2-keto-3-(N-benzoyl-amino)-3-phenyl propionic acid ethyl ester | 153433-79-5

• 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-keto-3-(N-benzoyl-amino)-3-phenyl propionic acid ethyl ester
• 英文别名: 2-keto-3-(N-benzoylamino)-3-phenylpropionic acid, ethyl ester；ethyl 3-benzamido-2-oxo-3-phenylpropanoate；2-Keto-3-(N-benzoylamino)-3-phenyl propionic acid ethyl ester；2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester
• CAS: 153433-79-5
• 化学式: C₁₈H₁₇NO₄
• 分子量: 311.337
• InChiKey: WMZZOLWIFXPWPZ-UHFFFAOYSA-N

物化性质

• 沸点：
  525.7±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-keto-3-(N-benzoyl-amino)-3-phenyl propionic acid ethyl ester 在 hansenula polymorpha SC 13865 cells 作用下， 反应 48.0h， 以65%的产率得到(2R,3S)-3-(苯甲酰基氨基)-2-羟基苯丙酸乙酯
  参考文献：
  名称：

  Microbial synthesis of (2R,3S)-(−)-N-benzoyl-3-phenyl isoserine ethyl ester-a taxol side-chain synthon

  摘要：

  The chiral intermediate (2R,3S)-(-)-N-benzoyl-3-phenyl isoserine ethyl ester 2a, a potential taxol 5 side-chain synthon, was prepared by microbial and enzymatic processes. Taxol 5, is an anticancer compound recently approved by FDA for the treatment of ovarian cancer. The stereoselective reduction of racemic 2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester 1 to the corresponding alcohol 2 was carried out using microbial cultures. Among microorganisms evaluated, Hansenula polymorpha SC 13865 and Hansenula fabianii SC 13894 effectively reduced compound 1 to the desired syn diastereomer 2a. Reaction yields of >80% and enantiomeric excesses of >98% were observed for these bioreduction process. About 10-20% of anti diastereomers (2c,2d) were produced during bioreduction.

  DOI：

  10.1016/s0957-4166(00)82256-9
• 作为产物：
  描述：

  L-苯甘氨酸 在 4-二甲氨基吡啶 、 氢氧化钾 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 5.0h， 生成 2-keto-3-(N-benzoyl-amino)-3-phenyl propionic acid ethyl ester
  参考文献：
  名称：

  Microbial synthesis of (2R,3S)-(−)-N-benzoyl-3-phenyl isoserine ethyl ester-a taxol side-chain synthon

  摘要：

  The chiral intermediate (2R,3S)-(-)-N-benzoyl-3-phenyl isoserine ethyl ester 2a, a potential taxol 5 side-chain synthon, was prepared by microbial and enzymatic processes. Taxol 5, is an anticancer compound recently approved by FDA for the treatment of ovarian cancer. The stereoselective reduction of racemic 2-keto-3-(N-benzoylamino)-3-phenylpropionic acid ethyl ester 1 to the corresponding alcohol 2 was carried out using microbial cultures. Among microorganisms evaluated, Hansenula polymorpha SC 13865 and Hansenula fabianii SC 13894 effectively reduced compound 1 to the desired syn diastereomer 2a. Reaction yields of >80% and enantiomeric excesses of >98% were observed for these bioreduction process. About 10-20% of anti diastereomers (2c,2d) were produced during bioreduction.

  DOI：

  10.1016/s0957-4166(00)82256-9

文献信息

• Synthesis of four chiral pharmaceutical intermediates by biocatalysis
  作者：Ramesh N. Patel、Amit Banerjee、Laszlo J. Szarka

  DOI：10.1007/bf02546196

  日期：1995.11

  Chiral intermediates were prepared by biocatalytic processes for the chemical synthesis of four pharmaceutical drug candidates. These include: (i) the microbial reduction of 3,5‐dioxo‐6‐(benzyloxy) hexanoic ethyl ester to (3S,5R)‐dihydroxy‐6‐(benzyloxy) hexanoic acid ethyl ester, an intermediate for a new anticholesterol drug; (ii) synthesis of (2R,3S)‐(‐)‐N‐benzoyl‐3‐phenyl isoserine ethyl ester, a taxol side‐chain synthon; (iii) the microbial oxygenation of 2,2‐dimethyl‐2H‐1‐benzopyran‐6‐carbonitrile to the corresponding (3S,4S) epoxide and (3S,4R)‐trans diol, intermediates for synthesis of potassium channel opener; (iv) the biotransformation of (exo,exo)‐7‐oxabicyclo [2.2.1] heptane‐2,3‐dimethanol to the corresponding chiral lactol and lactone, intermediates for thromboxane A₂ antagonist.

  摘要 通过生物催化过程制备了手性中间体，用于四种候选药物的化学合成。这些中间体包括(i) 微生物将 3,5-二氧代-6-（苄氧基）己酸乙酯还原为(3S,5R)-二羟基-6-（苄氧基）己酸乙酯，这是一种新型抗胆固醇药物的中间体；(ii) 合成(2R,3S)-(-)-N-苯甲酰基-3-苯基异丝氨酸乙酯，这是一种紫杉醇侧链合成物；(iii) 微生物氧合 2,2-二甲基-2H-1-苯并吡喃-6-甲腈，生成相应的(3S,4S) 环氧化物和(3S,4R)-反式二醇，这是合成钾通道开放剂的中间体；(iv) 生物转化(exo,exo)-7-氧杂双环[2.2.1]庚烷-2,3-二甲醇的生物转化，生成相应的手性内醇和内酯，这是血栓素 A2 拮抗剂的中间体。
• Chemo- and biocatalytic strategies to obtain phenylisoserine, a lateral chain of Taxol by asymmetric reduction
  作者：Isabella Rimoldi、Michela Pellizzoni、Giorgio Facchetti、Francesco Molinari、Daniele Zerla、Raffaella Gandolfi

  DOI：10.1016/j.tetasy.2011.11.017

  日期：2011.12

  via asymmetric reduction with transition metal–diphoshine complexes or with whole cells of non-conventional yeasts. Asymmetric hydrogenation was carried out using different approaches: hydrogenation of the tetra-substituted double bond of (E)-1-benzamido-3-ethoxy-3-oxo-1-phenylprop-1-en-2-yl ethyl oxalate 1 with Ir(I)–diphosphine complexes in the presence of TEA, hydrogenation of the carbonyl group

  通过过渡金属-二膦配合物或非常规酵母全细胞的不对称还原，获得了丰富的3-苯甲酰胺基-2-羟基-3-苯基丙酸乙酯（被保护的苯基异丝氨酸）（紫杉醇的手性侧链）。不对称氢化是使用不同的方法：（的四取代的双键的氢化ë）-1-苯甲酰氨基-3-乙氧基-3-氧代-1-苯基丙-1-烯-2-基草酸乙酯1与铱配（I）在TEA存在-diphosphine配合物，外消旋3-苯甲酰氨基-2-氧代-3-苯基丙的羰基的氢化2与钌（II）配合物-diphoshine在路易斯酸和最后一个的存在（E的两步酶促转化）-1-苯甲酰胺基-3-乙氧基-3-氧代-1-苯基丙-1-烯-2-基草酸乙酯1被带有细胞结合酯酶和脱氢酶的酵母全细胞催化。
• US5420337A
  申请人：——

  公开号：US5420337A

  公开（公告）日：1995-05-30
• US5602272A
  申请人：——

  公开号：US5602272A

  公开（公告）日：1997-02-11
• US5686298A
  申请人：——

  公开号：US5686298A

  公开（公告）日：1997-11-11