(S)-methyl 6-acetamido-2-(benzyloxycarbonylamino)hexanoate | 135837-38-6

• 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)-methyl 6-acetamido-2-(benzyloxycarbonylamino)hexanoate
• 英文别名: methyl (2S)-6-acetamido-2-(phenylmethoxycarbonylamino)hexanoate
• CAS: 135837-38-6
• 化学式: C₁₇H₂₄N₂O₅
• 分子量: 336.388
• InChiKey: AKZNEMLEURBPPN-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.76
• 重原子数：
  24.0
• 可旋转键数：
  9.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  93.73
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (S)-methyl 6-acetamido-2-(benzyloxycarbonylamino)hexanoate 在 Woollins 试剂 作用下， 以 甲苯 为溶剂， 以23%的产率得到(S)-methyl 2-(benzyloxycarbonylamino)-6-ethaneselenoamidohexanoate
  参考文献：
  名称：

  Nε-Modified lysine containing inhibitors for SIRT1 and SIRT2

  摘要：

  Sirtuins catalyze the NAD(+) dependent deacetylation of N-epsilon-acetyl lysine residues to nicotinamide, O '-acetyl- ADP-ribose (OAADPR) and N-epsilon-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel N-epsilon-modified lysine containing inhibitors against SIRT1 and SIRT2. N-epsilon-Selenoacetyl and N-epsilon-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied N-epsilon-thioacetyl group. The N-epsilon-3,3-dimethylacryl and N-epsilon-isovaleryl moieties gave significant inhibition in comparison to the N-epsilon-acetyl group present in the substrates. In addition, the studied N-epsilon-alkanoyl, N-epsilon-alpha,beta-unsaturated carbonyl and N-epsilon-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the N-epsilon-modification. These results are applicable for further screening of Ne-acetyl analogues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.035
• 作为产物：
  描述：

  乙酸酐 、 N-(benzyloxycarbonyl)lysine methyl ester hydrochloride 在 吡啶 作用下， 以1.7 g的产率得到(S)-methyl 6-acetamido-2-(benzyloxycarbonylamino)hexanoate
  参考文献：
  名称：

  Nε-Modified lysine containing inhibitors for SIRT1 and SIRT2

  摘要：

  Sirtuins catalyze the NAD(+) dependent deacetylation of N-epsilon-acetyl lysine residues to nicotinamide, O '-acetyl- ADP-ribose (OAADPR) and N-epsilon-deacetylated lysine. Here, an easy-to-synthesize Ac-Ala-Lys-Ala sequence has been used as a probe for the screening of novel N-epsilon-modified lysine containing inhibitors against SIRT1 and SIRT2. N-epsilon-Selenoacetyl and N-epsilon-isothiovaleryl were the most potent moieties found in this study, comparable to the widely studied N-epsilon-thioacetyl group. The N-epsilon-3,3-dimethylacryl and N-epsilon-isovaleryl moieties gave significant inhibition in comparison to the N-epsilon-acetyl group present in the substrates. In addition, the studied N-epsilon-alkanoyl, N-epsilon-alpha,beta-unsaturated carbonyl and N-epsilon-aroyl moieties showed that the acetyl binding pocket can accept rather large groups, but is sensitive to even small changes in electronic and steric properties of the N-epsilon-modification. These results are applicable for further screening of Ne-acetyl analogues. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.06.035

文献信息

• Radical acylation of L-lysine derivatives and L-lysine-containing peptides by peroxynitrite-treated diacetyl and methylglyoxal
  作者：R. Tokikawa、C. Loffredo、M. Uemi、M. T. Machini、E. J. H. Bechara

  DOI：10.3109/10715762.2013.871386

  日期：2014.3

  alpha-dicarbonyls such as diacetyl, methylglyoxal, 3-deoxyglucosone, and4,5-dioxovaleric acid have been characterized as secondary catabolites that can aggregate proteins and form DNA nucleobase adducts in several human maladies, including Alzheimer's disease, rheumatoid arthritis, diabetes, sepsis, renal failure, and respiratory distress syndrome. In vitro, diacetyl and methylglyoxal have also been shown to rapidly

  具有高度亲电性的α-二羰基化合物，例如二乙酰基，甲基乙二醛，3-脱氧葡萄糖苷和4,5-二氧戊酸，已被表征为可在多种人类疾病中聚集蛋白质并形成DNA核碱基加合物的次级分解代谢产物，包括阿尔茨海默氏病，类风湿性关节炎，败血症，肾衰竭和呼吸窘迫综合征。在体外，二乙酰基和甲基乙二醛也已显示出迅速添加过氧亚硝酸盐阴离子（k2〜10（4）-10（5）M（-1）s（-1）），有效的生物亲核试剂，氧化剂和亚硝化剂然后通过可修饰氨基酸的乙酰基中间体将碳链裂解为羧酸。在这项研究中，我们使用了氨基酸衍生物Ac-Lys-OMe和Z-Lys-OMe合成了四肽H-KALA-OH，Ac-KALA-OH，和HK（Boc）ALA-OH揭示由α-二羰基/过亚硝酸盐系统生成的酰基靶向的优先Lys氨基。反应的pH值呈钟形，峰值约为7.5。因此，它们接近ONOOH和催化性H2PO4（-）阴离子的pKa值。反应产物的RP-HPLC和