5-Decyl-4-hydroxy-3,5-dimethyl-thiophen-2-one | 348113-82-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢噻吩类
• 英文名称: 5-Decyl-4-hydroxy-3,5-dimethyl-thiophen-2-one
• 英文别名: 5-decyl-4-hydroxy-3,5-dimethylthiophen-2-one
• CAS: 348113-82-6
• 化学式: C₁₆H₂₈O₂S
• 分子量: 284.463
• InChiKey: DBAHHMIIZICSCD-UHFFFAOYSA-N

物化性质

• 熔点：
  74-75 °C
• 沸点：
  393.5±42.0 °C(Predicted)
• 密度：
  1.019±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  62.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-溴丙烯 、 5-Decyl-4-hydroxy-3,5-dimethyl-thiophen-2-one 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 以61%的产率得到3-Allyl-5-decyl-3,5-dimethyl-thiophene-2,4-dione
  参考文献：
  名称：

  Analogues of Thiolactomycin as Potential Antimalarial Agents

  摘要：

  Analogues of the natural antibiotic thiolactomycin (TLM), an inhibitor of the condensing reactions of type II fatty acid synthase, were synthesized and evaluated for their ability to inhibit the growth of the malaria parasite Plasmodium falciparum. Alkylation of the C4 hydroxyl group led to the most significant increase in growth inhibition (over a 100-fold increase in activity compared to TLM). To investigate the mode of action, the P. falciparum KASIII enzyme was produced for inhibitor assay. A number of TLM derivatives were identified that showed improved inhibition of this enzyme compared to TLM. Structure-activity relationships for enzyme inhibition were identified for some series of TLM analogues, and these also showed weak correlation with inhibition of parasite growth, but this did not hold for other series. On the basis of the lack of a clear correlation between inhibition of pfKASIII activity and parasite growth, we conclude that pfKASIII is not the primary target of TLM analogues. Some of the analogues also inhibited the growth of the parasitic protozoa Trypanosoma cruzi, T. brucei, and Leishmania donovani.

  DOI：

  10.1021/jm049067d
• 作为产物：
  描述：

  4-acetylsulfanyl-2-methyl-3-oxopentanoic acid methyl ester 在 N,N-二甲基丙烯基脲 、 氢氧化钾 、 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 3.5h， 生成 5-Decyl-4-hydroxy-3,5-dimethyl-thiophen-2-one
  参考文献：
  名称：

  Analogues of thiolactomycin as potential anti-malarial and anti-trypanosomal agents

  摘要：

  A series of analogues of the naturally occurring antibiotic thiolactomycin (TLM) have been synthesised and evaluated for their ability to inhibit the growth of the malaria parasite, Plasmodium falciparum. Thiolactomycin is an inhibitor of Type II fatty acid synthase which is found in plants and most prokaryotes, but not an inhibitor of Type I fatty acid synthase in mammals. A number of the analogues showed inhibition equal to or greater than TLM. The introduction of hydrophobic alkyl groups at the C3 and C5 positions of the thiolactone ring lead to increased inhibition, the best showing a fourteenfold increase in activity over TLM. In addition, some of the analogues showed activity when assayed against the parasitic protozoa, Trypanosoma cruzi and Trypanosoma brucei. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2003.11.023

文献信息

• Structure−Activity Relationships at the 5-Position of Thiolactomycin:  An Intact (5<i>R</i>)-Isoprene Unit Is Required for Activity against the Condensing Enzymes from <i>Mycobacterium </i><i>t</i><i>uberculosis</i> and <i>Escherichia </i><i>c</i><i>oli</i>
  作者：Pilho Kim、Yong-Mei Zhang、Gautham Shenoy、Quynh-Anh Nguyen、Helena I. Boshoff、Ujjini H. Manjunatha、Michael B. Goodwin、John Lonsdale、Allen C. Price、Darcie J. Miller、Ken Duncan、Stephen W. White、Charles O. Rock、Clifton E. Barry、Cynthia S. Dowd

  DOI：10.1021/jm050825p

  日期：2006.1.1

  Thiolactomycin inhibits bacterial cell growth through inhibition of the beta-ketoacyl-ACP synthase activity of type II fatty acid synthases. The effect of modifications of the 5-position isoprenoid side chain on both IC(50) and MIC were determined. Synthesis and screening of a structurally diverse set of 5-position analogues revealed very little tolerance for substitution in purified enzyme assays, but a few analogues retained MIC, presumably through another target. Even subtle modifications such as reducing one or both double bonds of the diene were not tolerated. The only permissible structural modifications were removal of the isoprene methyl group or addition of a methyl group to the terminus. Cocrystallization of these two inhibitors with the condensing enzyme from Escherichia coli revealed that they retained the TLM binding mode at the active site with reduced affinity. These results suggest a strict requirement for a conjugated, planar side chain inserting within the condensing enzyme active site.