(3S,8S,9R)-3-(tert-butyldiphenylsilanyloxymethyl)-8-hydroxyhexahydroindolizin-5-one | 181705-72-6

• 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-hydroxyhexahydroindolizin-5-one
• 英文别名: (3S,8S,8aS)-3-[[tert-butyl(diphenyl)silyl]oxymethyl]-8-hydroxy-2,3,6,7,8,8a-hexahydro-1H-indolizin-5-one
• CAS: 181705-72-6
• 化学式: C₂₅H₃₃NO₃Si
• 分子量: 423.627
• InChiKey: MSHITURDQKPBDA-VJBMBRPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.08
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (3S,8S,9R)-3-(tert-butyldiphenylsilanyloxymethyl)-8-hydroxyhexahydroindolizin-5-one 在 palladium on activated charcoal 4-二甲氨基吡啶 、 jones reagent 、 叠氮磷酸二苯酯 、 ammonium acetate 、 氢气 、 双氧水 、 叔丁基锂 、 氧气 、 四丁基碘化铵 、 sodium hydride 、 三乙基硼氢化锂 、 碳酸氢钠 、 氯化铵 、 戴斯-马丁氧化剂 、 氟化氢吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 、 偶氮二甲酸二乙酯 、 三甲氧基磷 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 丙酮 、 乙腈 、 苯 为溶剂， -78.0~70.0 ℃ 、101.33 kPa 条件下， 反应 31.88h， 生成 (3S,6S,8R,8aR)-6-Amino-8-benzyloxy-5-oxo-octahydro-indolizine-3-carboxylic acid 2-trimethylsilanyl-ethyl ester
  参考文献：
  名称：

  A versatile synthesis of a β-turn peptidomimetic scaffold: An approach towards a designed model antagonist of the tachykinin NK-2 receptor

  摘要：

  A general and stereocontrolled synthesis of an azabicyclo[4.3.0] nonane amino acid template with an appended substitutent at C-5 was developed The approach allows for stereochemical and functional variations that extend the utility of these rigid amino acid motifs as peptidomimetics. The synthesis of a weakly active but specific NK-2 receptor antagonist is described. Copyright (C) 1996 Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00275-2
• 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 、 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 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.42h， 生成 (3S,8S,9R)-3-(tert-butyldiphenylsilanyloxymethyl)-8-hydroxyhexahydroindolizin-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

• Lewis Acid Assisted Vinylogous Mannich and Mukaiyama Aldol Reactions: A Route to Densely Hydroxylated Indolizidine Alkaloid Analogues
  作者：Gloria Rassu、Paola Carta、Luigi Pinna、Lucia Battistini、Franca Zanardi、Domenico Acquotti、Giovanni Casiraghi

  DOI：10.1002/(sici)1099-0690(199906)1999:6<1395::aid-ejoc1395>3.0.co;2-t

  日期：1999.6

  The hydroxymethyl-substituted indolizidines 6 and 7, representative members of a ring-B-expanded alexine- australine subclass, are readily accessible by starting with furan-based silyloxydiene 12 and hydroxymethyl hemiaminal 11, through a synthesis sequence involving a scantily exploited vinylogous version of the Mannich reaction. The key iminium electrophilic acceptor 11 is, in turn, available through a vinylogous intermolecular Mukaiyama aldolization process between pyrrole-based silyloxydiene 8 and (S)-glyceraldehyde 9.
• 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.
• 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：——
• A versatile synthesis of a β-turn peptidomimetic scaffold: An approach towards a designed model antagonist of the tachykinin NK-2 receptor
  作者：Stephen Hanessian、Grant McNaughton-Smith

  DOI：10.1016/s0960-894x(96)00275-2

  日期：1996.7

  A general and stereocontrolled synthesis of an azabicyclo[4.3.0] nonane amino acid template with an appended substitutent at C-5 was developed The approach allows for stereochemical and functional variations that extend the utility of these rigid amino acid motifs as peptidomimetics. The synthesis of a weakly active but specific NK-2 receptor antagonist is described. Copyright (C) 1996 Elsevier Science Ltd