diphenylmethyl 6α-(hydroxymethyl)penicillanate | 81324-18-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diphenylmethyl 6α-(hydroxymethyl)penicillanate
• 英文别名: benzhydryl (2S,5R,6S)-6-(hydroxymethyl)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate
• CAS: 81324-18-7
• 化学式: C₂₂H₂₃NO₄S
• 分子量: 397.495
• InChiKey: YTVFRYLIDPMGDF-XKGZKEIXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diphenylmethyl 6α-(hydroxymethyl)penicillanate 在 4-二甲氨基吡啶 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 乙腈 为溶剂， 反应 4.0h， 生成 (2S,5R,6R)-6-Mercaptomethyl-3,3-dimethyl-7-oxo-4-thia-1-aza-bicyclo[3.2.0]heptane-2-carboxylic acid benzhydryl ester
  参考文献：
  名称：

  青霉素衍生的抑制剂同时靶向金属和丝氨酸-β-内酰胺酶。

  摘要：

  描述了四种6-（巯基甲基）青霉酸酯和四种相应的6-（羟甲基）青霉酸酯的合成和β-内酰胺酶抑制活性。这些青霉素包括C6立体异构体以及戊二噻唑烷硫的硫化物和砜的氧化态。评价所有化合物作为代表性金属-和丝氨酸-β-内酰胺酶的抑制剂。显示选择的（巯基甲基）青霉酸酯可灭活金属-和丝氨酸-β-内酰胺酶，并显示出与哌拉西林对产生β-内酰胺酶的菌株的协同作用。

  DOI：

  10.1016/j.bmcl.2003.12.037
• 作为产物：
  描述：

  (2S,5R)-6,6-dibromo-3,3-dimethyl-4,4,7-trioxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid diphenylmethyl ester 在 三丁基膦 、 叔丁基氯化镁 作用下， 以 甲醇 为溶剂， 生成 diphenylmethyl 6α-(hydroxymethyl)penicillanate
  参考文献：
  名称：

  6-(1-hydroxyalkyl)penam sulfone derivatives as inhibitors of class a and class C β-lactamases I

  摘要：

  Five 6-(1-hydroxyalkyl)penam sulfone derivatives and two 6-(hydroxymethyl)penams were synthesized for beta-lactamase inhibitor screens. The substituent effects and stereochemical requirements of 6 alpha- and 6 beta-(1-hydroxyalkyl) groups for the biological activity of penam sulfone derivatives were investigated. Of these substituents, only the 6 beta-hydroxymethyl group of 15 improved the activity of sulbactam against both TEM-1 and AmpC beta-lactamases. The sulfone moiety is required for the enhancement of the beta-lactamase inhibitory activity. 6 beta-Hydroxymethylsulbactam (15) was able to restore the activity of piperacillin in vitro and in vivo against various beta-lactamase producing microorganisms. (C) 1999 Elsevier Science Ctd. All rights reserved.

  DOI：

  10.1016/s0960-894x(99)00106-7

文献信息

• Stereoselective Reduction of α-Bromopenicillanates by Tributylphosphine
  作者：Akihiro Ishiwata、Lakshmi P. Kotra、Kazuyuki Miyashita、Tsuyoshi Nagase、Shahriar Mobashery

  DOI：10.1021/ol000185e

  日期：2000.9.1

  [reaction: see text] Diastereoselective reduction of 6-bromo-6-substituted penicillanate esters has been achieved by treatment with tributylphosphine to give 6-substituted penicillanate esters. This reaction would appear to proceed through a phosphonium beta-lactam enolate species, followed by a diastereoselective protonation. This method has the advantage of being simple to carry out and it is mild

  [反应：见正文]通过用三丁基膦处理得到6-取代的青霉酸酯，已经实现了6-溴-6-取代的青霉酸酯的非对映选择性还原。该反应似乎通过through-β-内酰胺烯醇化species物种进行，随后是非对映选择性质子化。该方法的优点是易于实施，并且温和，非对映选择性高，并且应能耐受底物中的许多官能团。这些意见的含义进行了讨论。
• 6-(1-hydroxyalkyl)penam sulfone derivatives as inhibitors of class a and class C β-lactamases I
  作者：Panayota Bitha、Zhong Li、Gerardo D. Francisco、Beth A. Rasmussen、Yang-I Lin

  DOI：10.1016/s0960-894x(99)00106-7

  日期：1999.4

  Five 6-(1-hydroxyalkyl)penam sulfone derivatives and two 6-(hydroxymethyl)penams were synthesized for beta-lactamase inhibitor screens. The substituent effects and stereochemical requirements of 6 alpha- and 6 beta-(1-hydroxyalkyl) groups for the biological activity of penam sulfone derivatives were investigated. Of these substituents, only the 6 beta-hydroxymethyl group of 15 improved the activity of sulbactam against both TEM-1 and AmpC beta-lactamases. The sulfone moiety is required for the enhancement of the beta-lactamase inhibitory activity. 6 beta-Hydroxymethylsulbactam (15) was able to restore the activity of piperacillin in vitro and in vivo against various beta-lactamase producing microorganisms. (C) 1999 Elsevier Science Ctd. All rights reserved.
• Penicillin-derived inhibitors that simultaneously target both metallo- and serine-β-lactamases
  作者：John D. Buynak、Hansong Chen、Lakshminaryana Vogeti、Venkat Rao Gadhachanda、Christine A. Buchanan、Timothy Palzkill、Robert W. Shaw、James Spencer、Timothy R. Walsh

  DOI：10.1016/j.bmcl.2003.12.037

  日期：2004.3

  The synthesis and beta-lactamase inhibitory activity of four 6-(mercaptomethyl)penicillinates and the four corresponding 6-(hydroxymethyl)penicillinates are described. These penicillins include both C6 stereoisomers as well as the sulfide and sulfone oxidation states of the penam thiazolidine sulfur. All compounds were evaluated as inhibitors of representative metallo- and serine-beta-lactamases enzymes

  描述了四种6-（巯基甲基）青霉酸酯和四种相应的6-（羟甲基）青霉酸酯的合成和β-内酰胺酶抑制活性。这些青霉素包括C6立体异构体以及戊二噻唑烷硫的硫化物和砜的氧化态。评价所有化合物作为代表性金属-和丝氨酸-β-内酰胺酶的抑制剂。显示选择的（巯基甲基）青霉酸酯可灭活金属-和丝氨酸-β-内酰胺酶，并显示出与哌拉西林对产生β-内酰胺酶的菌株的协同作用。