benzyl 2-[(1R,2R,4R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxyacetate | 148146-94-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: benzyl 2-[(1R,2R,4R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxyacetate
• CAS: 148146-94-5
• 化学式: C₅₂H₇₇NO₁₄
• 分子量: 940.182
• InChiKey: NJVLBGWAPTWMBD-LDKTYTPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  67
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  194
• 氢给体数：
  2
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  benzyl 2-[(1R,2R,4R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxyacetate 在 palladium on activated charcoal N-甲基吗啉 、 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.75h， 生成
  参考文献：
  名称：

  32-Ascomycinyloxyacetic Acid Derived Immunosuppressants. Independence of Immunophilin Binding and Immunosuppressive Potency

  摘要：

  The potent immunosuppressant ascomycin (1b) was selectively alkylated at the C-32 carbinol, thus providing esters and amides of 32-ascomycinyloxyacetic acid (4, AOAA). These compounds present structural variation at the FKBP/calcineurin interface. While the native carboxylic acid 4 shows no activity in vitro, esters and simple amides of 4 exhibit potent immunosuppression in the human MLR assay. Moreover, amides show inhibitory activity in the rat popliteal lymph node hyperplasia assay. Surprisingly, FKBP binding was weakened by several orders of magnitude when secondary hydrophobic aryl amides of 4 were tested, while maintaining potent immunosuppressive efficacy in vitro.

  DOI：

  10.1021/jm960066y
• 作为产物：
  描述：

  2-溴乙酸苄酯 在 sodium iodide 、 silver(l) oxide 作用下， 以 二氯甲烷 、 丙酮 、 乙腈 为溶剂， 反应 168.58h， 生成 benzyl 2-[(1R,2R,4R)-4-[(E)-2-[(1R,9S,12S,13R,14S,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1,14-dihydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-2,3,10,16-tetraoxo-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-en-12-yl]prop-1-enyl]-2-methoxycyclohexyl]oxyacetate
  参考文献：
  名称：

  32-Ascomycinyloxyacetic Acid Derived Immunosuppressants. Independence of Immunophilin Binding and Immunosuppressive Potency

  摘要：

  The potent immunosuppressant ascomycin (1b) was selectively alkylated at the C-32 carbinol, thus providing esters and amides of 32-ascomycinyloxyacetic acid (4, AOAA). These compounds present structural variation at the FKBP/calcineurin interface. While the native carboxylic acid 4 shows no activity in vitro, esters and simple amides of 4 exhibit potent immunosuppression in the human MLR assay. Moreover, amides show inhibitory activity in the rat popliteal lymph node hyperplasia assay. Surprisingly, FKBP binding was weakened by several orders of magnitude when secondary hydrophobic aryl amides of 4 were tested, while maintaining potent immunosuppressive efficacy in vitro.

  DOI：

  10.1021/jm960066y

文献信息

• 32-Ascomycinyloxyacetic Acid Derived Immunosuppressants. Independence of Immunophilin Binding and Immunosuppressive Potency
  作者：Rolf Wagner、Teresa A. Rhoades、Yat Sun Or、Benjamin C. Lane、Gin Hsieh、Karl W. Mollison、Jay R. Luly

  DOI：10.1021/jm960066y

  日期：1998.5.1

  The potent immunosuppressant ascomycin (1b) was selectively alkylated at the C-32 carbinol, thus providing esters and amides of 32-ascomycinyloxyacetic acid (4, AOAA). These compounds present structural variation at the FKBP/calcineurin interface. While the native carboxylic acid 4 shows no activity in vitro, esters and simple amides of 4 exhibit potent immunosuppression in the human MLR assay. Moreover, amides show inhibitory activity in the rat popliteal lymph node hyperplasia assay. Surprisingly, FKBP binding was weakened by several orders of magnitude when secondary hydrophobic aryl amides of 4 were tested, while maintaining potent immunosuppressive efficacy in vitro.