7-O-tert-butyl 1-O-ethyl (E,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)hept-2-enedioate | 211185-92-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 7-O-tert-butyl 1-O-ethyl (E,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)hept-2-enedioate
• CAS: 211185-92-1
• 化学式: C₂₈H₃₃NO₆
• 分子量: 479.573
• InChiKey: IFUJYIVZAKTCLD-JRJUITNWSA-N

物化性质

• 沸点：
  634.4±55.0 °C(predicted)
• 密度：
  1.158±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  90.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  7-O-tert-butyl 1-O-ethyl (E,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)hept-2-enedioate 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.67h， 生成 ethyl (E,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)-7-(methylamino)-7-oxohept-2-enoate
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 2. Peptide Structure−Activity Studies

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s(-1) and antiviral EC50's which approach 0.15 mu M. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s(-1)) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 mu M). A 1.9 Angstrom crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-8 3CP is also detailed.

  DOI：

  10.1021/jm9800696
• 作为产物：
  描述：

  Fmoc-O-叔丁基-L-谷氨酸 在 palladium on activated charcoal 三乙基硅烷 、 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 42.25h， 生成 7-O-tert-butyl 1-O-ethyl (E,4S)-4-(9H-fluoren-9-ylmethoxycarbonylamino)hept-2-enedioate
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 2. Peptide Structure−Activity Studies

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various peptide-derived human rhinovirus (HRV) 3C protease (3CP) inhibitors are described. These compounds are comprised of an ethyl propenoate Michael acceptor moiety and a tripeptidyl binding determinant. The systematic modification of each amino acid residue present in the binding determinant as well as the N-terminal functionality is described. Such modifications are shown to provide irreversible HRV-14 3CP inhibitors with anti-3CP activities (k(obs)/[I]) ranging from 60 to 280 000 M-1 s(-1) and antiviral EC50's which approach 0.15 mu M. An optimized inhibitor which incorporates several improvements identified by the structure-activity studies is also described. This molecule displays very rapid irreversible inhibition of HRV-14 3CP (k(obs)/[I] = 800 000 M-1 s(-1)) and potent antiviral activity against HRV-14 in cell culture (EC50 = 0.056 mu M). A 1.9 Angstrom crystal structure of an S-alkylthiocarbamate-containing inhibitor complexed with HRV-8 3CP is also detailed.

  DOI：

  10.1021/jm9800696

文献信息

• Synthesis of Orthogonally Protected (2R,3R,4S)-4-Amino-2,3-dihydroxyheptane-1,7-dioic Acid
  作者：Hiroyuki Konno、Yoshinori Tokairin、Kakeru Maita、Sho Takeda

  DOI：10.1055/s-0034-1378902

  日期：——

  (2R, 3R, 4S)-4-Amino-2,3-dihydroxyheptane-1,7-dioic acid, a common component of cyclic depsipeptide homophymines with anti-HIV activity, was synthesized as its orthogonally protected derivative from Fmoc-Glu(t-Bu)-OH in 6 steps. Osmium-catalyzed dihydroxylation of.-amino-Z-alpha, beta-unsaturated esters gave the dihydroxy esters with moderate diastereoselectivity. The stereochemistries of the amino acids were determined by comparison of H-1 NMR spectra.

  （2R, 3R, 4S）-4-氨基-2,3-二羟基庚酸-1,7-二甲酸是一种具有抗HIV活性的环状 depsipeptide homophymines的常见成分，本文通过6步合成，将其正交保护衍生物由 Fmoc-Glu(t-Bu)-OH 制得。通过锇催化的-氨基-Z-α,β-不饱和酯的二羟基化反应，得到具有中等非对映选择性的二羟基酯。氨基酸的立体化学通过比较 H-1 NMR �谱图确定。