2-氨基-3-(6-甲氧基-1H-吲哚-3-基)丙酸甲酯 | 107447-04-1

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 2-氨基-3-(6-甲氧基-1H-吲哚-3-基)丙酸甲酯
• 中文别名: (S)-2-氨基-3-(6-甲氧基-1H-吲哚-3-基)丙酸甲酯
• 英文名称: (S)-methyl 2-amino-3-(6-methoxy-1H-indol-3-yl)propanoate
• 英文别名: methyl (S)-2-amino-3-(6-methoxy-1H-indol-3-yl)propanoate；6-methoxy-L-triptophan methyl ester；6-methoxy-L-tryptophan methyl ester；6-methoxytryptophan methyl ester；methyl (2S)-2-amino-3-(6-methoxy-1H-indol-3-yl)propanoate
• CAS: 107447-04-1
• 化学式: C₁₃H₁₆N₂O₃
• 分子量: 248.282
• InChiKey: KOLLGWLALPFQSZ-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  77.3
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  2-氨基-3-(6-甲氧基-1H-吲哚-3-基)丙酸甲酯 在 N-甲基吗啉 、 四氧化锇 、 三氟化硼乙醚 、 四丁基氟化铵 、 氯化锆(IV) 、 四丁基碘化铵 、 二正丁基氧化锡 、 碳酸氢钠 、 溶剂黄146 、 二乙胺 、 亚硝基苯 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 氯仿 、 水 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 、 叔丁醇 为溶剂， 反应 58.42h， 生成 烟曲酶毒素A
  参考文献：
  名称：

  Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C–H Borylation

  摘要：

  Verruculogen and fumitremorgin A are bioactive alkaloids that contain a unique eight-membered endoperoxide. Although related natural products such as fumitremorgins B and C have been previously synthesized, we report the first synthesis of the more complex, endoperoxide-containing members of this family. A concise route to verruculogen and fumitremorgin A relied not only on a hydroperoxide/indole hemiaminal cyclization, but also on the ability to access the seemingly simple starting material, 6-methoxytryptophan. An iridium-catalyzed C-H borylation/Chan-Lam procedure guided by an N-TIPS group enabled the conversion of a tryptophan derivative into a 6-methoxytryptophan derivative, proving to be a general way to functionalize the C6 position of an N,C3-disubstituted indole for the synthesis of indole-containing natural products and pharmaceuticals.

  DOI：

  10.1021/jacs.5b07154
• 作为产物：
  描述：

  N-[叔丁氧羰基]-L-色氨酸甲酯 在 盐酸 、 1,10-菲罗啉 、 (1,5-cyclooctadiene)(methoxy)iridium(I) dimer 、 四丁基氟化铵 、 联硼酸频那醇酯 、 频那醇硼烷 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 、 水 、 乙酸乙酯 为溶剂， 反应 66.0h， 生成 2-氨基-3-(6-甲氧基-1H-吲哚-3-基)丙酸甲酯
  参考文献：
  名称：

  Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C–H Borylation

  摘要：

  Verruculogen and fumitremorgin A are bioactive alkaloids that contain a unique eight-membered endoperoxide. Although related natural products such as fumitremorgins B and C have been previously synthesized, we report the first synthesis of the more complex, endoperoxide-containing members of this family. A concise route to verruculogen and fumitremorgin A relied not only on a hydroperoxide/indole hemiaminal cyclization, but also on the ability to access the seemingly simple starting material, 6-methoxytryptophan. An iridium-catalyzed C-H borylation/Chan-Lam procedure guided by an N-TIPS group enabled the conversion of a tryptophan derivative into a 6-methoxytryptophan derivative, proving to be a general way to functionalize the C6 position of an N,C3-disubstituted indole for the synthesis of indole-containing natural products and pharmaceuticals.

  DOI：

  10.1021/jacs.5b07154

文献信息

• Total synthesis of (+)-fumitremorgin B, its epimeric isomers, and demethoxy derivatives
  作者：Shin-ichi Kodato、Masako Nakagawa、Mitsuya Hongu、Tomohiko Kawate、Tohru Hino

  DOI：10.1016/s0040-4020(01)85828-2

  日期：1988.1

  Total synthesis of the title compounds is described. The key intermediate, dehydro-pentacyclic 13, is prepared in a sequence involving Pictet-Spengler reaction and DDQ oxidation. The key step in the synthesis was the dihydroxylation of 13 to afford the cis-diol 54, which was performed by direct oxidation with osmium tetroxide, whereas treatment of 13 with N-bromo-succinimide provided the trans-diol

  描述了标题化合物的全合成。关键中间体脱水五环13是按照涉及Pictet-Spengler反应和DDQ氧化的顺序制备的。合成中的关键步骤是将13进行二羟基化，得到顺式二醇54，这是通过用四氧化直接氧化进行的，而用N-溴-琥珀酰亚胺处理13则提供了反式二醇41。 41和54分别给出了13-表-泛泛素B（45）和泛黄素B（1）。13-表-化合物45也通过氧化然后还原而转化为氟莫金B（1）。
• Direct C4-Acetoxylation of Tryptophan and Tryptophan-Containing Peptides <i>via</i> Palladium(II)-Catalyzed C–H Activation
  作者：Qiyu Zhang、Xiong Xie、Jingjing Peng、Feiyang Chen、Jinyu Ma、Chunpu Li、Hong Liu、Dechuan Wang、Jiang Wang

  DOI：10.1021/acs.orglett.1c01434

  日期：2021.6.18

  An efficient regioselective palladium(II)-catalyzed C(sp2)–H 4-acetoxylation of tryptophan and tryptophan-containing peptides is described. This transformation achieves the direct construction of C–O bonds at the tryptophan C4-position and features good functional group tolerance. The 4-hydroxyl compound was obtained by removing acetyl after C4-acetoxylation of tryptophan derivatives and tryptophan-containing

  描述了色氨酸和含色氨酸肽的高效区域选择性钯 （II） 催化的 C（sp2）-H 4-乙酰氧基化。这种转变实现了在色氨酸 C4 位的直接构建 C-O 键，并具有良好的官能团耐受性。色氨酸衍生物和含色氨酸的二肽经 C4-乙酰化后去除乙酰基而得 4-羟基化合物。该方法为合成 4-取代色氨酸衍生物和修饰含色氨酸的肽提供了一种新的策略。
• Total Synthesis of Spirotryprostatin A, Leading to the Discovery of Some Biologically Promising Analogues
  作者：Scott Edmondson、Samuel J. Danishefsky、Laura Sepp-Lorenzino、Neal Rosen

  DOI：10.1021/ja983788i

  日期：1999.3.1

  The total synthesis of the title compound has been accomplished. A key step involves the oxidative rearrangement of the β-carboline derivative to an oxindole via the action of N-bromosuccinimide. From this point, a diketopiperazine was introduced. A thiophenyl group served as a precursor of the isopropylidene function. Implementation of the same sort of chemistry starting with a methoxytryptophan derivative

  标题化合物的全合成已经完成。一个关键步骤涉及通过 N-溴代琥珀酰亚胺的作用将 β-咔啉衍生物氧化重排为羟吲哚。从这一点开始，引入了二酮哌嗪。噻吩基用作异亚丙基官能团的前体。从甲氧基色氨酸衍生物开始实施相同类型的化学反应导致母体结构。此外，已经表明，螺环前列腺素 A 的难以接近的异亚丙基侧链对于生物活性不是必需的。此外，三种缺乏二酮哌嗪系统的类似物被证明作为细胞周期抑制剂非常活跃。
• [EN] INHIBITOR OF BREAST CANCER RESISTANCE PROTEIN (BCRP)<br/>[FR] INHIBITEUR DE PROTÉINE DE RÉSISTANCE DU CANCER DU SEIN (BCRP)
  申请人：MILLENNIUM PHARM INC

  公开号：WO2015054132A1

  公开（公告）日：2015-04-16

  Disclosed are compounds that inhibit breast cancer resistance protein (BCRP), of which compound (I-1), ((3S, 6S, 12aS)-6-isobutyl-9-methoxy-3-methyl-2,3,6,7, 12, 12a- hexahydropyrazino[1',2': 1,6]pyrido[3,4-b]indole-1,4-dione) or a pharmaceutically acceptable salt thereof, and the compound 12, ((3S,6S,12aS)-6-isobutyl-9-methoxy-3,10- dimethyl-2,3,6,7,12, 12a-hexahydropyrazino[ 1',2' : 1,6]pyrido[3,4- b] indole-1,4-dione) or a pharmaceutically acceptable salt thereof. Also disclosed are methods of inhibiting BCRP or decreasing BCRP activity and methods of determining potential BCRP substrates.

  本发明涉及一种抑制乳腺癌抗性蛋白（BCRP）的化合物，其中化合物（I-1）为((3S, 6S, 12aS)-6-异丁基-9-甲氧基-3-甲基-2,3,6,7,12,12a-六氢吡嗪[1',2':1,6]吡啶[3,4-b]吲哚-1,4-二酮)或其药学上可接受的盐，以及化合物12，((3S,6S,12aS)-6-异丁基-9-甲氧基-3,10-二甲基-2,3,6,7,12,12a-六氢吡嗪[1',2':1,6]吡啶[3,4-b]吲哚-1,4-二酮)或其药学上可接受的盐。本发明还涉及抑制BCRP或降低BCRP活性的方法以及确定潜在BCRP底物的方法。
• INHIBITOR OF BREAST CANCER RESISTANCE PROTEIN (BCRP)
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20160214984A1

  公开（公告）日：2016-07-28

  Disclosed are compounds that inhibit breast cancer resistance protein (BCRP), of which compound (I-1), ((3S, 6S, 12aS)-6-isobutyl-9-methoxy-3-methyl-2,3,6,7, 12, 12a- hexahydropyrazino[1′,2′: 1,6]pyrido[3,4-b]indole-1,4-dione) or a pharmaceutically acceptable salt thereof, and the compound 12, ((3S,6S,12aS)-6-isobutyl-9-methoxy-3,10- dimethyl-2,3,6,7,12, 12a-hexahydropyrazino[1′,2′: 1,6]pyrido[3,4- b] indole-1,4-dione) or a pharmaceutically acceptable salt thereof. Also disclosed are methods of inhibiting BCRP or decreasing BCRP activity and methods of determining potential BCRP substrates.

  本发明涉及一种抑制乳腺癌耐药蛋白（BCRP）的化合物，其中化合物（I-1），((3S,6S,12aS)-6-异丁基-9-甲氧基-3-甲基-2,3,6,7,12,12a-六氢吡嗪[1′,2′:1,6]吡啶[3,4-b]吲哚-1,4-二酮)或其药学上可接受的盐，以及化合物12，((3S,6S,12aS)-6-异丁基-9-甲氧基-3,10-二甲基-2,3,6,7,12,12a-六氢吡嗪[1′,2′:1,6]吡啶[3,4-b]吲哚-1,4-二酮)或其药学上可接受的盐。还公开了抑制BCRP或降低BCRP活性的方法，以及确定潜在BCRP基质的方法。