methyl (2S,3R)-3-(N-tert-butoxycarbonylamino)-2-methyl-5-phenylpentanoate | 368448-94-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: methyl (2S,3R)-3-(N-tert-butoxycarbonylamino)-2-methyl-5-phenylpentanoate
• 英文别名: methyl (2S,3S)-2-methyl-3-[(2-methylpropan-2-yl)oxycarbonylamino]-5-phenylpentanoate
• CAS: 368448-94-6
• 化学式: C₁₈H₂₇NO₄
• 分子量: 321.417
• InChiKey: YMDGENDSLWHIOT-ZFWWWQNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (2S,3R)-3-(N-tert-butoxycarbonylamino)-2-methyl-5-phenylpentanoate 在 lithium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 为溶剂， 反应 6.25h， 生成 (2S,3S,4E)-3-(N-tert-butoxycarbonylamino)-2-methyl-5-phenylpent-4-enoic acid
  参考文献：
  名称：

  Serine–threonine protein phosphatase inhibitors derived from nodularin: role of the 2-methyl and 3-diene groups in the Adda residue and the effect of macrocyclic conformational restraint

  摘要：

  PP1cat酶抑制剂对环状结构的影响

  DOI：

  10.1039/b100402f
• 作为产物：
  描述：

  (2E,4E)-methyl 5-phenylpenta-2,4-dienoate 在 palladium dihydroxide 正丁基锂 、 ammonium formate 、 sodium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 为溶剂， 反应 7.75h， 生成 methyl (2S,3R)-3-(N-tert-butoxycarbonylamino)-2-methyl-5-phenylpentanoate
  参考文献：
  名称：

  Serine–threonine protein phosphatase inhibitors derived from nodularin: role of the 2-methyl and 3-diene groups in the Adda residue and the effect of macrocyclic conformational restraint

  摘要：

  PP1cat酶抑制剂对环状结构的影响

  DOI：

  10.1039/b100402f

文献信息

• Serine–threonine protein phosphatase inhibitors derived from nodularin: role of the 2-methyl and 3-diene groups in the Adda residue and the effect of macrocyclic conformational restraint
  作者：Michael E. O'Donnell、Jonathan Sanvoisin、David Gani

  DOI：10.1039/b100402f

  日期：——

  In order to probe the effect upon macrocycle conformation and PP1cat enzyme inhibition of structural changes to nodularin, specific replacements for the Adda residue were introduced. Two new analogues, cyclo[-(3S,E)-3-phenylethenyl-3-aminopropanoyl-α-(R)-Glu-α-OH-γ-Sar-(R)-Asp-α-OH-β-(S)-Phe-] 19a and cyclo[-(2S,3S,E)-2-methyl-3-phenylethenyl-3-aminopropanoyl-β-(R)-Glu-α-OH-γ-Sar-(R)-Asp-α-OH-β-(S)-Phe-] 19b were prepared incorporating previously optimised preparative protocols [see previous article, K. L. Webster, A. B. Maude, M. E. O'Donnell, A. P. Mehrotra and D. Gani, J. Chem. Soc., Perkin Trans. 1 (DOI: 10.1039/b100401h)], and these differed only at C-2 of the Adda residue. The presence of a (2S)-methyl group in compound 19b stabilised the trans-rotameric form of the (2R)-Glu-γ-Sar amide bond in solution as determined by NMR spectroscopic analysis (trans–cis; 10:1), and enhanced efficacy as a PP1cat inhibitor by 20-fold over compound 19a. The methyl homologue displayed a competitive mode of inhibition, with respect to the substrate Ac-Arg-Arg-Thr(P)-Val-Ala and displayed a Ki value of 206 ± 30 μmol dm−3. Substitution of the Sar residue in the methyl homologue by (2S)-Pro gave a competitive inhibitor of similar efficacy (Ki = 400 ± 75 μmol dm−3). The proline analogue 22 existed as a 6:1 mixture of trans–cis rotamers. Evidently the trans-rotamer of the (2S)-Pro-containing compound differed in conformational structure compared to the sarcosine-containing variant, only close to the site of the substitution. A structural model for the inhibition of PP1cat and a strategy for the selective inhibition of PP1 over PP2A are discussed within the context of the results.

  PP1cat酶抑制剂对环状结构的影响