(3S,6R)-3-{(1R)-1-[(3S)-3-hydroxy-1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]ethyl}-6-[(methylsulfanyl)methyl]piperazine-2,5-dione | 165467-67-4

• 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
• 英文名称: (3S,6R)-3-{(1R)-1-[(3S)-3-hydroxy-1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]ethyl}-6-[(methylsulfanyl)methyl]piperazine-2,5-dione
• 英文别名: maremycine A；Maremycin A；(3S,6R)-3-[(1R)-1-[(3S)-3-hydroxy-1-methyl-2-oxoindol-3-yl]ethyl]-6-(methylsulfanylmethyl)piperazine-2,5-dione
• CAS: 165467-67-4
• 化学式: C₁₇H₂₁N₃O₄S
• 分子量: 363.437
• InChiKey: AQJPUORWMCOONW-RDFWBEMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  124
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,6R)-3-{(1R)-1-[(3S)-3-hydroxy-1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]ethyl}-6-[(methylsulfanyl)methyl]piperazine-2,5-dione 在 sodium periodate 作用下， 以 甲醇 、 水 为溶剂， 反应 24.0h， 以96%的产率得到(3S,6R)-3-{(1R)-1-[(3S)-3-hydroxy-1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]ethyl}-6-[(methylsulfinyl)methyl]piperazine-2,5-dione
  参考文献：
  名称：

  Total synthesis of maremycins A, B, C1/C2, D1, and D2

  摘要：

  The total synthesis of maremycins A, B, C-1/C-2, D-1, and D-2 is achieved starting from the natural amino acids L-isoleucine and S-methyl-L-cysteine, in which the total synthesis of maremycins B, C-1/C-2, and D-2 is accomplished for the first time. The synthesis features a position-selective intramolecular bromination process for the synthesis of key chiral building block, a Pd-catalyzed indole synthesis for the preparation of (2S,3S)-beta-methyltryptophan and hydroxylation of oxindoles by molecular oxygen. In addition, the protocol for conversion of maremycins A and B to maremycins C and D was improved. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.11.118
• 作为产物：
  描述：

  (2S,3S)-methyl 3-methyl-2-(2,2,2-trifluoroacetamido)pentanoate 在 吡啶 、 咪唑 、 盐酸 、 甲醇 、 4-二甲氨基吡啶 、 草酰氯 、 acetyl hypobromite 、 pyridine hydrofluoride 、 氧气 、 silica gel 、 silver nitrate 、 溶剂黄146 、 二甲基亚砜 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 、 锌 、 苯酚 作用下， 以 四氢呋喃 、 四氯化碳 、 正己烷 、 二氯甲烷 、 对二甲苯 、 水 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 304.17h， 生成 (3S,6R)-3-{(1R)-1-[(3S)-3-hydroxy-1-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl]ethyl}-6-[(methylsulfanyl)methyl]piperazine-2,5-dione
  参考文献：
  名称：

  Total synthesis of maremycins A, B, C1/C2, D1, and D2

  摘要：

  The total synthesis of maremycins A, B, C-1/C-2, D-1, and D-2 is achieved starting from the natural amino acids L-isoleucine and S-methyl-L-cysteine, in which the total synthesis of maremycins B, C-1/C-2, and D-2 is accomplished for the first time. The synthesis features a position-selective intramolecular bromination process for the synthesis of key chiral building block, a Pd-catalyzed indole synthesis for the preparation of (2S,3S)-beta-methyltryptophan and hydroxylation of oxindoles by molecular oxygen. In addition, the protocol for conversion of maremycins A and B to maremycins C and D was improved. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2011.11.118

文献信息

• Dioxindole in Asymmetric Catalytic Synthesis: Routes to Enantioenriched 3-Substituted 3-Hydroxyoxindoles and the Preparation of Maremycin A
  作者：Giulia Bergonzini、Paolo Melchiorre

  DOI：10.1002/anie.201107443

  日期：2012.1.23

  nucleophilicity of dioxindole under different reaction conditions is key to a direct and easy access to valuable spiro oxindole γ butyrolactones and 3‐substituted 3‐hydroxyoxindole derivatives in excellent yields and enantioselectivities (see scheme). The preparation of maremycin A serves as an example for the potential usefulness of this previously unexplored reactivity in natural product synthesis.

  驯化反应性：了解二恶吲哚在不同反应条件下的亲核性是直接和轻松获得有价值的螺恶二恶唑γ丁内酯和3-取代的3-羟基恶吲哚衍生物的关键，其产率和对映选择性都很高（参见方案）。马雷霉素A的制备可作为这种先前未开发的反应物在天然产物合成中的潜在用途的一个实例。
• Synthesis of tryptophan-containing 2,5-diketopiperazines <i>via</i> sequential C–H activation: total syntheses of tryprostatin A, maremycins A and B
  作者：Xue-Song Yin、Wei-Yi Qi、Bing-Feng Shi

  DOI：10.1039/d1sc02343h

  日期：——

  subsequent C2-selective prenylation of the resulting 6-OMe-Trp by Pd/norbornene-promoted C–H activation led to the total synthesis of tryprostatin A in 12 linear steps from alanine with 25% overall yield. Meanwhile, total syntheses of maremycins A and B were successfully accomplished using a sequential Pd-catalyzed methylene C(sp3)–H methylation as the key step in 15 linear steps from alanine.

  吲哚 2,5-二酮哌嗪 (DKP) 是一种重要的代谢环二肽，含有色氨酸 (Trp) 单元，具有一系列有趣的生物活性。有趣的结构特征和不同的活动激发了对其有效合成的巨大努力。在此，我们报告了通过连续 C-H 激活策略合成三种含 Trp 的 DKP，即胰前列腺素 A 和马雷霉素 A 和 B 的统一策略的开发。关键的色氨酸骨架是通过Pd( II ) 催化的 β-甲基 C(sp 3)–H 单芳基化。随后通过 Pd/降冰片烯促进的 C-H 活化对所得 6-OMe-Trp 进行 C2 选择性异戊二烯化，导致在 12 个线性步骤中从丙氨酸全合成胰前列腺素 A，总产率为 25%。同时，使用连续 Pd 催化的亚甲基 C(sp 3 )-H 甲基化作为来自丙氨酸的 15 个线性步骤中的关键步骤，成功地完成了马雷霉素 A 和 B 的全合成。
• Total Synthesis of Maremycins A and D1 Using Chiral and Cyclic Nitrone with (E)-3-Ethylidene-1-methylindolin-2-one
  作者：Osamu Tamura、Tohru Ueda、Mitsuhide Inada、Nobuyoshi Morita

  DOI：10.3987/com-14-s(k)93

  日期：——

  Total syntheses of maremycin A (4) and maremycin D, (8) were described, featuring 1,3-dipolar cycloaddition of a chiral cyclic nitrone 15 with (E)-3-ethylidene-1-methylindolin-2-one (13). The cycloaddition was reversible, especially at high temperature in the presence of a Lewis acid or in a solvent possessing a high acceptor number. One of the cycloadducts was efficiently led to maremycin A (4) and maremycin D, (8). High optical purity of 4 was confirmed by chiral HPLC comparison with ent-4 prepared from ent-15 and 13.
• Synthesis of Maremycins A and D₁ via Cycloaddition of a Nitrone with (<i>E</i>)-3-Ethylidene-1-methylindolin-2-one
  作者：Tohru Ueda、Mitsuhide Inada、Iwao Okamoto、Nobuyoshi Morita、Osamu Tamura

  DOI：10.1021/ol800515w

  日期：2008.5.1

  A concise synthesis of maremycins A and D-1 has been accomplished via cycloaddition of a chiral cyclic nitrone with (E)-3-ethylidene-1-methylindolin-2-one as a key step. This synthesis clarifies the stereochemistry of the maremycins and is suitable for large-scale synthesis for biological screening.