(R)-2-mercapto-3-phenylacetic acid (R-thiomandelic acid) | 16201-51-7

• 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: (R)-2-mercapto-3-phenylacetic acid (R-thiomandelic acid)
• 英文别名: (R)-2-phenyl-2-sulfanylacetic acid；(R)-Thiomandelsaeure；thiomandelic acid；(R)-mercapto-phenyl-acetic acid；(R)-α-Mercapto-phenylessigsaeure；D-α-thio-mandelic acid；(2r)-Phenyl(Sulfanyl)ethanoic Acid；(2R)-2-phenyl-2-sulfanylacetic acid
• CAS: 16201-51-7
• 化学式: C₈H₈O₂S
• 分子量: 168.216
• InChiKey: QYIGFZOHYGYBLX-SSDOTTSWSA-N

物化性质

• 沸点：
  290.6±28.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  38.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-mercapto-3-phenylacetic acid (R-thiomandelic acid) 在 碘 作用下， 以 水 、 乙腈 为溶剂， 生成 (+)-2,2'-diphenyl-2,2'-dithiobisacetic acid
  参考文献：
  名称：

  Thiol-Containing Metallo-β-Lactamase Inhibitors Resensitize Resistant Gram-Negative Bacteria to Meropenem

  摘要：

  The prevalence of infections caused by metallo-beta-lactamase (MBL) expressing Gram-negative bacteria has grown at an alarming rate in recent years. Despite the fact that MBLs can deactivate virtually all beta-lactam antibiotics, there are as of yet no approved drugs available that inhibit their activity. We here examine the ability of previously reported thiol-based MBL inhibitors to synergize with meropenem and cefoperazone against a panel of Gram-negative carbapenem-resistant isolates expressing different beta-lactamases. Among the compounds tested, thiomandelic acid 3 and 2-mercapto-3-phenylpropionic acid 4 were found to efficiently potentiate the activity of meropenem, especially against an imipenemase (IMP) producing strain of K. pneumoniae. In light of the zinc-dependent hydrolytic mechanism employed by MBLs, biophysical studies using isothermal titration calorimetry were also performed, revealing a correlation between the synergistic activity of thiols 3 and 4 and their zinc-binding ability with measured K-d values of 9.8 and 20.0 mu M, respectively.

  DOI：

  10.1021/acsinfecdis.7b00094
• 作为产物：
  描述：

  D-(-)-扁桃酸乙酯 在 盐酸 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 118.33h， 生成 (R)-2-mercapto-3-phenylacetic acid (R-thiomandelic acid)
  参考文献：
  名称：

  Synthesis of (racemization prone) optically active thiols by SN2 substitution using cesium thiocarboxylates

  摘要：

  DOI：

  10.1021/jo00369a020

文献信息

• Chiral syntheses of methyl (<i>R</i> )-2-Sulfanylcarboxylic esters and acids with optical purity determination using HPLC
  作者：Ryosuke Sasaki、Yoo Tanabe

  DOI：10.1002/chir.22860

  日期：2018.6

  Accessible chiral syntheses of 3 types of (R)‐2‐sulfanylcarboxylic esters and acids were performed: (R)‐2‐sulfanylpropanoic (thiolactic) ester (53%, 98%ee) and acid (39%, 96%ee), (R)‐2‐sulfanylsucciinic diester (59%, 96%ee), and (R)‐2‐mandelic ester (78%, 90%ee) and acid (59%, 96%ee). The present practical and robust method involves (i) clean SN2 displacement of methanesulfonates of (S)‐2‐hydroxyesters

  进行了3种类型的（R）-2-硫烷基羧酸酯和酸的可手性合成：（R）-2-硫烷基丙酸（巯基乳酸）酯（53％，98％ee）和酸（39％，96％ee）， （R）-2-磺酰基琥珀酸二酯（59％，96％ee）和（R）-2-扁桃酸酯（78％，90％ee）和酸（59％，96％ee）。本实用且稳健的方法涉及（i）使用具有三（2- [2- [2-甲氧基乙氧基]）乙胺的市售AcSK清洁（S）-2-羟基酯的甲磺酸盐的S N 2置换和（ii）足够温和的脱乙酰基作用。光学纯度由相应的（2 R，5 R）-反式确定噻唑烷酮-4-酮和（2 S，5 R）顺式噻唑烷酮-4-酮衍生物基于高精度高效液相色谱分析，具有较高的分离度。与报道的利用AcSCs（由AcSH和CsCO 3产生）的方法相比，本方法具有多个优点，即使用无味的AcCOSK试剂，合理的反应速度，分离步骤以及准确，可靠的光学纯度测定。
• Synthesis and determination of enantiomeric excesses of non-racemic tert-thiols derived from chiral secondary α-mercaptocarboxylic acids
  作者：Bert Strijtveen、Richard M. Kellogg

  DOI：10.1016/s0040-4020(01)87682-1

  日期：1987.1

  optically active without employment of a chiral auxiliary. Their enantiomeric excesses were determined by esterification, conversion to diasterecomeric phosphonodithioates on reaction with-31CH3-POCl2, followed by integration of the well separated proton-decoupled P NMR signals. This is apparently the first example of enantiomeric excess determinations of chiral tertiary thiols.

  已经制备了丙酸，3-苯基丙酸，2-苯基乙酸，3-甲基丁酸，4-甲基戊酸和（S）-3-甲基戊酸的旋光α-巯基衍生物。这些酸与新戊醛缩合得到2-叔丁基-5-取代的1,3-氧杂硫杂环戊酮（）；的形成在过量几何异构体并获得通过结晶纯。对于5-苄基衍生物（），主要的非对映异构体的排列通过X射线晶体学确定。这些-二取代的杂环（），在用二异丙基丙酰胺锂（LDA）或六甲基二硅叠氮化锂（LHMDS）进行质子化后，随后与亲电子试剂如卤代烷，醛或酮的亲电反应，在水解后以高对映体过量的形式提供α-支链的α-巯基羧酸或酯（）。这些是由于α-位置上的质子被羰基整体取代而保持构型且没有外消旋作用。该立体化学过程是通过晶体结构确定（2S）-的方法确定的（2S）-是由-5-苯基-1,3-氧杂噻喃-4-酮（）。无需使用手性助剂即可获得具有光学活性的叔α-巯基羧酸。通过酯化，与31 CH 3 -POCl 2反应转化为非对映体膦
• Highly Enantioselective Reaction of α-Lithio 2-Quinolyl Sulfide Using Chiral Bis(oxazoline)s: A New Synthesis of Enantioenriched Thiols
  作者：Shuichi Nakamura、Akinori Furutani、Takeshi Toru

  DOI：10.1002/1099-0690(200205)2002:10<1690::aid-ejoc1690>3.0.co;2-9

  日期：2002.5

  The enantioselective reaction of α-lithio benzyl 2-quinolyl sulfide proceeds through a dynamic thermodynamic resolution pathway, giving the products with high stereoselectivity. The products afford chiral thiols without racemization upon removal of the quinolyl group. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

  α-硫代苄基2-喹啉硫醚的对映选择性反应通过动态热力学拆分途径进行，从而使产物具有较高的立体选择性。除去喹啉基后，该产物提供手性硫醇而不消旋。（©Wiley-VCH Verlag GmbH，69451 Weinheim，Germany，2002）
• Gerlach, Uwe; Haubenreich, Thomas; Huenig, Siegfried, Chemische Berichte, 1994, vol. 127, # 10, p. 1969 - 1980
  作者：Gerlach, Uwe、Haubenreich, Thomas、Huenig, Siegfried

  DOI：——

  日期：——
• Thiol-Containing Metallo-β-Lactamase Inhibitors Resensitize Resistant Gram-Negative Bacteria to Meropenem
  作者：Kamaleddin Haj Mohammad Ebrahim Tehrani、Nathaniel I. Martin

  DOI：10.1021/acsinfecdis.7b00094

  日期：2017.10.13

  The prevalence of infections caused by metallo-beta-lactamase (MBL) expressing Gram-negative bacteria has grown at an alarming rate in recent years. Despite the fact that MBLs can deactivate virtually all beta-lactam antibiotics, there are as of yet no approved drugs available that inhibit their activity. We here examine the ability of previously reported thiol-based MBL inhibitors to synergize with meropenem and cefoperazone against a panel of Gram-negative carbapenem-resistant isolates expressing different beta-lactamases. Among the compounds tested, thiomandelic acid 3 and 2-mercapto-3-phenylpropionic acid 4 were found to efficiently potentiate the activity of meropenem, especially against an imipenemase (IMP) producing strain of K. pneumoniae. In light of the zinc-dependent hydrolytic mechanism employed by MBLs, biophysical studies using isothermal titration calorimetry were also performed, revealing a correlation between the synergistic activity of thiols 3 and 4 and their zinc-binding ability with measured K-d values of 9.8 and 20.0 mu M, respectively.