(R,E)-allyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate | 652976-04-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (R,E)-allyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate
• 英文别名: prop-2-enyl (E)-3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]prop-2-enoate
• CAS: 652976-04-0
• 化学式: C₁₂H₁₉NO₅
• 分子量: 257.287
• InChiKey: XWEHPCPYXSBQRM-PORFMDCZSA-N

物化性质

• 沸点：
  496.5±45.0 °C(Predicted)
• 密度：
  1.168±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  8
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  95.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R,E)-allyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate 在 四氢吡咯 、 四(三苯基膦)钯 作用下， 以 四氢呋喃 为溶剂， 以81%的产率得到CJ-15801
  参考文献：
  名称：

  The Antibiotic CJ-15,801 Is an Antimetabolite that Hijacks and Then Inhibits CoA Biosynthesis

  摘要：

  The natural product CJ-15,801 is an inhibitor of Staphylococcus aureus, but not other bacteria. Its close structural resemblance to pantothenic acid, the vitamin precursor of coenzyme A (CoA), and its Michael acceptor moiety suggest that it irreversibly inhibits an enzyme involved in CoA biosynthesis or utilization. However, its mode of action and the basis for its specificity have not been elucidated to date. We demonstrate that CJ-15,801 is transformed by the uniquely selective S. aureus pantothenate kinase, the first CoA biosynthetic enzyme, into a substrate for the next enzyme, phosphopantothenoylcysteine synthetase, which is inhibited through formation of a tight-binding structural mimic of its native reaction intermediate. These findings reveal CJ-15,801 as a vitamin biosynthetic pathway antimetabolite with a mechanism similar to that of the sulfonamide antibiotics and highlight CoA biosynthesis as a viable antimicrobial drug target.

  DOI：

  10.1016/j.chembiol.2012.03.013
• 作为产物：
  描述：

  prop-2-enyl (E)-3-[[(4R)-2,2,5,5-tetramethyl-1,3-dioxane-4-carbonyl]amino]prop-2-enoate 在 bismuth(III) chloride 作用下， 以 水 、 乙腈 为溶剂， 反应 5.0h， 以75%的产率得到(R,E)-allyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate
  参考文献：
  名称：

  The Antibiotic CJ-15,801 Is an Antimetabolite that Hijacks and Then Inhibits CoA Biosynthesis

  摘要：

  The natural product CJ-15,801 is an inhibitor of Staphylococcus aureus, but not other bacteria. Its close structural resemblance to pantothenic acid, the vitamin precursor of coenzyme A (CoA), and its Michael acceptor moiety suggest that it irreversibly inhibits an enzyme involved in CoA biosynthesis or utilization. However, its mode of action and the basis for its specificity have not been elucidated to date. We demonstrate that CJ-15,801 is transformed by the uniquely selective S. aureus pantothenate kinase, the first CoA biosynthetic enzyme, into a substrate for the next enzyme, phosphopantothenoylcysteine synthetase, which is inhibited through formation of a tight-binding structural mimic of its native reaction intermediate. These findings reveal CJ-15,801 as a vitamin biosynthetic pathway antimetabolite with a mechanism similar to that of the sulfonamide antibiotics and highlight CoA biosynthesis as a viable antimicrobial drug target.

  DOI：

  10.1016/j.chembiol.2012.03.013

文献信息

• Copper-Mediated Synthesis of <i>N</i>-Acyl Vinylogous Carbamic Acids and Derivatives:  Synthesis of the Antibiotic CJ-15,801
  作者：Chong Han、Ruichao Shen、Shun Su、John A. Porco

  DOI：10.1021/ol0360041

  日期：2004.1.1

  Copper(I)-mediated C-N bond formation has been employed to prepare both N-acyl vinylogous carbamic acids and ureas. The novel N-acyl vinylogous carbamic acid antibiotic, CJ-15,801, was synthesized using this methodology.
• [EN] A. PROCESS FOR THE PREPARATION OF AMINOACRYLIC ACID DERIVATIVES<br/>[FR] PROCÉDÉ POUR LA PRÉPARATION DE DÉRIVÉS D'ACIDE AMINOACRYLIQUE
  申请人：COUNCIL OF SCIENT & IND RES AN INDIAN REGISTERED BODY INC UNDER THE REGISTRATION OF SOCIETIES ACT AC

  公开号：WO2013054366A8

  公开（公告）日：2013-05-30
• US9193674B2
  申请人：——

  公开号：US9193674B2

  公开（公告）日：2015-11-24
• The Antibiotic CJ-15,801 Is an Antimetabolite that Hijacks and Then Inhibits CoA Biosynthesis
  作者：Renier van der Westhuyzen、Justin C. Hammons、Jordan L. Meier、Samira Dahesh、Wessel J.A. Moolman、Stephen C. Pelly、Victor Nizet、Michael D. Burkart、Erick Strauss

  DOI：10.1016/j.chembiol.2012.03.013

  日期：2012.5

  The natural product CJ-15,801 is an inhibitor of Staphylococcus aureus, but not other bacteria. Its close structural resemblance to pantothenic acid, the vitamin precursor of coenzyme A (CoA), and its Michael acceptor moiety suggest that it irreversibly inhibits an enzyme involved in CoA biosynthesis or utilization. However, its mode of action and the basis for its specificity have not been elucidated to date. We demonstrate that CJ-15,801 is transformed by the uniquely selective S. aureus pantothenate kinase, the first CoA biosynthetic enzyme, into a substrate for the next enzyme, phosphopantothenoylcysteine synthetase, which is inhibited through formation of a tight-binding structural mimic of its native reaction intermediate. These findings reveal CJ-15,801 as a vitamin biosynthetic pathway antimetabolite with a mechanism similar to that of the sulfonamide antibiotics and highlight CoA biosynthesis as a viable antimicrobial drug target.