(3S,8S,9R)-3-(tert-butyldiphenylsilanyloxymethyl)-8-methoxyhexahydroindolizin-5-one | 743423-44-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: (3S,8S,9R)-3-(tert-butyldiphenylsilanyloxymethyl)-8-methoxyhexahydroindolizin-5-one
• 英文别名: (3S,8S,8aS)-3-[[tert-butyl(diphenyl)silyl]oxymethyl]-8-methoxy-2,3,6,7,8,8a-hexahydro-1H-indolizin-5-one
• CAS: 743423-44-1
• 化学式: C₂₆H₃₅NO₃Si
• 分子量: 437.654
• InChiKey: OOMNXLPZMWOYQR-OYDLWJJNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.73
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,8S,9R)-3-(tert-butyldiphenylsilanyloxymethyl)-8-methoxyhexahydroindolizin-5-one 在 palladium on activated charcoal 吡啶 、 N-甲基吡咯烷酮 、 盐酸 、 4-二甲氨基吡啶 、 sodium dihydrogenphosphate 、 四丙基高钌酸铵 、 Davis achiral oxaziridine 、 sodium perchlorate 、 四丁基氟化铵 、 氢气 、 叔丁基锂 、 sodium methylate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 叔丁醇 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 生成 (3S,6S,8S,8aS)-6-Benzyl-6-hydroxy-8-methoxy-5-oxo-octahydro-indolizine-3-carboxylic acid 4-carbamimidoyl-benzylamide; hydrochloride
  参考文献：
  名称：

  Exploring the chiral space within the active site of α-thrombin with a constrained mimic of d -Phe-Pro-Arg — design, synthesis, inhibitory activity, and X-ray structure of an enzyme–inhibitor complex

  摘要：

  An indolizidinone motif with strategically placed substitutents was designed and synthesized as a constrained mimic of D-Phe-Pro-Arg. Low nanomolar inhibition of a-thrombin validates the design elements in this inhibitor which also exhibits a 20-fold selectivity for thrombin versus trypsin. An X-ray crystal structure of the inhibitor with alpha-thrombin shows the expected interactions with key amino acids within the active site and some notable changes in positions. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00669-1
• 作为产物：
  描述：

  (3S,9S)-5-oxo-1,2,3,5,6,8a-hexahydroindolizine-3-carboxylic acid 在 palladium on activated charcoal 咪唑 、 sodium tetrahydroborate 、 urea-hydrogen peroxide 、 氢气 、 potassium hydride 、 三乙胺 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.42h， 生成 (3S,8S,9R)-3-(tert-butyldiphenylsilanyloxymethyl)-8-methoxyhexahydroindolizin-5-one
  参考文献：
  名称：

  Hanessian, Stephen; Sailes, Helen; Munro, Alexander, Journal of Organic Chemistry, 2003, vol. 68, # 19, p. 7219 - 7233

  摘要：

  DOI：

文献信息

• Synthesis of 3₁₀-Helix-Inducing Constrained Analogues of <scp>l</scp>-Proline
  作者：Stephen Hanessian、Gianluca Papeo、Kamal Fettis、Eric Therrien、Minh Tan Phan Viet

  DOI：10.1021/jo0401422

  日期：2004.7.1

  A bicyclic indolizidinone carboxylic acid and a tricyclic constrained analogue Of L-proline were synthesized and evaluated for their ability to induce helix formation as L-Ala tetrapeptides. Variable-temperature NMR, DMSO titration, CD spectra, and X-ray structure analyses, in conjunction with molecular modeling, confirmed the existence of 3(10)-helical motifs with di- and tetrapeptides Of L-Ala.
• Hanessian, Stephen; Sailes, Helen; Munro, Alexander, Journal of Organic Chemistry, 2003, vol. 68, # 19, p. 7219 - 7233
  作者：Hanessian, Stephen、Sailes, Helen、Munro, Alexander、Therrien, Eric

  DOI：——

  日期：——
• Exploring the chiral space within the active site of α-thrombin with a constrained mimic of d -Phe-Pro-Arg — design, synthesis, inhibitory activity, and X-ray structure of an enzyme–inhibitor complex
  作者：Stephen Hanessian、Elise Balaux、Djorde Musil、Lise-Lotte Olsson、Ingemar Nilsson

  DOI：10.1016/s0960-894x(99)00669-1

  日期：2000.2

  An indolizidinone motif with strategically placed substitutents was designed and synthesized as a constrained mimic of D-Phe-Pro-Arg. Low nanomolar inhibition of a-thrombin validates the design elements in this inhibitor which also exhibits a 20-fold selectivity for thrombin versus trypsin. An X-ray crystal structure of the inhibitor with alpha-thrombin shows the expected interactions with key amino acids within the active site and some notable changes in positions. (C) 2000 Elsevier Science Ltd. All rights reserved.