2-[(Adamantan-1-yloxy)-aminomethyl-phosphinoylmethyl]-4-methyl-pentanoic acid | 305820-23-9

• 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: 2-[(Adamantan-1-yloxy)-aminomethyl-phosphinoylmethyl]-4-methyl-pentanoic acid
• CAS: 305820-23-9
• 化学式: C₁₈H₃₂NO₄P
• 分子量: 357.43
• InChiKey: FSNFRINFYUQNLE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.91
• 重原子数：
  24.0
• 可旋转键数：
  8.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  89.62
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  9-芴甲基-N-琥珀酰亚胺基碳酸酯 、 2-[(Adamantan-1-yloxy)-aminomethyl-phosphinoylmethyl]-4-methyl-pentanoic acid 在 碳酸氢钠 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 以65%的产率得到O-Adamantyl P-(9-fluorenylmethyloxycarbonylaminoethyl)-P-(2-isobutylpropionic acid-3-yl)phosphinate
  参考文献：
  名称：

  Phosphinic Peptide Matrix Metalloproteinase-9 Inhibitors by Solid-Phase Synthesis Using a Building Block Approach

  摘要：

  The solid-phase synthesis of an array of different pseudopeptides containing a phosphinic glycine-leucine moiety (-G Psi/{P(O)OH-CH2}L-)([1]) is described. The resulting pseudopeptides were shown to act as matrix metalloproteinase-9 (MMP-9) inhibitors. Starting from available materials, the protected amino acid isosters benzyloxy-carbonyl aminomethylphosphinic acid (glycine analogue) and ethyl alpha-isobutylacrylate (leucine analogue) were synthesized and coupled with the bis(trimethylsilyl)phosphonite. Protective group interchange yielded a protected phosphinic dipeptide building block 1 ready for use in solid-phase peptide synthesis, Solid-phase peptide synthesis was performed with 9-fluorenylmethyloxycarbonyl (Fmoc) chemistry on a polyethylene glycol polyamide (PEGA) support and the coupling of 1 (1.5 equiv) was carried out with standard activation. The P-4-P-2 and P-2'-P-4' positions of the pseudopeptides were designed by analogy of the cleavage sequences of different natural extracellular matrix protein substrates with a synthetic peptide substrate of MMP-9. The crude peptides were obtained in high yield and purity as determined by RP-HPLC, and were characterized by electrospray mass spectrometry and amino acid analysis after purification. Enzyme kinetic investigations with MMP-9 of the purified peptide inhibitors showed Ki values in the range from mM to nM.

  DOI：

  10.1002/(sici)1521-3765(19991001)5:10<2877::aid-chem2877>3.0.co;2-z
• 作为产物：
  描述：

  1-溴金刚烷 在 palladium on activated charcoal sodium hydroxide 、 水 、 氢气 、 silver(l) oxide 作用下， 以 甲醇 、 乙醇 、 氯仿 、 乙酸乙酯 为溶剂， 反应 24.0h， 生成 2-[(Adamantan-1-yloxy)-aminomethyl-phosphinoylmethyl]-4-methyl-pentanoic acid
  参考文献：
  名称：

  Phosphinic Peptide Matrix Metalloproteinase-9 Inhibitors by Solid-Phase Synthesis Using a Building Block Approach

  摘要：

  The solid-phase synthesis of an array of different pseudopeptides containing a phosphinic glycine-leucine moiety (-G Psi/{P(O)OH-CH2}L-)([1]) is described. The resulting pseudopeptides were shown to act as matrix metalloproteinase-9 (MMP-9) inhibitors. Starting from available materials, the protected amino acid isosters benzyloxy-carbonyl aminomethylphosphinic acid (glycine analogue) and ethyl alpha-isobutylacrylate (leucine analogue) were synthesized and coupled with the bis(trimethylsilyl)phosphonite. Protective group interchange yielded a protected phosphinic dipeptide building block 1 ready for use in solid-phase peptide synthesis, Solid-phase peptide synthesis was performed with 9-fluorenylmethyloxycarbonyl (Fmoc) chemistry on a polyethylene glycol polyamide (PEGA) support and the coupling of 1 (1.5 equiv) was carried out with standard activation. The P-4-P-2 and P-2'-P-4' positions of the pseudopeptides were designed by analogy of the cleavage sequences of different natural extracellular matrix protein substrates with a synthetic peptide substrate of MMP-9. The crude peptides were obtained in high yield and purity as determined by RP-HPLC, and were characterized by electrospray mass spectrometry and amino acid analysis after purification. Enzyme kinetic investigations with MMP-9 of the purified peptide inhibitors showed Ki values in the range from mM to nM.

  DOI：

  10.1002/(sici)1521-3765(19991001)5:10<2877::aid-chem2877>3.0.co;2-z