(+/-)-5-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one | 873801-69-5

• 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-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one
• 英文别名: 3,5-dimethyl-5-hydroxymethyl-4-methoxymethoxy-5H-thiophen-2-one；5-(Hydroxymethyl)-4-(methoxymethoxy)-3,5-dimethylthiophen-2-one
• CAS: 873801-69-5
• 化学式: C₉H₁₄O₄S
• 分子量: 218.274
• InChiKey: YIULPYQSQOPDRK-UHFFFAOYSA-N

物化性质

• 沸点：
  376.5±42.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  81.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-5-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one 在 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one
  参考文献：
  名称：

  Novel route to 5-position vinyl derivatives of thiolactomycin: olefination versus deformylation

  摘要：

  Vinyl and diene derivatives of thiolactomycin have been prepared via Horner-Wadsworth-Emmons olefination from protected 5-formyl-3,5-dimethylthiotetronic acid. Several 4-position protecting groups and a variety of phosphonates were evaluated, with MOM protection and beta-ketophosphonates yielding the highest ratio of the desired product to deformylated product. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2006.03.058
• 作为产物：
  描述：

  Methyl-γ-bromo-propyonyl propanate 在 氢氧化钾 、 三乙胺 、 N,N-二异丙基乙胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 21.5h， 生成 (+/-)-5-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one
  参考文献：
  名称：

  化学酶法合成（5 S）-和（5 R）-羟甲基-3,5-二甲基-4-（甲氧基甲氧基）-5 H-噻吩-2-酮：硫菌素的前体及其绝对构型的确定

  摘要：

  进行了方便的对映选择性合成的（5 S）-和（5 R）-羟甲基-3,5-二甲基-4-（甲氧基甲氧基）-5 H-噻吩-2-酮，它是硫代催乳素合成中的关键中间体通过番木瓜脂肪酶介导的拆分方案分离得到94％ee的（R）-2和98％ee的对映体（S）-9。C-5位置的绝对构型已通过Mosher的方法确定。

  DOI：

  10.1016/j.tetasy.2006.10.032

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.
• Novel route to 5-position vinyl derivatives of thiolactomycin: olefination versus deformylation
  作者：Pilho Kim、Clifton E. Barry、Cynthia S. Dowd

  DOI：10.1016/j.tetlet.2006.03.058

  日期：2006.5

  Vinyl and diene derivatives of thiolactomycin have been prepared via Horner-Wadsworth-Emmons olefination from protected 5-formyl-3,5-dimethylthiotetronic acid. Several 4-position protecting groups and a variety of phosphonates were evaluated, with MOM protection and beta-ketophosphonates yielding the highest ratio of the desired product to deformylated product. (c) 2006 Elsevier Ltd. All rights reserved.
• Chemoenzymatic synthesis of (5S)- and (5R)-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one: a precursor of thiolactomycin and determination of its absolute configuration
  作者：Ahmed Kamal、Ahmad Ali Shaik、Shaik Azeeza、M. Shaheer Malik、Mahendra Sandbhor

  DOI：10.1016/j.tetasy.2006.10.032

  日期：2006.11

  A convenient enantioselective synthesis of (5S)- and (5R)-hydroxymethyl-3,5-dimethyl-4-(methoxymethoxy)-5H-thiophen-2-one, a key intermediate in the synthesis of thiolactomycin has been carried out by a Carica papaya lipase-mediated resolution protocol to provide (R)-2 in a 94% ee and its enantiomer (S)-9 in a 98% ee. The absolute configuration at the C-5 position has been determined by Mosher’s method

  进行了方便的对映选择性合成的（5 S）-和（5 R）-羟甲基-3,5-二甲基-4-（甲氧基甲氧基）-5 H-噻吩-2-酮，它是硫代催乳素合成中的关键中间体通过番木瓜脂肪酶介导的拆分方案分离得到94％ee的（R）-2和98％ee的对映体（S）-9。C-5位置的绝对构型已通过Mosher的方法确定。