(S)-4-Benzylsulfanylcarbonyl-4-(9H-fluoren-9-ylmethoxycarbonylamino)-butyric acid tert-butyl ester | 160002-62-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-4-Benzylsulfanylcarbonyl-4-(9H-fluoren-9-ylmethoxycarbonylamino)-butyric acid tert-butyl ester
• 英文别名: tert-butyl (S)-4-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-5-(benzylthio)-5-oxopentanoate
• CAS: 160002-62-0
• 化学式: C₃₁H₃₃NO₅S
• 分子量: 531.673
• InChiKey: YKXNBELIPKROMY-MHZLTWQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.48
• 重原子数：
  38.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  81.7
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-4-Benzylsulfanylcarbonyl-4-(9H-fluoren-9-ylmethoxycarbonylamino)-butyric acid tert-butyl ester 在 palladium on activated charcoal 三乙基硅烷 作用下， 以 丙酮 为溶剂， 反应 0.25h， 生成 (S)-4-((((9H-芴-9-基)甲氧基)羰基)氨基)-5-氧代戊酸叔丁酯
  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 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 (S)-4-Benzylsulfanylcarbonyl-4-(9H-fluoren-9-ylmethoxycarbonylamino)-butyric acid tert-butyl ester
  参考文献：
  名称：

  Ynamide 介导的硫酯合成

  摘要：

  开发了一种新的 ynamide 介导的硫酯合成策略。重要的是，对于含有 α-手性中心的羧酸的硫酯化，没有观察到可检测到的外消旋化，这使其可用于合成肽硫酯，这是天然化学连接的关键成分。值得一提的是，-OH和吲哚-NH等氨基酸侧链官能团与反应条件相容，无需对其进行保护。此外，这种方法也适用于硒代酯。

  DOI：

  10.1021/acs.joc.1c01949

文献信息

• “BOP” as a reagent for mild and efficient preparation of esters
  作者：Moon H. Kim、Dinesh V. Patel

  DOI：10.1016/s0040-4039(00)77257-1

  日期：1994.8

  A simple procedure for preparation of esters under mild conditions employing the BOP reagent is reported. Acid and base labile protecting groups commonly used with amino acids e.g. t-butyl, Fmoc etc., are well tolerated under these conditions. The mechanism and scope of this reaction are briefly discussed.

  报道了一种使用BOP试剂在温和条件下制备酯的简单方法。在这些条件下，对氨基酸通常使用的酸和碱不稳定的保护基（例如叔丁基，Fmoc等）具有很好的耐受性。简要讨论了该反应的机理和范围。
• Design and synthesis of irreversible inhibitors of foot-and-mouth disease virus 3C protease
  作者：Núria R. Roqué Rosell、Ladan Mokhlesi、Nicholas E. Milton、Trevor R. Sweeney、Patricia A. Zunszain、Stephen Curry、Robin J. Leatherbarrow

  DOI：10.1016/j.bmcl.2013.12.045

  日期：2014.1

  Foot-and-mouth disease virus (FMDV) causes a highly infectious and economically devastating disease of livestock. The FMDV genome is translated as a single polypeptide precursor that is cleaved into functional proteins predominantly by the highly conserved viral 3C protease, making this enzyme an attractive target for antiviral drugs. A peptide corresponding to an optimal substrate has been modified at the C-terminus, by the addition of a warhead, to produce irreversible inhibitors that react as Michael acceptors with the enzyme active site. Further investigation highlighted key structural determinants for inhibition, with a positively charged P2 being particularly important for potency. (C) 2013 Elsevier Ltd. All rights reserved.