[6R-[6alpha,7beta(R*)]]-3-(乙酰氧基甲基)-7-(羟基苯基乙酰氨基)-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸 | 51818-85-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 中文名称: [6R-[6alpha,7beta(R*)]]-3-(乙酰氧基甲基)-7-(羟基苯基乙酰氨基)-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸
• 中文别名: 乙基α-乙基-1-羟基环己乙酸酯
• 英文名称: 7-[(1-hydroxy-1-phenyl)-acetamido]-3-acetoxymethyl-Δ³-cephem-4-carboxylic acid
• 英文别名: (2'R,6R,7R)-3-acetoxymethyl-7-hydroxy(phenyl)acetylaminoceph-3-em-4-carboxylic acid；(6R)-3-acetoxymethyl-7t-((R)-2-hydroxy-2-phenyl-acetylamino)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid；7β-((R)-2-hydroxy-2-phenyl-acetylamino)-cephalosporanic acid；7-Mandelamidocephalosporansaeure；[6R-[6alpha,7beta(R*)]]-3-(acetoxymethyl)-7-(hydroxyphenylacetamido)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid；(6R,7R)-3-(acetyloxymethyl)-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid
• CAS: 51818-85-0
• 化学式: C₁₈H₁₈N₂O₇S
• 分子量: 406.416
• InChiKey: CNAGMNMBHMQZPF-SUYBPPKGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [6R-[6alpha,7beta(R*)]]-3-(乙酰氧基甲基)-7-(羟基苯基乙酰氨基)-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸 在 次氯酸叔丁酯 、 lithium methanolate 、 potassium hydrogencarbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.58h， 生成 4-nitrobenzyl (5'R,6R,7S)-3-acetoxy-4'-oxo-5'-phenylspiro(1',3'-oxazolidine-2',7-ceph-3-em)-4-carboxylate
  参考文献：
  名称：

  Sammes, Peter G.; Smith, Steven; Ross, Barry C., Journal of the Chemical Society. Perkin transactions I, 1984, p. 2117 - 2124

  摘要：

  DOI：
• 作为产物：
  描述：

  R)-(-)-O-甲酰基扁桃酸酰氯 在 potassium hydrogencarbonate 作用下， 以 甲醇 、 水 、 丙酮 为溶剂， 反应 9.0h， 生成 [6R-[6alpha,7beta(R*)]]-3-(乙酰氧基甲基)-7-(羟基苯基乙酰氨基)-8-氧代-5-硫杂-1-氮杂双环[4.2.0]辛-2-烯-2-羧酸
  参考文献：
  名称：

  Sammes, Peter G.; Smith, Steven; Ross, Barry C., Journal of the Chemical Society. Perkin transactions I, 1984, p. 2117 - 2124

  摘要：

  DOI：

文献信息

• Modulation of the Microenvironment Surrounding the Active Site of Penicillin G Acylase Immobilized on Acrylic Carriers Improves the Enzymatic Synthesis of Cephalosporins
  作者：Paolo Bonomi、Teodora Bavaro、Immacolata Serra、Auro Tagliani、Marco Terreni、Daniela Ubiali

  DOI：10.3390/molecules181114349

  日期：——

  The catalytic properties of penicillin G acylase (PGA) from Escherichia coli in kinetically controlled synthesis of β-lactam antibiotics are negatively affected upon immobilization on hydrophobic acrylic carriers. Two strategies have been here pursued to improve the synthetic performance of PGA immobilized on epoxy-activated acrylic carriers. First, an aldehyde-based spacer was inserted on the carrier surface by glutaraldehyde activation (immobilization yield = 50%). The resulting 3-fold higher synthesis/hydrolysis ratio (vs/vh1 = 9.7 ± 0.7 and 10.9 ± 0.7 for Eupergit® C and Sepabeads® EC-EP, respectively) with respect to the unmodified support (vs/vh1 = 3.3 ± 0.4) was ascribed to a facilitated diffusion of substrates and products as a result of the increased distance between the enzyme and the carrier surface. A second series of catalysts was prepared by direct immobilization of PGA on epoxy-activated acrylic carriers (Eupergit® C), followed by quenching of oxiranes not involved in the binding with the protein with different nucleophiles (amino acids, amines, amino alcohols, thiols and amino thiols). In most cases, this derivatization increased the synthesis/hydrolysis ratio with respect to the non derivatized carrier. Particularly, post-immobilization treatment with cysteine resulted in about 2.5-fold higher vs/vh1 compared to the untreated biocatalyst, although the immobilization yield decreased from 70% (untreated Eupergit® C) to 20%. Glutaraldehyde- and cysteine-treated Eupergit® C catalyzed the synthesis of cefazolin in 88% (±0.9) and 87% (±1.6) conversion, respectively, whereas untreated Eupergit® C afforded this antibiotic in 79% (±1.2) conversion.

  大肠杆菌青霉素G酰化酶（PGA）的催化性质在动力学控制的β-内酰胺抗生素合成中，当其固定在疏水性丙烯酸载体上时会受到负面影响。本文采用两种策略来提高PGA固定在环氧活化丙烯酸载体上的合成性能。首先，通过戊二醛活化在载体表面插入基于醛基的间隔臂（固定化产率为50%）。与未修饰的载体相比，所得到的合成/水解比（vs/vh1）提高了3倍（分别为Eupergit® C和Sepabeads® EC-EP的9.7±0.7和10.9±0.7），这归因于由于酶与载体表面之间的距离增加，使得底物和产物的扩散更加容易。第二种催化剂系列是通过将PGA直接固定在环氧活化的丙烯酸载体（Eupergit® C）上，然后使用不同亲核试剂（氨基酸、胺、氨基醇、硫醇和氨基硫醇）淬灭未与蛋白质结合的环氧乙烷来制备的。在大多数情况下，这种衍生化相比于非衍生化载体增加了合成/水解比。特别是，用半胱氨酸进行后固定化处理使得vs/vh1比未处理的生物催化剂提高了约2.5倍，尽管固定化产率从70%（未处理的Eupergit® C）降至20%。经过戊二醛和半胱氨酸处理的Eupergit® C催化头孢唑啉的合成转化率分别为88%（±0.9）和87%（±1.6），而未处理的Eupergit® C则达到79%（±1.2）的转化率。
• Influence of Substrate Structure on PGA-Catalyzed Acylations. Evaluation of Different Approaches for the Enzymatic Synthesis of Cefonicid
  作者：Marco Terreni、Joseph Gapesie Tchamkam、Umberto Sarnataro、Silvia Rocchietti、Roberto Fernández-Lafuente、José M. Guisán

  DOI：10.1002/adsc.200404136

  日期：2005.1

  centre of PGA. The enzymatic acylation of these nuclei with R-methyl mandelate has been studied in order to evaluate different approaches for the enzymatic synthesis of cefonicid. The best results have been obtained in the acylation of 7-SACA. Cefonicid (8) was recovered from the reaction mixture as the disodium salt in 65% yield and about 95% of purity. Furthermore, through acylation of 7-ACA, a “one-pot”

  研究了底物结构对大肠杆菌中动态控制的酰化反应中青霉素G酰基转移酶（PGA）催化性能的影响。特别地，已经考虑了合成速率（v s）与酰化酯的水解速率（v h1）之间的比率，评估了不同的β-内酰胺核对活性位点的亲和力。7-氨基头孢烷酸（7-ACA）和7-氨基-3-（1-磺甲基-1,2,3,4-四唑-5-基）硫甲基-3-头孢4-4-羧酸（7-SACA）对PGA的活性中心表现出良好的亲和力。这些核被R酶促酰化对扁桃酸甲酯进行了研究，以评估头孢烯酮酶促合成的不同方法。在7-SACA的酰化中已获得最好的结果。从反应混合物中以二钠盐的形式回收头孢烯酮（8），产率为65％，纯度为约95％。此外，通过7-ACA的酰化反应，从头孢菌素C开始，使用三种酶依次进行了“一锅法”化学酶合成：D-氨基酸氧化酶（DAO），戊二酰酰基化酶（GA）和PGA。分三步获得头孢烯二钠盐，避免了任何中间纯化，总产率为35％，纯度为约9
• Coupling of Site-Directed Mutagenesis and Immobilization for the Rational Design of More Efficient Biocatalysts: The Case of Immobilized 3G3K PGA from<i>E.</i><i>coli</i>
  作者：Immacolata Serra、Davide A. Cecchini、Daniela Ubiali、Elena M. Manazza、Alessandra M. Albertini、Marco Terreni

  DOI：10.1002/ejoc.200801204

  日期：2009.3

  We have investigated the synthetic performance of the immobilized 3G3K mutant of the Penicillin G acylase (PGA) from E. coli obtained by site-directed mutagenesis. The 3G3K mutant, characterized by a tag consisting of three lysines alternating with three glycines at the end of the β-chain, has previously been reported to have a higher ratio for the rate of antibiotic synthesis and the rate of hydrolysis

  我们研究了通过定点诱变获得的来自大肠杆菌的青霉素 G 酰基转移酶 (PGA) 的固定化 3G3K 突变体的合成性能。3G3K 突变体的特征是由三个赖氨酸与 β 链末端的三个甘氨酸交替组成的标签，之前曾报道过抗生素合成速率和酰化剂水解速率的比率更高。 vs/vh1 值）比野生型酶。通过使用不同的乙醛基支持物（用醛基激活），对 3G3K 突变体进行了新的固定研究。在通过动力学控制的 N-酰化 (kcNa) 合成头孢曼多和头孢尼西的过程中测试了新固定化制剂的催化性能。与商业野生型 PGA 相比，
• Semisynthetic cephalosporins. Synthesis and structure-activity relations of 7-mandelamido-3-cephem-4-carboxylic acids
  作者：J. R. E. Hoover、G. L. Dunn、D. R. Jakas、L. L. Lam、J. J. Taggart、J. R. Guarini、L. Phillips

  DOI：10.1021/jm00247a008

  日期：1974.1
• Modulation of penicillin acylase properties via immobilization techniques: one-pot chemoenzymatic synthesis of cephamandole from cephalosporin C
  作者：Marco Terreni、Giuseppe Pagani、Daniela Ubiali、Roberto Fernández-Lafuente、Cesar Mateo、José M. Guisán

  DOI：10.1016/s0960-894x(01)00463-2

  日期：2001.9

  The modulation of penicillin G acylase (PGA) properties via immobilization techniques has been performed studying the acylation of 7-aminocephalosporanic acid with R-mandelic acid methyl ester. PGA from Escherichia coli, immobilized onto agarose activated with glycidol (glyoxyl-agarose), has been used for the design of a novel one-pot synthesis of Cephamandole in aqueous medium and without isolation of intermediates, through three consecutive biotransformations catalyzed by D-amino acid oxidase, glutaryl acylase and PGA. (C) 2001 Elsevier Science Ltd. All rights reserved.