(2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid diethyl ester | 244008-58-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid diethyl ester
• 英文别名: (1R,2R,4S)-7-diethoxyphosphoryl-7-azabicyclo[2.2.1]heptan-2-ol
• CAS: 244008-58-0
• 化学式: C₁₀H₂₀NO₄P
• 分子量: 249.247
• InChiKey: RKODAGVZYBCURS-IVZWLZJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid diethyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 2-endo-hydroxy-7-azanorbornane
  参考文献：
  名称：

  Syntheses of New Phosphorus-Containing Azabicycloalkanes and Their Microbial Hydroxylation Using Beauveria bassiana

  摘要：

  Representative novel phosphorus-containing azabicyclic substrates have been synthesized and subsequently microbially hydroxylated in fair to good yields using the microorganism Beauveria bassiana. (7-Azabicyclo[2.2.1]hept-7-yl)phosphonic acid diethyl ester was hydroxylated at the unactivated methylene carbon to give (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid diethyl ester in 43% yield and 64% ee, while N-(diphenylphosphinoyl)-7-azabicyclo[2.2.1]heptane was similarly hydroxylated to give 2-endo-hydroxy-7-(diphenylphosphinoyl)-7-azabicyclo[2.2.1]- heptane in 35% yield and 20% ee. (7-Azabicyclo[2.2.1]hept-7-yl)phosphonic acid diphenyl ester yielded two distinct hydroxylated products: monohydroxylated (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid diphenyl ester in 7% yield and 7% ee and dihydroxylated (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid phenyl, p-hydroxyphenyl ester in 37% yield and 77% ee. HPLC studies indicated that the monohydroxylated metabolite is formed first during fermentation, and becomes a substrate for a second enzymatic hydroxylation at one of the aromatic rings with induced enantioselection, to give the dihydroxylated metabolite. All microbially hydroxylated metabolites were easily N-deproteded using TFA-CH2Cl2 (1:1). Thus, N-phosphinyl groups are good facilitators of hydroxylation reactions with B. bassiana and offer a new choice for an N-substituent when substrates are hydroxylated with this microorganism. By offering a new N-substituent, this work extends the general utility of B. bassiana as a preparatively useful unactivated methylene hydroxylated.

  DOI：

  10.1021/jo9904664
• 作为产物：
  描述：

  (trans-1,4-cyclohexanolyl)phosphoramidic acid diethyl ester 在 葡萄糖 、 Beauveria bassiana ATCC 7159 stage II liquid culture 、 corn steep liquor 、 potassium tert-butylate 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 174.0h， 生成 (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid diethyl ester
  参考文献：
  名称：

  Syntheses of New Phosphorus-Containing Azabicycloalkanes and Their Microbial Hydroxylation Using Beauveria bassiana

  摘要：

  Representative novel phosphorus-containing azabicyclic substrates have been synthesized and subsequently microbially hydroxylated in fair to good yields using the microorganism Beauveria bassiana. (7-Azabicyclo[2.2.1]hept-7-yl)phosphonic acid diethyl ester was hydroxylated at the unactivated methylene carbon to give (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid diethyl ester in 43% yield and 64% ee, while N-(diphenylphosphinoyl)-7-azabicyclo[2.2.1]heptane was similarly hydroxylated to give 2-endo-hydroxy-7-(diphenylphosphinoyl)-7-azabicyclo[2.2.1]- heptane in 35% yield and 20% ee. (7-Azabicyclo[2.2.1]hept-7-yl)phosphonic acid diphenyl ester yielded two distinct hydroxylated products: monohydroxylated (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid diphenyl ester in 7% yield and 7% ee and dihydroxylated (2-endo-hydroxy-7-azabicyclo[2.2.1]hept-7-yl)phosphonic acid phenyl, p-hydroxyphenyl ester in 37% yield and 77% ee. HPLC studies indicated that the monohydroxylated metabolite is formed first during fermentation, and becomes a substrate for a second enzymatic hydroxylation at one of the aromatic rings with induced enantioselection, to give the dihydroxylated metabolite. All microbially hydroxylated metabolites were easily N-deproteded using TFA-CH2Cl2 (1:1). Thus, N-phosphinyl groups are good facilitators of hydroxylation reactions with B. bassiana and offer a new choice for an N-substituent when substrates are hydroxylated with this microorganism. By offering a new N-substituent, this work extends the general utility of B. bassiana as a preparatively useful unactivated methylene hydroxylated.

  DOI：

  10.1021/jo9904664