[(2S,3R,4S,6R)-2-[[(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-6-[(2R,4R,5S,6S)-5-acetyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-15-(1-benzhydrylazetidin-3-yl)-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-8-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] acetate | 893565-91-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [(2S,3R,4S,6R)-2-[[(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-6-[(2R,4R,5S,6S)-5-acetyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-15-(1-benzhydrylazetidin-3-yl)-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-8-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] acetate
• CAS: 893565-91-8
• 化学式: C₅₉H₈₇N₃O₁₅
• 分子量: 1078.35
• InChiKey: UVVXMLLBXDKOOI-IOIQLGRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.6
• 重原子数：
  77
• 可旋转键数：
  16
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  187
• 氢给体数：
  0
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  [(2S,3R,4S,6R)-2-[[(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-6-[(2R,4R,5S,6S)-5-acetyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-15-(1-benzhydrylazetidin-3-yl)-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-8-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] acetate 在 盐酸 、 甲醇 、 N-氯代丁二酰亚胺 、 二甲基硫 、 20 % Pd(OH)2/C 、 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 乙腈 为溶剂， 反应 42.0h， 生成 3-descladinosyl-11,12-dideoxy-6-O-methyl-3-oxo-12,11-(oxycarbonyl-(1-((3-hydroxy-[1,5]naphthyridin-4-yl)-methyl)-azetidin-3-yl)-imino)-erythromycin A
  参考文献：
  名称：

  Process Development of a Novel Azetidinyl Ketolide Antibiotic

  摘要：

  Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.

  DOI：

  10.1021/op300064b
• 作为产物：
  描述：

  克拉霉素 在 4-二甲氨基吡啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 50.0h， 生成 [(2S,3R,4S,6R)-2-[[(1S,2R,5R,6S,7S,8R,9R,11R,13R,14R)-6-[(2R,4R,5S,6S)-5-acetyloxy-4-methoxy-4,6-dimethyloxan-2-yl]oxy-15-(1-benzhydrylazetidin-3-yl)-2-ethyl-9-methoxy-1,5,7,9,11,13-hexamethyl-4,12,16-trioxo-3,17-dioxa-15-azabicyclo[12.3.0]heptadecan-8-yl]oxy]-4-(dimethylamino)-6-methyloxan-3-yl] acetate
  参考文献：
  名称：

  Process Development of a Novel Azetidinyl Ketolide Antibiotic

  摘要：

  Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.

  DOI：

  10.1021/op300064b