(+/-)-p-nitrophenyl N-(benzyloxycarbonyl)-α-aminododecanoic acid | 66398-13-8

• 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: (+/-)-p-nitrophenyl N-(benzyloxycarbonyl)-α-aminododecanoic acid
• 英文别名: (4-nitrophenyl) 2-(phenylmethoxycarbonylamino)dodecanoate
• CAS: 66398-13-8
• 化学式: C₂₆H₃₄N₂O₆
• 分子量: 470.566
• InChiKey: SZFDMAQOGRBRKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.33
• 重原子数：
  34.0
• 可旋转键数：
  15.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  107.77
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (+/-)-p-nitrophenyl N-(benzyloxycarbonyl)-α-aminododecanoic acid 在 钯 N-甲基吗啉 、 氢气 、 1-羟基苯并三唑 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 (2-Amino-dodecanoylamino)-[(2R,3S,4R,5R)-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-3,4-dihydroxy-tetrahydro-furan-2-yl]-acetic acid; compound with formic acid
  参考文献：
  名称：

  Synthesis and anticandidal properties of polyoxin L analogs containing .alpha.-amino fatty acids

  摘要：

  Analogues of polyoxin L containing amino acids with saturated fatty acid like side chains were synthesized from the benzyloxycarbonyl-protected alpha-amino fatty acid p-nitrophenyl ester and uracil polyoxin C. Transfer hydrogenolysis using palladium black and formic acid gave diastereomeric, dipeptidyl polyoxin L analogues containing alpha-aminooctanoic acid (3), alpha-aminododecanoic acid (4), or alpha-aminohexadecanoic acid (5) as the amine terminal residue in 40-60% yield. Diastereomers of 3 and 5 were resolved by using high-performance liquid chromatography on a reversed-phase column and designated as 3a, 3b and 5a, 5b. Analogues 3-5 were excellent inhibitors of chitin synthetase from Candida albicans; 4, the best inhibitor, had an ID50 of 0.5 microM. The L,L diastereomers of 3 and 5 were 1-2 orders of magnitude more potent chitin synthetase inhibitors than their D,L homologues. None of the synthetic polyoxin L analogues inhibited transport of trimethionine, but 3a, 4, and 5b caused decreases of 71%, 87%, and 83%, respectively, in the initial rate of uptake of dileucine. Compounds 3-5 were significantly more stable to peptidase degradation than polyoxin L analogues containing naturally occurring alpha-amino acids. Compound 4 inhibited growth of C. albicans in culture at 40-80 micrograms/mL. All other analogues were less potent antifungals. The results suggest that synthetic polyoxins can be designed to have increased affinity for a peptide transport system and to have increased stability against intracellular degradation in C. albicans.

  DOI：

  10.1021/jm00398a027
• 作为产物：
  描述：

  (+/-)-2-氨基十二酸 在 sodium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 47.0h， 生成 (+/-)-p-nitrophenyl N-(benzyloxycarbonyl)-α-aminododecanoic acid
  参考文献：
  名称：

  Synthesis and anticandidal properties of polyoxin L analogs containing .alpha.-amino fatty acids

  摘要：

  Analogues of polyoxin L containing amino acids with saturated fatty acid like side chains were synthesized from the benzyloxycarbonyl-protected alpha-amino fatty acid p-nitrophenyl ester and uracil polyoxin C. Transfer hydrogenolysis using palladium black and formic acid gave diastereomeric, dipeptidyl polyoxin L analogues containing alpha-aminooctanoic acid (3), alpha-aminododecanoic acid (4), or alpha-aminohexadecanoic acid (5) as the amine terminal residue in 40-60% yield. Diastereomers of 3 and 5 were resolved by using high-performance liquid chromatography on a reversed-phase column and designated as 3a, 3b and 5a, 5b. Analogues 3-5 were excellent inhibitors of chitin synthetase from Candida albicans; 4, the best inhibitor, had an ID50 of 0.5 microM. The L,L diastereomers of 3 and 5 were 1-2 orders of magnitude more potent chitin synthetase inhibitors than their D,L homologues. None of the synthetic polyoxin L analogues inhibited transport of trimethionine, but 3a, 4, and 5b caused decreases of 71%, 87%, and 83%, respectively, in the initial rate of uptake of dileucine. Compounds 3-5 were significantly more stable to peptidase degradation than polyoxin L analogues containing naturally occurring alpha-amino acids. Compound 4 inhibited growth of C. albicans in culture at 40-80 micrograms/mL. All other analogues were less potent antifungals. The results suggest that synthetic polyoxins can be designed to have increased affinity for a peptide transport system and to have increased stability against intracellular degradation in C. albicans.

  DOI：

  10.1021/jm00398a027

文献信息

• KHARE, R. K.;BECKER, JEFFREY M.;NAIDER, FRED R., J. MED. CHEM., 31,(1988) N 3, 650-656
  作者：KHARE, R. K.、BECKER, JEFFREY M.、NAIDER, FRED R.

  DOI：——

  日期：——