Terfenadine aldehyde metabolite | 142154-45-8

• 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: Terfenadine aldehyde metabolite
• 英文别名: 2-[4-[1-hydroxy-4-[4-[hydroxy(diphenyl)methyl]piperidin-1-yl]butyl]phenyl]-2-methylpropanal
• CAS: 142154-45-8
• 化学式: C₃₂H₃₉NO₃
• 分子量: 485.667
• InChiKey: SMYNOPZGCCLROM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  60.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Terfenadine aldehyde metabolite 在 氧气-18O2 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 48.0h， 生成
  参考文献：
  名称：

  Biooxidation of methyl group: Part 2. Evidences for the involvement of cytochromes P450 in microbial multistep oxidation of terfenadine

  摘要：

  The actinomycete Streptomyces platensis grown in culture medium containing soybean peptones can transform terfenadine, an antihistamine drug, into its active metabolite fexofenadine. The microbial oxidation of methyl group of terfenadine into carboxylic acid could be an alternative to chemical ways to produce fexofenadine. This bioconversion requires three oxidation steps: a hydroxylation of one methyl group followed by the oxidation of the corresponding alcohol into the aldehyde and finally its oxidation into the carboxylic acid. The oxidation reaction of each step has been studied. Terfenadine and intermediates incubated with whole cells were not oxidized under argon whereas their biotransformation under O-18(2)-enriched atmosphere gave labeled fexofenadine. P450 inhibitors, such as clotrimazole or fluconazole, inhibited oxidation activity of each step. While the two last steps could be catalyzed by dehydrogenases or oxidases, this study strongly demonstrates the role of at least one, or possibly several cytochromes P450, in the oxidation of terfenadine into fexofenadine by S. platensis cells. To our knowledge, this is one of the few examples of involvement of P450s in such three steps oxidation of a xenobiotic. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2010.07.017
• 作为产物：
  描述：

  2-(4-(1-hydroxy-4-(4-(hydroxydiphenylmethyl)-1-piperidinyl)-butyl)-phenyl)-2-methyl-propanol 在 N-氯代丁二酰亚胺 、 2,2,6,6-四甲基哌啶氧化物 、 四丁基氯化铵 、 碳酸氢钠 、 potassium carbonate 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 3.0h， 以45%的产率得到Terfenadine aldehyde metabolite
  参考文献：
  名称：

  Biooxidation of methyl group: Part 2. Evidences for the involvement of cytochromes P450 in microbial multistep oxidation of terfenadine

  摘要：

  The actinomycete Streptomyces platensis grown in culture medium containing soybean peptones can transform terfenadine, an antihistamine drug, into its active metabolite fexofenadine. The microbial oxidation of methyl group of terfenadine into carboxylic acid could be an alternative to chemical ways to produce fexofenadine. This bioconversion requires three oxidation steps: a hydroxylation of one methyl group followed by the oxidation of the corresponding alcohol into the aldehyde and finally its oxidation into the carboxylic acid. The oxidation reaction of each step has been studied. Terfenadine and intermediates incubated with whole cells were not oxidized under argon whereas their biotransformation under O-18(2)-enriched atmosphere gave labeled fexofenadine. P450 inhibitors, such as clotrimazole or fluconazole, inhibited oxidation activity of each step. While the two last steps could be catalyzed by dehydrogenases or oxidases, this study strongly demonstrates the role of at least one, or possibly several cytochromes P450, in the oxidation of terfenadine into fexofenadine by S. platensis cells. To our knowledge, this is one of the few examples of involvement of P450s in such three steps oxidation of a xenobiotic. (C) 2010 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molcatb.2010.07.017

文献信息

• Biooxidation of methyl group: Part 2. Evidences for the involvement of cytochromes P450 in microbial multistep oxidation of terfenadine
  作者：Amane El Ouarradi、Murielle Lombard、Didier Buisson

  DOI：10.1016/j.molcatb.2010.07.017

  日期：2010.12

  The actinomycete Streptomyces platensis grown in culture medium containing soybean peptones can transform terfenadine, an antihistamine drug, into its active metabolite fexofenadine. The microbial oxidation of methyl group of terfenadine into carboxylic acid could be an alternative to chemical ways to produce fexofenadine. This bioconversion requires three oxidation steps: a hydroxylation of one methyl group followed by the oxidation of the corresponding alcohol into the aldehyde and finally its oxidation into the carboxylic acid. The oxidation reaction of each step has been studied. Terfenadine and intermediates incubated with whole cells were not oxidized under argon whereas their biotransformation under O-18(2)-enriched atmosphere gave labeled fexofenadine. P450 inhibitors, such as clotrimazole or fluconazole, inhibited oxidation activity of each step. While the two last steps could be catalyzed by dehydrogenases or oxidases, this study strongly demonstrates the role of at least one, or possibly several cytochromes P450, in the oxidation of terfenadine into fexofenadine by S. platensis cells. To our knowledge, this is one of the few examples of involvement of P450s in such three steps oxidation of a xenobiotic. (C) 2010 Elsevier B.V. All rights reserved.