(S)-1-Isobutyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester | 259526-94-8

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (S)-1-Isobutyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester
• CAS: 259526-94-8
• 化学式: C₁₇H₂₂N₂O₂
• 分子量: 286.374
• InChiKey: LFBDUYMSBJXRJJ-LOACHALJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  54.12
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-1-Isobutyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 生成 3-(Methoxycarbonyl)-1-(2-methylpropyl)-β-carboline
  参考文献：
  名称：

  A β-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer

  摘要：

  DOI：

  10.1021/acs.jmedchem.4c00030
• 作为产物：
  描述：

  L-色氨酸 在 氯化亚砜 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 27.0h， 生成 (S)-1-Isobutyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester
  参考文献：
  名称：

  A β-Carboline Derivate PAD4 Inhibitor Reshapes Neutrophil Phenotype and Improves the Tumor Immune Microenvironment against Triple-Negative Breast Cancer

  摘要：

  DOI：

  10.1021/acs.jmedchem.4c00030

文献信息

• Synthesis and ABCG2 Inhibitory Activity of Novel Fumitremorgin C Analogs – Specificity and Structure Activity Correlations
  作者：Orsolya Szolomajer-Csikos、Erzsebet Beery、Levente Kosa、Zsuzsanna Rajnai、Marton Jani、Anasztazia Hetenyi、Katalin Tauber Jakab、Peter Krajcsi、Gabor K Toth

  DOI：10.2174/1573406411309040003

  日期：2013.4.1

  The Ko family of fumitremorgin C analogs are potent and selective ABCG2 inhibitors. However, the most potent Ko compounds carry an ester linkage in their side-chain that makes them chemically and metabolically less stable. We have synthesized 16 tricyclic and 28 tetracyclic novel analogs devoid of ester linkages and tested them for ABCG2 inhibition potency and specificity. Unlike in the tricyclic analog group, potent ABCG2 inhibitory compounds were found among the tetracyclic analogs. The most potent compounds carried the 3S,6S,12aS configuration. We observed a marked stereospecificity as compounds with the 3S,6S,12aS configuration were at least 18-fold more potent inhibitors than their diastereoisomeric pairs with a 3S,6R,12aS configuration. This stereospecificity was not observed in ABCB1 and ABCC1 inhibition. Therefore, a single chiral center confers specificity for ABCG2 over ABCB1 and ABCC1. This is quite unexpected considering the large multivalent drug binding site these transporters harbor.

  Ko家族的麹霉素C类似物是强效且具有选择性的ABCG2抑制剂。然而，最强的Ko化合物在其侧链中具有酯键，这使得它们在化学和代谢上不太稳定。我们合成了16种三环化合物和28种四环新类似物，这些类似物不含酯键，并对其ABCG2抑制效力和特异性进行了测试。与三环类似物组不同，在四环类似物中发现了强效ABCG2抑制化合物。最强效的化合物具有3S,6S,12aS构型。我们观察到明显的立体特异性，具有3S,6S,12aS构型的化合物至少比具有3S,6R,12aS构型的差向异构体强18倍。这种立体特异性在ABCB1和ABCC1抑制作用中未见。因此，单一的手性中心赋予了ABCG2相对于ABCB1和ABCC1的特异性。考虑到这些转运蛋白具有的大型多价药物结合位点，这是相当意外的。
• The reaction of 3-methylbut-2-enal with tryptamine and its derivatives. A suggestion for the biosynthesis of austamide
  作者：David M. Harrison

  DOI：10.1016/s0040-4039(01)92944-2

  日期：1981.1

  3-methylbut-2-enal furnished the conjugated imine 3b which cyclised with pyridine-tosyl chloride to yield the N-tosyl-tetrahydro-β-carboline 10; alternatively in pH 6.2 aqueous buffer the hydroxyisobutyl derivative 9b was formed. The reaction of L-tryptophan methyl ester with the same aldehyde and the possible biosynthetic relevance of these studies are discussed.

  色胺和3-甲基丁-2-烯醛提供了共轭亚胺3b，其与吡啶-甲苯磺酰氯环化，得到N-甲苯磺酰基-四氢-β-咔啉10; 或者，在pH 6.2的水性缓冲液中，形成了羟基异丁基衍生物9b。讨论了L-色氨酸甲酯与相同醛的反应以及这些研究可能的生物合成相关性。
• A Biomimetic Total Synthesis of (−)-Spirotryprostatin B and Related Studies
  作者：Haishan Wang、A. Ganesan

  DOI：10.1021/jo000306o

  日期：2000.7.1

  rearrangement of the indole to form a spirooxindole. Synthetically, formation of the oxindole ring was stereoselectively accomplished by reaction of the appropriate indole precursor with N-bromosuccinimide. For optimum results, the oxidation should be carried out prior to diketopiperazine cyclization. In this manner, we have synthesized the tetrahydro- and dihydro- analogues of spirotryprostatin B in four steps

  得自Trp-Pro二酮哌嗪的异戊烯化的天然产物螺旋菌前列腺素A和B也具有吲哚的氧化重排以形成螺环吲哚的特征。合成地，通过适当的吲哚前体与N-溴代琥珀酰亚胺的反应立体选择性地完成羟吲哚环的形成。为了获得最佳结果，应在二酮哌嗪环化之前进行氧化。通过这种方式，我们从L-色氨酸甲酯的四个步骤中合成了螺旋菌前列腺素B的四氢和二氢类似物。然后，通过使吡咯烷环不饱和成吡咯啉，将二氢衍生物转化为螺菌素前列腺素B，从而明确确认了天然产物的结构。