{4-[2,4-Dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxy-pentylamino)-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-butyl}-phosphonic acid dibenzyl ester | 474644-29-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: {4-[2,4-Dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxy-pentylamino)-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-butyl}-phosphonic acid dibenzyl ester
• 英文别名: 5-bis(phenylmethoxy)phosphoryl-N-[2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1H-pyrimidin-5-yl]pentanamide
• CAS: 474644-29-6
• 化学式: C₂₈H₃₇N₄O₁₀P
• 分子量: 620.596
• InChiKey: HCBBXNIVJFOZSD-FBLLAGFSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  43
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  216
• 氢给体数：
  8
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  {4-[2,4-Dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxy-pentylamino)-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-butyl}-phosphonic acid dibenzyl ester 在 palladium dihydroxide 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 12.0h， 以0.3 g的产率得到[5-[[2,4-dioxo-6-[[(2S,3S,4R)-2,3,4,5-tetrahydroxypentyl]amino]-1H-pyrimidin-5-yl]amino]-5-oxopentyl]phosphonic acid
  参考文献：
  名称：

  Incorporation of an Amide into 5-Phosphonoalkyl-6-d-ribitylaminopyrimidinedione Lumazine Synthase Inhibitors Results in an Unexpected Reversal of Selectivity for Riboflavin Synthase vs Lumazine Synthase

  摘要：

  Several analogues of a hypothetical intermediate in the reaction catalyzed by lumazine synthase were synthesized and tested as inhibitors of both Bacillus subtilis lumazine synthase and Escherichia coli riboflavin synthase. The new compounds were designed by replacement of a two-carbon fragment of several 5-phosphonoalkyl-6-D-ribitylaminopyrimidinedione lumazine synthase inhibitors with an amide linkage that was envisioned as an analogue of a Schiff base moiety of a hypothetical intermediate in the enzyme-catalyzed reaction. The incorporation of the amide group led to an unexpected reversal in selectivity for inhibition of lumazine synthase vs riboflavin synthase. Whereas the parent 5-phosphonoalkyl-6-D-ribitylaminopyrimidinediones were lumazine synthase inhibitors and did not inhibit riboflavin synthase, the amide-containing derivatives inhibited riboflavin synthase and were only very weak or inactive as lumazine synthase inhibitors. Molecular modeling of inhibitor-lumazine synthase complexes did not reveal a structural basis for these unexpected findings. However, molecular modeling of one of the inhibitors with E. coli riboflavin synthase demonstrated that the active site of the enzyme could readily accommodate two ligand molecules.

  DOI：

  10.1021/jo020144r
• 作为产物：
  描述：

  亚磷酸二苄酯 在 lithium hydroxide 、 草酰氯 、 sodium hydride 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 40.25h， 生成 {4-[2,4-Dioxo-6-((2S,3S,4R)-2,3,4,5-tetrahydroxy-pentylamino)-1,2,3,4-tetrahydro-pyrimidin-5-ylcarbamoyl]-butyl}-phosphonic acid dibenzyl ester
  参考文献：
  名称：

  Incorporation of an Amide into 5-Phosphonoalkyl-6-d-ribitylaminopyrimidinedione Lumazine Synthase Inhibitors Results in an Unexpected Reversal of Selectivity for Riboflavin Synthase vs Lumazine Synthase

  摘要：

  Several analogues of a hypothetical intermediate in the reaction catalyzed by lumazine synthase were synthesized and tested as inhibitors of both Bacillus subtilis lumazine synthase and Escherichia coli riboflavin synthase. The new compounds were designed by replacement of a two-carbon fragment of several 5-phosphonoalkyl-6-D-ribitylaminopyrimidinedione lumazine synthase inhibitors with an amide linkage that was envisioned as an analogue of a Schiff base moiety of a hypothetical intermediate in the enzyme-catalyzed reaction. The incorporation of the amide group led to an unexpected reversal in selectivity for inhibition of lumazine synthase vs riboflavin synthase. Whereas the parent 5-phosphonoalkyl-6-D-ribitylaminopyrimidinediones were lumazine synthase inhibitors and did not inhibit riboflavin synthase, the amide-containing derivatives inhibited riboflavin synthase and were only very weak or inactive as lumazine synthase inhibitors. Molecular modeling of inhibitor-lumazine synthase complexes did not reveal a structural basis for these unexpected findings. However, molecular modeling of one of the inhibitors with E. coli riboflavin synthase demonstrated that the active site of the enzyme could readily accommodate two ligand molecules.

  DOI：

  10.1021/jo020144r

文献信息

• Incorporation of an Amide into 5-Phosphonoalkyl-6-<scp>d</scp>-ribitylaminopyrimidinedione Lumazine Synthase Inhibitors Results in an Unexpected Reversal of Selectivity for Riboflavin Synthase vs Lumazine Synthase
  作者：Mark Cushman、Donglai Yang、Jeffrey T. Mihalic、Jinhua Chen、Stefan Gerhardt、Robert Huber、Markus Fischer、Klaus Kis、Adelbert Bacher

  DOI：10.1021/jo020144r

  日期：2002.10.1

  Several analogues of a hypothetical intermediate in the reaction catalyzed by lumazine synthase were synthesized and tested as inhibitors of both Bacillus subtilis lumazine synthase and Escherichia coli riboflavin synthase. The new compounds were designed by replacement of a two-carbon fragment of several 5-phosphonoalkyl-6-D-ribitylaminopyrimidinedione lumazine synthase inhibitors with an amide linkage that was envisioned as an analogue of a Schiff base moiety of a hypothetical intermediate in the enzyme-catalyzed reaction. The incorporation of the amide group led to an unexpected reversal in selectivity for inhibition of lumazine synthase vs riboflavin synthase. Whereas the parent 5-phosphonoalkyl-6-D-ribitylaminopyrimidinediones were lumazine synthase inhibitors and did not inhibit riboflavin synthase, the amide-containing derivatives inhibited riboflavin synthase and were only very weak or inactive as lumazine synthase inhibitors. Molecular modeling of inhibitor-lumazine synthase complexes did not reveal a structural basis for these unexpected findings. However, molecular modeling of one of the inhibitors with E. coli riboflavin synthase demonstrated that the active site of the enzyme could readily accommodate two ligand molecules.