N-(trans-β-styrenesulfonyl)-D-allo-threonine | 406951-18-6

• 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: N-(trans-β-styrenesulfonyl)-D-allo-threonine
• 英文别名: (2R,3R)-3-hydroxy-2-[[(E)-2-phenylethenyl]sulfonylamino]butanoic acid
• CAS: 406951-18-6
• 化学式: C₁₂H₁₅NO₅S
• 分子量: 285.321
• InChiKey: HDSMTPQFYWVIFR-FQZVFUSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(trans-β-styrenesulfonyl)-D-allo-threonine 在 10percent Pd/C 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 2-Phenyl-ethanesulfonic acid ((2R,3R)-2-methyl-4-oxo-oxetan-3-yl)-amide
  参考文献：
  名称：

  Serine and Threonine β-Lactones:  A New Class of Hepatitis A Virus 3C Cysteine Proteinase Inhibitors

  摘要：

  Hepatitis A virus (HAV) 3C enzyme is a cysteine proteinase essential for viral replication and infectivity and represents a target for the development of antiviral drugs. A number of serine and threonine beta-lactones were synthesized and tested against HAV 3C proteinase. The D-N-Cbz-serine beta-lactone 5a displays competitive reversible inhibition with a K-i value of 1.50 x 10(-6) M. Its enantiomer, L-N-Cbz-serine beta-lactone 5b is an irreversible inactivator with 0.70 min(-1), K, = 1.84 x 10(-4) M and k(inact)/K-I = 3800 M-1 min(-1). Mass spectrometry and HMQC NMR studies using C-13-labeled 5b show that inactivation of the enzyme occurs by nucleophilic attack of the cysteine thiol (Cys-172) at the beta-position of the oxetanone ring. Although the N-Cbz-serine beta-lactones 5a and 5b display potent inhibition, other related analogues with an N-Cbz side chain, such as the five-membered ring homoserine gamma-lactones 14a and 14b, the four-membered ring beta-lactam 33, 2-methylene oxetane 34, cyclobutanone 36, and 3-azetidinone 39, fail to give significant inhibition of HAV 3C proteinase, thus demonstrating the importance of the beta-lactone ring for binding.

  DOI：

  10.1021/jo0109016
• 作为产物：
  描述：

  反-β-苯乙烯磺酰氯 在 lithium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 N-(trans-β-styrenesulfonyl)-D-allo-threonine
  参考文献：
  名称：

  Serine and Threonine β-Lactones:  A New Class of Hepatitis A Virus 3C Cysteine Proteinase Inhibitors

  摘要：

  Hepatitis A virus (HAV) 3C enzyme is a cysteine proteinase essential for viral replication and infectivity and represents a target for the development of antiviral drugs. A number of serine and threonine beta-lactones were synthesized and tested against HAV 3C proteinase. The D-N-Cbz-serine beta-lactone 5a displays competitive reversible inhibition with a K-i value of 1.50 x 10(-6) M. Its enantiomer, L-N-Cbz-serine beta-lactone 5b is an irreversible inactivator with 0.70 min(-1), K, = 1.84 x 10(-4) M and k(inact)/K-I = 3800 M-1 min(-1). Mass spectrometry and HMQC NMR studies using C-13-labeled 5b show that inactivation of the enzyme occurs by nucleophilic attack of the cysteine thiol (Cys-172) at the beta-position of the oxetanone ring. Although the N-Cbz-serine beta-lactones 5a and 5b display potent inhibition, other related analogues with an N-Cbz side chain, such as the five-membered ring homoserine gamma-lactones 14a and 14b, the four-membered ring beta-lactam 33, 2-methylene oxetane 34, cyclobutanone 36, and 3-azetidinone 39, fail to give significant inhibition of HAV 3C proteinase, thus demonstrating the importance of the beta-lactone ring for binding.

  DOI：

  10.1021/jo0109016

文献信息

• Serine and Threonine β-Lactones:  A New Class of Hepatitis A Virus 3C Cysteine Proteinase Inhibitors
  作者：Manjinder S. Lall、Yeeman K. Ramtohul、Michael N. G. James、John C. Vederas

  DOI：10.1021/jo0109016

  日期：2002.3.1

  Hepatitis A virus (HAV) 3C enzyme is a cysteine proteinase essential for viral replication and infectivity and represents a target for the development of antiviral drugs. A number of serine and threonine beta-lactones were synthesized and tested against HAV 3C proteinase. The D-N-Cbz-serine beta-lactone 5a displays competitive reversible inhibition with a K-i value of 1.50 x 10(-6) M. Its enantiomer, L-N-Cbz-serine beta-lactone 5b is an irreversible inactivator with 0.70 min(-1), K, = 1.84 x 10(-4) M and k(inact)/K-I = 3800 M-1 min(-1). Mass spectrometry and HMQC NMR studies using C-13-labeled 5b show that inactivation of the enzyme occurs by nucleophilic attack of the cysteine thiol (Cys-172) at the beta-position of the oxetanone ring. Although the N-Cbz-serine beta-lactones 5a and 5b display potent inhibition, other related analogues with an N-Cbz side chain, such as the five-membered ring homoserine gamma-lactones 14a and 14b, the four-membered ring beta-lactam 33, 2-methylene oxetane 34, cyclobutanone 36, and 3-azetidinone 39, fail to give significant inhibition of HAV 3C proteinase, thus demonstrating the importance of the beta-lactone ring for binding.