(R)-2-Acetylamino-3-(2-methoxycarbonyl-ethylsulfanyl)-propionic acid methyl ester | 85680-04-2

• 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: (R)-2-Acetylamino-3-(2-methoxycarbonyl-ethylsulfanyl)-propionic acid methyl ester
• 英文别名: methyl (2R)-2-acetamido-3-(2-methoxycarbonylethylsulfanyl)propanoate；methyl (2R)-2-acetamido-3-(3-methoxy-3-oxopropyl)sulfanylpropanoate
• CAS: 85680-04-2
• 化学式: C₁₀H₁₇NO₅S
• 分子量: 263.315
• InChiKey: UUWIGRAKKYJSQT-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  17
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N-乙酰基-L-半胱氨酸甲酯 、 丙烯酸甲酯（MA） 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 生成 (R)-2-Acetylamino-3-(2-methoxycarbonyl-ethylsulfanyl)-propionic acid methyl ester
  参考文献：
  名称：

  使用乙烯基磺酰胺作为硫醇-迈克尔“点击”受体的肽在树脂上的宏环化

  摘要：

  线性肽的大环化赋予酶促降解改善的稳定性，并增加了功能的效力。已经在溶液和在树脂上成功实现了许多肽的大环化，但是由于它们缺乏选择性，需要较长的反应时间或需要加热，因此其范围受到限制。为了克服这些缺点，开发了一种鲁棒而又简便的策略，该方法采用硫醇-迈克尔点击化学，通过N-甲基乙烯基磺酰胺。我们通过FTIR模型动力学研究证明其反应性和高稳定性之间的平衡，在30分钟内达到88％的转化率，以及NMR稳定性研究，表明在碱性条件下在8天的时间内没有明显的降解。使用可商购的试剂2-氯乙烷磺酰氯，将细胞粘附肽RGDS官能化并在树脂上大环化，相对效率超过95％。该方法的简单性质证明了乙烯基磺酰胺作为硫醇-迈克尔点击受体的有效性及其在许多其他生物缀合应用中的适用性。

  DOI：

  10.1021/acs.bioconjchem.8b00751

文献信息

• Identification of Novel Metabolites of Butadiene Monoepoxide in Rats and Mice
  作者：Kevan A. Richardson、Melanie M. C. G. Peters、René H. J. J. J. Megens、Paul A. van Elburg、Bernard T. Golding、Peter J. Boogaard、William P. Watson、Nico J. van Sittert

  DOI：10.1021/tx970175v

  日期：1998.12.1

  Differences in the metabolism of 1,3-butadiene (Bd) in rats and mice may account for the observed species difference in carcinogenicity. Previous studies of the metabolic fate of Ed have identified epoxide formation as a key metabolic transformation which gives 1,2-epoxy-3-butene (BMO), although some evidence of aldehyde metabolites is reported. In this study, male Sprague-Dawley rats and male B6C3F1 mice received single doses of [4-C-14]BMO at 1, 5, 20, and 50 mg/kg of body weight (0.014, 0.071, 0.286, and 0.714 mmol/kg of body weight). Analysis of urinary metabolites indicated that both species preferentially metabolize BMO by direct reaction with GSH when given by ip administration. The excretion of (R)-2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene (IIa), 1-(N-acetyl-L-cystein-S-yl)-2-(S)-hydroxybut-3-ene (IIb), 1-(N-acetyl-L-cystein-S-yl)-2-(R)-hydroxybut-3-ene (IIc), and (S)-2-(N-acetyl-L-cystein-S-yl)- 1-hydroxybut-3-ene (IId) accounted for 48-64% of urinary radioactivity in rats and 46-54% in mice. The metabolites originating from the R-stereoisomer of BMO (IIc and IId) predominated over those arising from the S-stereoisomer (IIa and IIb) in both species. IIc was formed preferentially in mice and IId in rats. The corresponding mercaptoacetic acids, S-(1-hydroxybut-3-en-2-yl)mercaptoacetic acid (IIf) and S-(2-hydroxybut-3-en-1-yl)mercaptoacetic acid (IIg), were identified only in mouse urine (ca. 20% of the recovered radioactivity,, 4-(N-Acetyl-L-cystein-S-yl)- 1,2-dihydroxybutane (Ia), a metabolite derived from hydrolysis of BMO, accounted for 10-17% of the radioactivity in rat and 6-10% in mouse urine. 4-(N-Acetyl-L-cystein-S-yl)-2-hydroxybutanoic acid (1b), 3-(N-acetyl-L-cystein-S-yl)propan-1-ol (Ic), and 3-(N-acetyl-L-cystein-S-yl)propanoic acid (Id:). also derived from the hydrolysis of RR IO, were only present in the rat. Metabolites of 1,2,3,4-diepoxybutane (DEB) were not detected after administration of BMO in rat or mouse urine. This study showed both quantitative and qualitative differences in the metabolism of BMO with varying doses and between species. The data aid in the safety evaluation of Ed and contribute to the interpretation of mathematical models developed for quantitative risk assessment and extrapolation of animals to humans.
• On-Resin Macrocyclization of Peptides Using Vinyl Sulfonamides as a Thiol-Michael “Click” Acceptor
  作者：Bryan P. Sutherland、Bassil M. El-Zaatari、Nicole I. Halaszynski、Jonathan M. French、Shi Bai、Christopher J. Kloxin

  DOI：10.1021/acs.bioconjchem.8b00751

  日期：2018.12.19

  Macrocyclization of linear peptides imparts improved stability to enzymatic degradation and increases potency of function. Many successful macrocyclization of peptides both in solution and on-resin have been achieved but are limited in scope as they lack selectivity, require long reaction times, or necessitate heat. To overcome these drawbacks a robust and facile strategy was developed employing thiol-Michael

  线性肽的大环化赋予酶促降解改善的稳定性，并增加了功能的效力。已经在溶液和在树脂上成功实现了许多肽的大环化，但是由于它们缺乏选择性，需要较长的反应时间或需要加热，因此其范围受到限制。为了克服这些缺点，开发了一种鲁棒而又简便的策略，该方法采用硫醇-迈克尔点击化学，通过N-甲基乙烯基磺酰胺。我们通过FTIR模型动力学研究证明其反应性和高稳定性之间的平衡，在30分钟内达到88％的转化率，以及NMR稳定性研究，表明在碱性条件下在8天的时间内没有明显的降解。使用可商购的试剂2-氯乙烷磺酰氯，将细胞粘附肽RGDS官能化并在树脂上大环化，相对效率超过95％。该方法的简单性质证明了乙烯基磺酰胺作为硫醇-迈克尔点击受体的有效性及其在许多其他生物缀合应用中的适用性。