道阻滞剂的结构优化奠定了基础，并将化合物7作为药物开发的有前途的先导化合物和化学生物学研究的工具。
• PIDA/I₂-Mediated α- and β-C(sp³)–H Bond Dual Functionalization of Tertiary Amines
  作者：Yu Zhu、Li-Dong Shao、Zhen-Tao Deng、Ying Bao、Xin Shi、Qin-Shi Zhao

  DOI：10.1021/acs.joc.8b01424

  日期：2018.9.7

  The alpha,beta-C(sp(3))-H bond dual functionalization of tertiary amines is still a challenging task for both organic and medicinal chemists. Herein a direct, mild, metal-free, and site-specific method mediated by PIDA/I-2 was developed for alpha,beta-C(sp(3))-H bond dual functionalization of tertiary amines, and this method can provide facile access to alpha-keto lactams or rarely studied alpha,alpha-diiodo lactams. Moreover, this method was used for the effective syntheses of three natural products [obscurumine C (13), obscurumine O (17), and strychnocarpine (18)] and direct preparation of mimics of the in vivo metabolites of two FDA-approved drugs (imatinib and donepezil) in 36-60% overall yield. The method represents a promising protocol for the late-stage alpha,beta-C(sp(3))-H bond oxidative dual functionalization of tertiary amine-containing drugs and complex natural products.