(2S,3aR,7aR)-3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester | 144534-49-6

• 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: (2S,3aR,7aR)-3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester
• 英文别名: (2S,3aR,7aR)-1-benzyl 2-methyl 3a-hydroxy-6-oxo-3,3a,7,7a-tetrahydro-1H-indole-1,2(2H,6H)-dicarboxylate；1-benzyloxy-carbonyl-3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydroindol-2-carboxylate；1-O-benzyl 2-O-methyl (2S,3aR,7aR)-3a-hydroxy-6-oxo-2,3,7,7a-tetrahydroindole-1,2-dicarboxylate
• CAS: 144534-49-6
• 化学式: C₁₈H₁₉NO₆
• 分子量: 345.352
• InChiKey: SKESKQVLOSKZLG-DAYGRLMNSA-N

物化性质

• 沸点：
  528.3±50.0 °C(Predicted)
• 密度：
  1.385±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  93.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,3aR,7aR)-3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester 在 platinum(IV) oxide 吡啶 、 4-二甲氨基吡啶 、 氢气 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 24.0h， 生成 (2S,3aR,7aR)-6-oxo-2,3,3a,4,5,6,7,7a-octahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester
  参考文献：
  名称：

  Total Synthesis and Stereochemical Revision of (+)-Aeruginosin 298-A

  摘要：

  [GRAPHICS]Novel routes toward both enantiomers of the bicyclic proline surrogate 2-carboxy-6-hydroxyoctahydroindole, i.e., Choi, were developed on the basis of the oxidative cyclization of L-tyrosine. Synthesis of the proposed sequence of (+)-aeruginosin 298-A did not provide the natural product. Incorporation of a D-leucine residue, in contrast, led to the total synthesis of this thrombin inhibitor.

  DOI：

  10.1021/ol006759x
• 作为产物：
  描述：

  (2S,3aS,7aR)-1-benzyl 2-methyl 3a-hydroxy-6-oxo-4-(phenylthio)octahydro-1H-indole-1,2-dicarboxylate 在 三乙胺 作用下， 以 二氯甲烷-D2 为溶剂， 生成 (2S,3aR,7aR)-3a-hydroxy-6-oxo-2,3,3a,6,7,7a-hexahydroindole-1,2-dicarboxylic acid 1-benzyl ester 2-methyl ester
  参考文献：
  名称：

  Influence of Base and Structure in the Reversible Covalent Conjugate Addition of Thiol to Polycyclic Enone Scaffolds

  摘要：

  The energetics of thiol addition and elimination reactions to bicyclic enones derived from an indole core structure were explored using H-1 NMR and density functional theory (DFT) calculations. The agreement between experiment and theory is excellent, and the combined results reveal that even minor changes in the conformation of the enone, substituents on the scaffold, and the use of different bases have a signficant influence on product distribution. A potential application of these principles is in the rational design of new reversible covalent enzyme inhibitors.

  DOI：

  10.1021/ol400094k

文献信息

• Studies on the synthesis of Stemona alkaloids; stereoselective preparation of the hydroindole ring system by oxidative cyclization of tyrosine
  作者：Peter Wipf、Yuntae Kim

  DOI：10.1016/s0040-4039(00)61121-8

  日期：1992.9

  The core hydroindole ring system of the Stemona alkaloids was prepared by oxidation of tyrosine with a hypervalent iodine reagent followed by a diastereotopic group-selective intramolecular conjugate addition. Further transformations illustrate the versatility of the highly functionalized hydroindolenone 3 for alkaloid synthesis.

  Stemona生物碱的核心氢吲哚环系是通过用高价碘试剂氧化酪氨酸，然后添加非对映异构基团选择性分子内共轭物来制备的。进一步的转化说明了高度官能化的氢化吲哚酮3在生物碱合成中的多功能性。
• Radical cleavage of a β-hydroxy azide: a reversal of regioselectivity in the oxidative fragmentation of hydroindoles
  作者：Peter Wipf、David A. Mareska

  DOI：10.1016/s0040-4039(00)00706-1

  日期：2000.6

  Treatment of hydroindole 17 with PhI(OAc)2/I2 leads to oxidative fragmentation of the β-hydroxy azide moiety and results in the exclusive formation of keto nitrile 18 via radical cleavage of the lateral ring C–C bond.

  用PhI（OAc）2 / I 2处理氢吲哚17会导致β-羟基叠氮化物部分的氧化断裂，并通过侧向C-C键的自由基断裂导致酮腈18的排他性形成。
• Asymmetric Total Synthesis of the Stemona Alkaloid (-)-Stenine
  作者：Peter Wipf、Yuntae Kim、David M. Goldstein

  DOI：10.1021/ja00150a010

  日期：1995.11

  Stenine can be extracted from the roots of the Chinese medicinal plant Stemona tuberosa (Stemonaceae), and its structure and absolute configuration were derived by comparison to the major Stemona alkaloid tuberostemonine. We report the first enantioselective total synthesis of (-)-stenine by a strategy that takes advantage of a diastereoselective end-group-differentiating cyclization in the oxidation of L-tyrosine, The resulting cis-fused indolone is converted to the trans-fused core of stenine upon reduction of a pi-allylpalladium complex, and by stereoselective introduction of four additional stereocenters, a butyrolactone and an azepine ring are attached to this alkaloid building block.
• Synthesis of Hydroxylated Bicyclic Amino Acids from <scp>l</scp>-Tyrosine: Octahydro-1<i>H</i>-indole Carboxylates
  作者：Joshua G. Pierce、Dhanalakshmi Kasi、Makoto Fushimi、Anthony Cuzzupe、Peter Wipf

  DOI：10.1021/jo801552j

  日期：2008.10.3

  A stereoselective approach to polyhydroxylated L-Choi derivatives has been developed. The oxidative cyclization Of L-tyrosine was optimized to avoid partial racemization and to allow a more efficient scale-up.
• Asymmetric Total Syntheses of Tuberostemonine, Didehydrotuberostemonine, and 13-Epituberostemonine
  作者：Peter Wipf、Stacey R. Spencer

  DOI：10.1021/ja044280k

  日期：2005.1.1

  Detailed experimental approaches toward the pentacyclic Stemona alkaloids tuberostemonine and didehydrotuberostemonine and the close analogue 13-epituberostemonine are described. The syntheses originate with a hydroindolinone derivative that can be obtained on a large scale in a single step from carbobenzoxy-protected L-tyrosine. Highlights of the conversion of this hydroindolinone to the target structures are the three-fold use of ruthenium catalysts, first in azepine ring-closing metathesis and then in alkene isomerization and cross-metathesis propenyl-vinyl exchange, as well as the stereoselective attachment of a y-butyrolactone ring to a tetracycle core structure by use of a lithiated asymmetric bicyclo[3.2.1]octane (ABO) ortho ester. Structural analysis by density functional theory (DFT) methods revealed that the ease of oxidation of the natural product is likely due to the conformational preferences of the pyrrolidine and the fused cyclohexane rings.