S-(dimethylamino)methyl ethanethioate | 1696-27-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 硫代羧酸及其衍生物
• 英文名称: S-(dimethylamino)methyl ethanethioate
• 英文别名: Dimethylamino-methanthiol-acetat；S-[(dimethylamino)methyl] ethanethioate
• CAS: 1696-27-1
• 化学式: C₅H₁₁NOS
• 分子量: 133.214
• InChiKey: DIWHMBSCKLBLEL-UHFFFAOYSA-N

物化性质

• 沸点：
  146.4±23.0 °C(Predicted)
• 密度：
  1.029±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  45.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  S-(dimethylamino)methyl ethanethioate 、 苄胺 以 1,4-二氧六环 、 水 为溶剂， 生成 N-苄基乙酰胺
  参考文献：
  名称：

  氨基甲基硫代酸酯在天然化学连接型酰胺键形成反应中是否可行？

  摘要：

  N-巯基甲基胺和硫酯的缩合是通过氨基甲基硫酯中间体在天然化学连接类型方法中随后自裂解“巯基甲基”助剂的酰胺的潜在途径。本文介绍了对氨基甲基硫代酯的制备以及随后由甲醛，硫代酸和胺的三组分偶合转化为酰胺的研究。我们的研究表明，尽管此类中间体可能在酰胺生成过程中形成，但与胺和硫代酸前体的直接反应相比，没有优势。

  DOI：

  10.1071/ch18198
• 作为产物：
  描述：

  N,N-二甲基氯烯亚胺 、 potassium thioacetate 以 乙醚 为溶剂， 以88%的产率得到S-(dimethylamino)methyl ethanethioate
  参考文献：
  名称：

  Hydrolysis of low concentrations of the acetylthiocholine analogs acetyl(homo)thiocholine and acetyl(nor)thiocholine by acetylcholinesterase may be limited by selective gating at the enzyme peripheral site

  摘要：

  Hydrolysis of acetylcholine by acetylcholinesterase (AChE) is extremely rapid, with a second-order hydrolysis rate constant k(E) (often denoted k(cat)/K-m) that approaches 10(8) M-1 s(-1). AChE contains a deep active site gorge with two sites,of ligand binding, an acylation site (or A-site) containing the catalytic triad at the base of the gorge and a peripheral site (or P-site) near the gorge entrance. The P-site is known to contribute to catalytic efficiency with acetylthiocholine (AcSCh) by transiently trapping the substrate in a low affinity complex on its way to the A-site, where a short-lived acyl enzyme intermediate is produced. Here we ask whether the P-site does more than simply trap the substrate but in fact selectively gates entry to the A-site to provide specificity for AcSCh (and acetylcholine) relative to the close structural analogs acetyl(homo)thiocholine (Ac-hSCh, which adds one additional methylene group to thiocholine) and acetyl(nor)thiocholine (Ac-nSCh, which deletes one methylene group from thiocholine). We synthesized Ac-hSCh and Ac-nSCh and overcame technical difficulties associated with instability of the northiocholine hydrolysis product. We then compared the catalytic parameters of these substrates with AChE to those of AcSCh. Values of k(E) for Ac-hSCh and Ac-nSCh were about 2% of that for AcSCh. The k(E) for AcSCh is close to the theoretical diffusion-controlled limit for the substrate association rate constant, but k(E) values for Ac-hSCh or Ac-nSCh are too low to be limited by diffusion control. However, analyses of kinetic solvent isotope effects and inhibition patterns for P-site inhibitors indicate that these two analogs also do not equilibrate with the A-site prior to the initial acylation step of catalysis. We propose that k(E) for these substrates is partially rate-limited by a gating step that involves the movement of bound substrate from the P-site to the A-site. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.cbi.2012.09.017

文献信息

• Synthesis and Properties of α-Aminothiol Esters^1,2
  作者：Scott Searles、Shogo Nukina、Eugene R. Magnuson

  DOI：10.1021/jo01017a050

  日期：1965.6
• Are Aminomethyl Thioesters Viable Intermediates in Native Chemical Ligation Type Amide Bond Forming Reactions?
  作者：Carlie L. Charron、Jade M. Cottam Jones、Craig A. Hutton

  DOI：10.1071/ch18198

  日期：——

  The condensation of N-mercaptomethyl amines and thioesters is a potential route to amides, via aminomethyl thioester intermediates, in a native chemical ligation type process followed by self-cleavage of the ‘mercaptomethyl’ auxiliary. This paper describes investigations towards the preparation of aminomethyl thioesters, and subsequent conversion into amides, from a three-component coupling of formaldehyde

  N-巯基甲基胺和硫酯的缩合是通过氨基甲基硫酯中间体在天然化学连接类型方法中随后自裂解“巯基甲基”助剂的酰胺的潜在途径。本文介绍了对氨基甲基硫代酯的制备以及随后由甲醛，硫代酸和胺的三组分偶合转化为酰胺的研究。我们的研究表明，尽管此类中间体可能在酰胺生成过程中形成，但与胺和硫代酸前体的直接反应相比，没有优势。
• Hydrolysis of low concentrations of the acetylthiocholine analogs acetyl(homo)thiocholine and acetyl(nor)thiocholine by acetylcholinesterase may be limited by selective gating at the enzyme peripheral site
  作者：Veena Beri、Jeffrey T. Auletta、Ghulam M. Maharvi、Juanita F. Wood、Abdul H. Fauq、Terrone L. Rosenberry

  DOI：10.1016/j.cbi.2012.09.017

  日期：2013.3

  Hydrolysis of acetylcholine by acetylcholinesterase (AChE) is extremely rapid, with a second-order hydrolysis rate constant k(E) (often denoted k(cat)/K-m) that approaches 10(8) M-1 s(-1). AChE contains a deep active site gorge with two sites,of ligand binding, an acylation site (or A-site) containing the catalytic triad at the base of the gorge and a peripheral site (or P-site) near the gorge entrance. The P-site is known to contribute to catalytic efficiency with acetylthiocholine (AcSCh) by transiently trapping the substrate in a low affinity complex on its way to the A-site, where a short-lived acyl enzyme intermediate is produced. Here we ask whether the P-site does more than simply trap the substrate but in fact selectively gates entry to the A-site to provide specificity for AcSCh (and acetylcholine) relative to the close structural analogs acetyl(homo)thiocholine (Ac-hSCh, which adds one additional methylene group to thiocholine) and acetyl(nor)thiocholine (Ac-nSCh, which deletes one methylene group from thiocholine). We synthesized Ac-hSCh and Ac-nSCh and overcame technical difficulties associated with instability of the northiocholine hydrolysis product. We then compared the catalytic parameters of these substrates with AChE to those of AcSCh. Values of k(E) for Ac-hSCh and Ac-nSCh were about 2% of that for AcSCh. The k(E) for AcSCh is close to the theoretical diffusion-controlled limit for the substrate association rate constant, but k(E) values for Ac-hSCh or Ac-nSCh are too low to be limited by diffusion control. However, analyses of kinetic solvent isotope effects and inhibition patterns for P-site inhibitors indicate that these two analogs also do not equilibrate with the A-site prior to the initial acylation step of catalysis. We propose that k(E) for these substrates is partially rate-limited by a gating step that involves the movement of bound substrate from the P-site to the A-site. (C) 2012 Elsevier Ireland Ltd. All rights reserved.