methyl 4-amino-4-deoxy-5,10-methylene-5,6,7,8-tetrahydro-8,10-dideazapteroate | 103004-00-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl 4-amino-4-deoxy-5,10-methylene-5,6,7,8-tetrahydro-8,10-dideazapteroate
• CAS: 103004-00-8
• 化学式: C₁₈H₂₁N₅O₂
• 分子量: 339.397
• InChiKey: CLVAODMCZKMXLB-UHFFFAOYSA-N

物化性质

• 沸点：
  628.6±65.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.74
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  107.36
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 4-amino-4-deoxy-5,10-methylene-5,6,7,8-tetrahydro-8,10-dideazapteroate 在 sodium hydroxide 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 乙二醇甲醚 、 水 为溶剂， 反应 41.5h， 生成 (2S)-diethyl 2-(4-(1,3-diamino-5,6,6a,7,8,9-hexahydropyrimido[5,4-e]indolizin-8-yl)benzamido)pentanedioate
  参考文献：
  名称：

  Synthesis and antifolate properties of 5,10-methylenetetrahydro-8,10-dideazaminopterin

  摘要：

  The synthesis of the 5,10-methylene analogue of 5,6,7,8-tetrahydro-8,10-dideazaminopterin, a potential dual inhibitor of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzymes, is described. The dimethyl ester of 10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid was converted to the tetrahydro derivative by hydrogenation. Thermally induced cyclization of the 10-carbomethoxy and the 5-NH groups afforded the 5,10-carbonyl analogue. Reduction of the lactam with borane readily yielded the key 5,10-methylene-4-amino-4-deoxy-8,10-dideazatetrahydropteroic acid methyl ester. Saponification of the benzoate ester and coupling with L-glutamate concluded the synthesis. The title compound was a modest inhibitor of growth in folate-dependent bacteria. Streptococcus faecium and Lactobacillus casei, but inhibition of DHFR or TS derived from L. casei was poor. The compound was also a weak inhibitor of DHFR derived from L1210 murine leukemia and was a weak inhibitor of L1210 growth in culture.

  DOI：

  10.1021/jm00159a039
• 作为产物：
  描述：

  methyl 4-amino-4-deoxy-5,10-carbonyl-5,6,7,8-tetrahydro-8,10-dideazapteroate 在 盐酸 、 硼烷 作用下， 生成 methyl 4-amino-4-deoxy-5,10-methylene-5,6,7,8-tetrahydro-8,10-dideazapteroate
  参考文献：
  名称：

  Synthesis and antifolate properties of 5,10-methylenetetrahydro-8,10-dideazaminopterin

  摘要：

  The synthesis of the 5,10-methylene analogue of 5,6,7,8-tetrahydro-8,10-dideazaminopterin, a potential dual inhibitor of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) enzymes, is described. The dimethyl ester of 10-carboxy-4-amino-4-deoxy-8,10-dideazapteroic acid was converted to the tetrahydro derivative by hydrogenation. Thermally induced cyclization of the 10-carbomethoxy and the 5-NH groups afforded the 5,10-carbonyl analogue. Reduction of the lactam with borane readily yielded the key 5,10-methylene-4-amino-4-deoxy-8,10-dideazatetrahydropteroic acid methyl ester. Saponification of the benzoate ester and coupling with L-glutamate concluded the synthesis. The title compound was a modest inhibitor of growth in folate-dependent bacteria. Streptococcus faecium and Lactobacillus casei, but inhibition of DHFR or TS derived from L. casei was poor. The compound was also a weak inhibitor of DHFR derived from L1210 murine leukemia and was a weak inhibitor of L1210 growth in culture.

  DOI：

  10.1021/jm00159a039