2,2,2-trichloroethyl-phenyl acetate | 113266-89-0

• 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: 2,2,2-trichloroethyl-phenyl acetate
• 英文别名: 2,2,2-trichloroethyl-(3-benzyloxycarbonyl)phenylacetate；Benzyl 3-[2-oxo-2-(2,2,2-trichloroethoxy)ethyl]benzoate
• CAS: 113266-89-0
• 化学式: C₁₈H₁₅Cl₃O₄
• 分子量: 401.674
• InChiKey: VJHKIHMEHIARHT-UHFFFAOYSA-N

物化性质

• 沸点：
  538.7±50.0 °C(predicted)
• 密度：
  1.377±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,2,2-trichloroethyl-phenyl acetate 在 DMF 氟化铵 、 草酰氯 、 氢氟酸 、 sodium hexamethyldisilazane 、 溶剂黄146 、 三氟乙酸 、 锌 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.75h， 生成 cis-1-[3'-(benzyloxycarbonyl)phenylacetate]-4-(4'-carboxybenzyloxycarbonyl)-3-(4'-hydroxybenzyl)-2-azetidionone
  参考文献：
  名称：

  Design, Synthesis, and Proposed Active Site Binding Analysis of Monocyclic 2-Azetidinone Inhibitors of Prostate Specific Antigen

  摘要：

  A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC50 = 8.98 +/- 0.90 muM) which was used as a lead compound in this study. A single low energy conformation structure II (Figure 2) was adopted as most likely to represent binding after minimization and dynamics calculations. Systematic analysis of the binding importance of all three side chains appended to the 2-azetidinone was conducted by the synthesis of several analogues. A proposed salt bridge to Lys-145 with 4 (IC50 = 5.84 +/- 0.92 muM) gave improved inhibition, but generally the binding of the N-1 side chain in a specific secondary aromatic binding site did not tolerate much structural alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6 (IC50 = 1.43 +/- 0.19 muM), and polar functionality could also be added in a proposed interaction with Gln-166 in 5 (IC50 = 1.34 +/- 0.05 muM). Reversal of the C-4 ester connectivity furnished inhibitors 7 (IC50 = 1 59 +/- 0 15 muM), 11 (IC50 = 3.08 +/- 0.41 muM), and 13 (IC50 = 2.19 +/- 0.36 muM) which were perceived to bind to PSA by a rotation of 180 degrees relative to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality into the C-3 side chain provided 16 (IC50 = 348 +/- 50 nM) with the greatest increase in PSA inhibition by a single modification. Multiple copy simultaneous search (MCSS) analysis of the PSA active site further supported our model and suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC50 = 226 +/- 10 nM) as the most potent inhibitor of PSA reported to date. It is concluded that our design approach has been successful in developing PSA inhibitors and could also be applied to the inhibition of other enzymes, especially in the absence of crystallographic information.

  DOI：

  10.1021/jm000145g
• 作为产物：
  描述：

  间苯二甲酸 在 氢氧化钾 、 氯化亚砜 作用下， 以 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 3.0h， 生成 2,2,2-trichloroethyl-phenyl acetate
  参考文献：
  名称：

  An efficient substitute for the α-amimoadipoyl moiety of δ-(-α-aminloadipoytl)--cisteintl--valine in the emzymatic synthesis of penicillins

  摘要：

  DOI：

  10.1016/s0040-4020(01)83463-3

文献信息

• Enzymatic process for B-Lactams
  申请人：THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

  公开号：EP0260778A1

  公开（公告）日：1988-03-23

  N-(3-Carboxyphenylacetyl)-L-cysteinyl-D-valine and N-(3--carboxyphenylacetyl)-L-cysteinyl-D-modified-valine dipeptides are substrates for isopenicillin N synthetase conversion to penams e.g. 2-vinyl-2-methylpenam, 2-allenylpenam and 2-methoxypenam. The substitution of the 3-carboxyphenylacetyl group for the 2-a-aminoadipoyl group of the natural tripeptide L-AAA-L-cys-D-val and tripeptides with modified valine affords efficient conversion to the penams.

  N-(3-羧基苯乙酰基)-L-半胱氨酰-D-缬氨酸和 N-(3-羧基苯乙酰基)-L-半胱氨酰-D-改性缬氨酸二肽是异青霉素 N 合成酶转化为戊酰胺（如 2-乙烯基-2-甲基戊酰胺、2-阿仑基戊酰胺和 2-甲氧基戊酰胺）的底物。 用 3-羧基苯乙酰基取代天然三肽 L-AAA-L-cys-D-val 和具有改性缬氨酸的三肽中的 2-a-氨基联二酰基，可有效地转化为戊酰胺。
• Enzymatic process for 3-substituted cephalosporins
  申请人：THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD

  公开号：EP0268343B1

  公开（公告）日：1992-05-27
• An efficient substitute for the α-amimoadipoyl moiety of δ-(-α-aminloadipoytl)--cisteintl--valine in the emzymatic synthesis of penicillins
  作者：Jack E. Baldwin、Robert M. Adlington、M.James C. Crabbe、Takashi Nomoto、Christopher J. Schofield

  DOI：10.1016/s0040-4020(01)83463-3

  日期：1987.1
• BALDWIN, JACK E.;ADLINGTON, ROBERT M.;CRABBE, M. JAMES C.;NOMOTO, TAKASHI+, TETRAHEDRON, 43,(1987) N 18, 4217-4220
  作者：BALDWIN, JACK E.、ADLINGTON, ROBERT M.、CRABBE, M. JAMES C.、NOMOTO, TAKASHI+

  DOI：——

  日期：——
• Design, Synthesis, and Proposed Active Site Binding Analysis of Monocyclic 2-Azetidinone Inhibitors of Prostate Specific Antigen
  作者：Robert M. Adlington、Jack E. Baldwin、Gerald W. Becker、Beining Chen、Leifeng Cheng、Stephen L. Cooper、Robert B. Hermann、Trevor J. Howe、William McCoull、Ann M. McNulty、Blake L. Neubauer、Gareth J. Pritchard

  DOI：10.1021/jm000145g

  日期：2001.5.1

  A homology derived molecular model of prostate specific antigen (PSA) was created and refined. The active site region was investigated for specific interacting functionality and a binding model postulated for the novel 2-azetidinone acyl enzyme inhibitor 1 (IC50 = 8.98 +/- 0.90 muM) which was used as a lead compound in this study. A single low energy conformation structure II (Figure 2) was adopted as most likely to represent binding after minimization and dynamics calculations. Systematic analysis of the binding importance of all three side chains appended to the 2-azetidinone was conducted by the synthesis of several analogues. A proposed salt bridge to Lys-145 with 4 (IC50 = 5.84 +/- 0.92 muM) gave improved inhibition, but generally the binding of the N-1 side chain in a specific secondary aromatic binding site did not tolerate much structural alteration. A hydrophobic interaction of the C-4 side chain afforded inhibitor 6 (IC50 = 1.43 +/- 0.19 muM), and polar functionality could also be added in a proposed interaction with Gln-166 in 5 (IC50 = 1.34 +/- 0.05 muM). Reversal of the C-4 ester connectivity furnished inhibitors 7 (IC50 = 1 59 +/- 0 15 muM), 11 (IC50 = 3.08 +/- 0.41 muM), and 13 (IC50 = 2.19 +/- 0.36 muM) which were perceived to bind to PSA by a rotation of 180 degrees relative to the C-4 ester of normal connectivity. Incorporation of hydroxyl functionality into the C-3 side chain provided 16 (IC50 = 348 +/- 50 nM) with the greatest increase in PSA inhibition by a single modification. Multiple copy simultaneous search (MCSS) analysis of the PSA active site further supported our model and suggested that 18 would bind strongly. Asymmetric synthesis yielded 18 (IC50 = 226 +/- 10 nM) as the most potent inhibitor of PSA reported to date. It is concluded that our design approach has been successful in developing PSA inhibitors and could also be applied to the inhibition of other enzymes, especially in the absence of crystallographic information.