(3S,6S,8S,8aS)-6-Benzyl-3-(tert-butyl-diphenyl-silanyloxymethyl)-6-hydroxy-8-(4-methoxy-benzyloxy)-hexahydro-indolizin-5-one | 267661-12-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (3S,6S,8S,8aS)-6-Benzyl-3-(tert-butyl-diphenyl-silanyloxymethyl)-6-hydroxy-8-(4-methoxy-benzyloxy)-hexahydro-indolizin-5-one
• 英文别名: (3S,6S,8S,8aS)-6-benzyl-3-[[tert-butyl(diphenyl)silyl]oxymethyl]-6-hydroxy-8-[(4-methoxyphenyl)methoxy]-1,2,3,7,8,8a-hexahydroindolizin-5-one
• CAS: 267661-12-1
• 化学式: C₄₀H₄₇NO₅Si
• 分子量: 649.902
• InChiKey: BGJHTXREOADFLY-FUVWEXRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.89
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  68.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,6S,8S,8aS)-6-Benzyl-3-(tert-butyl-diphenyl-silanyloxymethyl)-6-hydroxy-8-(4-methoxy-benzyloxy)-hexahydro-indolizin-5-one 在 吡啶 、 二硫化碳 、 4-二甲氨基吡啶 、 四丁基氟化铵 、 sodium hydride 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 碘甲烷 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 0.5h， 生成 Acetic acid (3S,6R,8aS)-6-benzyl-3-hydroxymethyl-5-oxo-octahydro-indolizin-6-yl ester
  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：

  tert-butyl (2S,5S)-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-5-[(2S)-5-oxooxolan-2-yl]pyrrolidine-1-carboxylate 在 Davis' achiral oxaziridine 、 B-溴代邻苯二氧硼烷 、 叔丁基锂 、 sodium methylate 、 四丁基碘化铵 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 (3S,6S,8S,8aS)-6-Benzyl-3-(tert-butyl-diphenyl-silanyloxymethyl)-6-hydroxy-8-(4-methoxy-benzyloxy)-hexahydro-indolizin-5-one
  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

文献信息

• 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.