tert-butyl (2-(4-(benzyloxy)-1H-indol-3-yl)ethyl)carbamate | 1520083-65-1

• 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
• 英文名称: tert-butyl (2-(4-(benzyloxy)-1H-indol-3-yl)ethyl)carbamate
• 英文别名: tert-butyl 2-(4-(benzyloxy)-1H-indol-3-yl)ethylcarbamate
• CAS: 1520083-65-1
• 化学式: C₂₂H₂₆N₂O₃
• 分子量: 366.46
• InChiKey: KHCWZGVMOOPKIX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.81
• 重原子数：
  27.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  63.35
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-(4-(benzyloxy)-1H-indol-3-yl)ethyl)carbamate 在 sodium dihydrogenphosphate 、 potassium nitrososulfonate 、 palladium 10% on activated carbon 、 氢气 、 四丁基硫酸氢铵 、 magnesium 、 potassium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 反应 81.0h， 生成 tert-butyl (2-(1,1-dioxido-5,9-dioxo-2,3,4,5,6,9-hexahydro-[1,4]thiazino[2,3-f]indol-8-yl)ethyl)(methyl)carbamate
  参考文献：
  名称：

  Total Synthesis of Thiaplakortone A: Derivatives as Metabolically Stable Leads for the Treatment of Malaria

  摘要：

  Thiaplakortone A (3a), an antimalarial natural product, was prepared by an operationally simple and scalable synthesis. In our efforts to deliver a lead compound with improved potency, metabolic stability, and selectivity, the synthesis was diverted to access a series of analogues. Compounds, 3a-d showed nanomolar activity against the chloroquine-sensitive (3D7) Plasmodium falciparum line and were more active against the chloroquine- and mefloquine-resistant (Dd2) P. falciparum line. All compounds are "Rule-of-5" compliant, and we show that metabolic stability can be enhanced via modification at either the primary or pyrrole nitrogen. These promising results lay the foundation for the development of this structurally unprecedented natural product.

  DOI：

  10.1021/ml400447v
• 作为产物：
  描述：

  4-羟基吲哚 在 potassium carbonate 、 三氯氧磷 作用下， 以 丙酮 为溶剂， 反应 37.17h， 生成 tert-butyl (2-(4-(benzyloxy)-1H-indol-3-yl)ethyl)carbamate
  参考文献：
  名称：

  Total Synthesis of Thiaplakortone A: Derivatives as Metabolically Stable Leads for the Treatment of Malaria

  摘要：

  Thiaplakortone A (3a), an antimalarial natural product, was prepared by an operationally simple and scalable synthesis. In our efforts to deliver a lead compound with improved potency, metabolic stability, and selectivity, the synthesis was diverted to access a series of analogues. Compounds, 3a-d showed nanomolar activity against the chloroquine-sensitive (3D7) Plasmodium falciparum line and were more active against the chloroquine- and mefloquine-resistant (Dd2) P. falciparum line. All compounds are "Rule-of-5" compliant, and we show that metabolic stability can be enhanced via modification at either the primary or pyrrole nitrogen. These promising results lay the foundation for the development of this structurally unprecedented natural product.

  DOI：

  10.1021/ml400447v

文献信息

• Synthesis of polycyclic scaffolds via a gold-catalysed dearomative cyclisation cascade
  作者：Aimee K. Clarke、James A. Rossi-Ashton、Richard J.K. Taylor、William P. Unsworth

  DOI：10.1016/j.tet.2020.131392

  日期：2020.8

  Polycyclic scaffolds found in akuammiline alkaloid natural products can be synthesised from ynone-tethered indoles, via a gold(I)-catalysed dearomative cyclisation cascade sequence. The ynone starting materials are themselves made via a two-step modular synthesis from simple tryptamine and tryptophol derivatives.

  可以通过金（I）催化的脱芳香环化级联序列，从乙炔系拴的吲哚合成在akuammiline生物碱天然产物中发现的多环支架。炔酮原料本身是由两步模块化合成，由简单的色胺和色胺醇衍生物制得。
• Modular Synthesis of Polycyclic Alkaloid Scaffolds via an Enantioselective Dearomative Cascade
  作者：James A. Rossi-Ashton、Aimee K. Clarke、Richard J. K. Taylor、William P. Unsworth

  DOI：10.1021/acs.orglett.0c00053

  日期：2020.2.7

  akuammiline alkaloids can be synthesized from simple tryptamine and tryptophol derivatives via a Ag(I)-catalyzed enantioselective dearomative cyclization cascade sequence. The complex tetracyclic scaffolds are prepared via a rapid, versatile, three-step modular synthesis from simple commercially available indole derivatives in high yields and enantiomeric excess (up to 99% yield and >99% ee).

  akuammiline生物碱的多环核心可以通过Ag（I）催化的对映选择性脱芳香环化级联序列由简单的色胺和色酚合成。复杂的四环支架是通过快速，通用的三步模块化合成方法，由简单的市售吲哚衍生物以高收率和对映体过量（最高收率99％，ee≥99％）制备的。