(R,E)-methyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate | 1265205-82-0

• 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)-methyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate
• 英文别名: CJ-OMe；methyl (E)-3-[[(2R)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]prop-2-enoate
• CAS: 1265205-82-0
• 化学式: C₁₀H₁₇NO₅
• 分子量: 231.249
• InChiKey: UBHGRZXGLNTOPY-ZJELKQJVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 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)-methyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate 在 盐酸 、 magnesium chloride 作用下， 以 水 为溶剂， 以98%的产率得到P-CJ-OMe
  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：

  D-(-)-泛酰内酯 在 bismuth(III) chloride 、 正丁基锂 、 氨 、 4-甲基苯磺酸吡啶 作用下， 以 四氢呋喃 、 正己烷 、 水 、 乙腈 、 苯 为溶剂， 反应 22.08h， 生成 (R,E)-methyl 3-(2,4-dihydroxy-3,3-dimethylbutanamido)acrylate
  参考文献：
  名称：

  Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801

  摘要：

  The fast and efficient syntheses of pantothenic acid and the antiparasitic agent CJ-15,801 have been achieved starting from a common imide unit through the selective manipulation of enamide intermediates.

  DOI：

  10.1021/ol103114w

文献信息

• Structure-activity analysis of CJ-15,801 analogues that interact with Plasmodium falciparum pantothenate kinase and inhibit parasite proliferation
  作者：Christina Spry、Alan L. Sewell、Yuliya Hering、Mathew V.J. Villa、Jonas Weber、Stephen J. Hobson、Suzannah J. Harnor、Sheraz Gul、Rodolfo Marquez、Kevin J. Saliba

  DOI：10.1016/j.ejmech.2017.08.050

  日期：2018.1

  and the trans-substituted double bond of CJ-15,801 is important for the selective, on-target antiplasmodial effect, while replacement of the carboxyl group is permitted, and, in one case, favored. Additionally, we show that the antiplasmodial potency of CJ-15,801 analogues that retain the R-pantoyl and trans-substituted enamide moieties correlates with inhibition of P. falciparum pantothenate kinase

  人类疟疾寄生虫恶性疟原虫的存活取决于泛酸（维生素B 5），泛酸是基本酶辅因子辅酶A的前体。CJ-15,801，泛酸的酰胺类似物，从真菌Seimatosporium sp。分离。先前显示，CL28611可通过靶向泛酸利用来抑制恶性疟原虫的体外增殖。为了告知下一代类似物的设计，我们着手合成和测试了一系列合成的带有酰胺基的泛酸类似物。我们证明了R-泛酰基部分和反式的守恒CJ-15,801的双取代双键对于选择性的靶向抗血浆药物作用很重要，同时允许羧基取代，在一种情况下，这是有利的。此外，我们显示保留R-泛酰基和反式取代的酰胺基部分的CJ-15,801类似物的抗血浆活性与抑制恶性疟原虫泛酸激酶（Pf PanK）催化的泛酸磷酸化相关，暗示与Pf PanK的相互作用为抗疟原虫活性的关键决定因素。
• Fast and Flexible Synthesis of Pantothenic Acid and CJ-15,801
  作者：Alan L. Sewell、Mathew V. J. Villa、Mhairi Matheson、William G. Whittingham、Rodolfo Marquez

  DOI：10.1021/ol103114w

  日期：2011.2.18

  The fast and efficient syntheses of pantothenic acid and the antiparasitic agent CJ-15,801 have been achieved starting from a common imide unit through the selective manipulation of enamide intermediates.
• 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.