methyl (S)-4-<(benzyloxycarbonyl)amino>-2-oxopentanoate | 215608-33-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: methyl (S)-4-<(benzyloxycarbonyl)amino>-2-oxopentanoate
• 英文别名: methyl (4S)-2-oxo-4-(phenylmethoxycarbonylamino)pentanoate
• CAS: 215608-33-6
• 化学式: C₁₄H₁₇NO₅
• 分子量: 279.293
• InChiKey: ROIQOOMPVKERCK-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (S)-4-<(benzyloxycarbonyl)amino>-2-oxopentanoate 在 1,4-dihydronicotinamide adenine dinucleotide 、 lactate dehydrogenase from Bacillus Stearothermophilus (BS-LDH) 、 sodium formate 、 磷脂酶B 作用下， 生成 (2S,4S)-4-Benzyloxycarbonylamino-2-hydroxy-pentanoic acid
  参考文献：
  名称：

  Chemoenzymatic Synthesis of 4-Amino-2-hydroxy Acids:  A Comparison of Mutant and Wild-Type Oxidoreductases

  摘要：

  We describe a new chemoenzymatic synthesis of enantiopure 4-amino-2-hydroxy acids using two biotransformations in a single-pot process in aqueous medium. These compounds are valuable as gamma-turn mimics for investigations into the secondary structure of peptides. The enzyme substrates are a series of carbobenzyloxy (CBZ)-protected 4-amino-2-keto esters, prepared efficiently from the L-amino acids, alanine, leucine, phenylalanine, and valine. First, the alpha-amino acids were converted to the corresponding beta-amino acids in a simple five-step procedure. A further one-carbon homologation via ozonolysis of the corresponding beta-keto cyanophosphoranes gave the required alpha-keto esters in good yield. The enzyme catalyzed hydrolyses of all the alpha-keto esters to the corresponding alpha-keto acids proceeded smoothly with the lipase from Candida rugosa. Using the same reaction pot, it was found that wild-type lactate dehydrogenases from either Bacillus stearothermophilus (BS-LDH) or Staphylococcus epidermidis (SE-LDH) could be used to specifically reduce the ketone of the alanine-derived alpha-keto acid 2, giving the (S)- and (R)-2-hydroxy acids, respectively, in good yields. However, the more bulky alpha-keto acids 3, 4, and 5 (derived from valine, leucine, and phenylalanine) were not substrates for these enzymes. In contrast, the genetically engineered H205Q mutant of D-hydroxyisocaproate dehydrogenase proved to be an ideal catalyst for the reduction of all the alpha-keto acids 2-5, giving excellent yields of the CBZ-protected (2R,4S)-4-amino-2-hydroxy acids as single diastereomers. This genetically engineered oxidoreductase has great potential value in synthesis due to its broad substrate specificity and high catalytic activity. For example, reduction of 1 mmol of N-protected (S)-4-amino-2-oxopentanoic acid 2 took just 4 h with the H205Q mutant giving, after esterification, the (R)-2-alcohol 25 in 85% yield, whereas with SE-LDH the reaction required 4 days to give a 67% yield of 25.

  DOI：

  10.1021/jo980821a
• 作为产物：
  描述：

  (S)-3-Cbz-氨基丁酸 在 4-二甲氨基吡啶 、 臭氧 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 16.0h， 生成 methyl (S)-4-<(benzyloxycarbonyl)amino>-2-oxopentanoate
  参考文献：
  名称：

  Chemoenzymatic Synthesis of 4-Amino-2-hydroxy Acids:  A Comparison of Mutant and Wild-Type Oxidoreductases

  摘要：

  We describe a new chemoenzymatic synthesis of enantiopure 4-amino-2-hydroxy acids using two biotransformations in a single-pot process in aqueous medium. These compounds are valuable as gamma-turn mimics for investigations into the secondary structure of peptides. The enzyme substrates are a series of carbobenzyloxy (CBZ)-protected 4-amino-2-keto esters, prepared efficiently from the L-amino acids, alanine, leucine, phenylalanine, and valine. First, the alpha-amino acids were converted to the corresponding beta-amino acids in a simple five-step procedure. A further one-carbon homologation via ozonolysis of the corresponding beta-keto cyanophosphoranes gave the required alpha-keto esters in good yield. The enzyme catalyzed hydrolyses of all the alpha-keto esters to the corresponding alpha-keto acids proceeded smoothly with the lipase from Candida rugosa. Using the same reaction pot, it was found that wild-type lactate dehydrogenases from either Bacillus stearothermophilus (BS-LDH) or Staphylococcus epidermidis (SE-LDH) could be used to specifically reduce the ketone of the alanine-derived alpha-keto acid 2, giving the (S)- and (R)-2-hydroxy acids, respectively, in good yields. However, the more bulky alpha-keto acids 3, 4, and 5 (derived from valine, leucine, and phenylalanine) were not substrates for these enzymes. In contrast, the genetically engineered H205Q mutant of D-hydroxyisocaproate dehydrogenase proved to be an ideal catalyst for the reduction of all the alpha-keto acids 2-5, giving excellent yields of the CBZ-protected (2R,4S)-4-amino-2-hydroxy acids as single diastereomers. This genetically engineered oxidoreductase has great potential value in synthesis due to its broad substrate specificity and high catalytic activity. For example, reduction of 1 mmol of N-protected (S)-4-amino-2-oxopentanoic acid 2 took just 4 h with the H205Q mutant giving, after esterification, the (R)-2-alcohol 25 in 85% yield, whereas with SE-LDH the reaction required 4 days to give a 67% yield of 25.

  DOI：

  10.1021/jo980821a

文献信息

• Chemoenzymatic Synthesis of 4-Amino-2-hydroxy Acids:  A Comparison of Mutant and Wild-Type Oxidoreductases
  作者：Andrew Sutherland、Christine L. Willis

  DOI：10.1021/jo980821a

  日期：1998.10.1

  We describe a new chemoenzymatic synthesis of enantiopure 4-amino-2-hydroxy acids using two biotransformations in a single-pot process in aqueous medium. These compounds are valuable as gamma-turn mimics for investigations into the secondary structure of peptides. The enzyme substrates are a series of carbobenzyloxy (CBZ)-protected 4-amino-2-keto esters, prepared efficiently from the L-amino acids, alanine, leucine, phenylalanine, and valine. First, the alpha-amino acids were converted to the corresponding beta-amino acids in a simple five-step procedure. A further one-carbon homologation via ozonolysis of the corresponding beta-keto cyanophosphoranes gave the required alpha-keto esters in good yield. The enzyme catalyzed hydrolyses of all the alpha-keto esters to the corresponding alpha-keto acids proceeded smoothly with the lipase from Candida rugosa. Using the same reaction pot, it was found that wild-type lactate dehydrogenases from either Bacillus stearothermophilus (BS-LDH) or Staphylococcus epidermidis (SE-LDH) could be used to specifically reduce the ketone of the alanine-derived alpha-keto acid 2, giving the (S)- and (R)-2-hydroxy acids, respectively, in good yields. However, the more bulky alpha-keto acids 3, 4, and 5 (derived from valine, leucine, and phenylalanine) were not substrates for these enzymes. In contrast, the genetically engineered H205Q mutant of D-hydroxyisocaproate dehydrogenase proved to be an ideal catalyst for the reduction of all the alpha-keto acids 2-5, giving excellent yields of the CBZ-protected (2R,4S)-4-amino-2-hydroxy acids as single diastereomers. This genetically engineered oxidoreductase has great potential value in synthesis due to its broad substrate specificity and high catalytic activity. For example, reduction of 1 mmol of N-protected (S)-4-amino-2-oxopentanoic acid 2 took just 4 h with the H205Q mutant giving, after esterification, the (R)-2-alcohol 25 in 85% yield, whereas with SE-LDH the reaction required 4 days to give a 67% yield of 25.