(3S)-3-([{(9H-fluoren-9-yl)methoxy}carbonyl]amino)-2-hydroxy-5-methylhexanoic acid

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: (3S)-3-([{(9H-fluoren-9-yl)methoxy}carbonyl]amino)-2-hydroxy-5-methylhexanoic acid
• 英文别名: N-Fmoc-(2S,3S)-3-amino-2-hydroxy-5-methyl-hexanoic acid；(2S,3S)-3-(9H-fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-5-methylhexanoic acid
• 化学式: C₂₂H₂₅NO₅
• 分子量: 383.444
• InChiKey: HZHTWMSZVZTEEL-PMACEKPBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-butyric acid 、 (2S,3S)-3-(9H-Fluoren-9-ylmethoxycarbonylamino)-2-hydroxy-4-methyl-pentanoic acid 、 (3S)-3-([{(9H-fluoren-9-yl)methoxy}carbonyl]amino)-2-hydroxy-5-methylhexanoic acid 生成 H-bAla(2S-OH,3S-iPr)-bAla(2S-OH,3S-Me)-bAla(2S-OH,3S-iBu)-bAla(2S-OH,3S-iPr)-bAla(2S-OH,3S-Me)-bAla(2S-OH,3S-iBu)-NH2
  参考文献：
  名称：

  Chemoenzymatic synthesis of Fmoc-protected (2S,3S)-2-hydroxy-3-amino acids and their application in the synthesis of an α-hydroxylated β-hexapeptide

  摘要：

  A chemoenzymatic, and stereoselective synthesis of Fmoc-protected (2S,3S)-2-hydroxy-3-amino acids from 2-furaldehyde is described as well as their application. without prior hydroxyl protection, in the solid-phase synthesis of a novel completely a-hydroxylated beta -hexapeptide. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00193-8
• 作为产物：
  描述：

  {1-[(S)-(tert-Butyl-dimethyl-silanyloxy)-furan-2-yl-methyl]-3-methyl-butyl}-carbamic acid 9H-fluoren-9-ylmethyl ester 在 臭氧 、 水 作用下， 以 甲醇 、 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 以61%的产率得到(3S)-3-([{(9H-fluoren-9-yl)methoxy}carbonyl]amino)-2-hydroxy-5-methylhexanoic acid
  参考文献：
  名称：

  Chemoenzymatic synthesis of Fmoc-protected (2S,3S)-2-hydroxy-3-amino acids and their application in the synthesis of an α-hydroxylated β-hexapeptide

  摘要：

  A chemoenzymatic, and stereoselective synthesis of Fmoc-protected (2S,3S)-2-hydroxy-3-amino acids from 2-furaldehyde is described as well as their application. without prior hydroxyl protection, in the solid-phase synthesis of a novel completely a-hydroxylated beta -hexapeptide. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00193-8

文献信息

• Evaluation of transition-state mimics in a superior BACE1 cleavage sequence as peptide-mimetic BACE1 inhibitors
  作者：Yasunao Hattori、Kazuya Kobayashi、Ayaka Deguchi、Yukie Nohara、Tomomi Akiyama、Kenta Teruya、Akira Sanjoh、Atsushi Nakagawa、Eiki Yamashita、Kenichi Akaji

  DOI：10.1016/j.bmc.2015.07.023

  日期：2015.9

  A superior substrate sequence for BACE1 containing transition-state mimics at the scissile site was evaluated as a protease inhibitor. Hydroxymethylcarbonyl (HMC) and hydroxyethylamine (HEA) isosteres were selected as the transition state mimics, and incorporated into the scissile site of the superior sequence covering the P4 to P1’ sites (Glu-Ile-Thi-Thi*Nva; *denotes the cleavage site). Isosteres

  易位处含有过渡态模拟物的BACE1的优良底物序列被评估为蛋白酶抑制剂。选择羟甲基羰基（HMC）和羟乙胺（HEA）等位基因作为过渡态模拟物，并将其并入覆盖P 4至P 1 '位的上位序列的易剪位点（Glu-Ile-Thi-Thi * Nva；*表示卵裂位点）。分别合成具有不同的羟基绝对构型的等排体，并评价构型的效果。每个等排异构体的羟基构型均显示出对抑制活性的显着影响。反对-易位部位取代基的构型在HMC型抑制剂中具有有效的抑制活性，而HEA型抑制剂的抗构型则没有抑制活性。基于重组BACE1与每种抑制剂的复合物的X射线晶体学分析进行结构评估，可深入了解蛋白质-配体之间的相互作用，尤其是在主要位点。