(3S,6S,7R)-3-((benzyloxy)methyl)-7-((tert-butyldiphenylsilyloxy)methyl)-6-hydroxy-4-methyl-1,4-diazepan-2-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,6S,7R)-3-((benzyloxy)methyl)-7-((tert-butyldiphenylsilyloxy)methyl)-6-hydroxy-4-methyl-1,4-diazepan-2-one
• 英文别名: (3S,6S,7R)-7-[[tert-butyl(diphenyl)silyl]oxymethyl]-6-hydroxy-4-methyl-3-(phenylmethoxymethyl)-1,4-diazepan-2-one
• 化学式: C₃₁H₄₀N₂O₄Si
• 分子量: 532.755
• InChiKey: ITIYZSUVDCFMIC-ULNSLHSMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  71
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,6S,7R)-3-((benzyloxy)methyl)-7-((tert-butyldiphenylsilyloxy)methyl)-6-hydroxy-4-methyl-1,4-diazepan-2-one 在 4-二甲氨基吡啶 、 氢气 、 钯 、 溶剂黄146 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 40.0h， 生成 (3S,6S,7R)-3-hydroxymethyl-7-tertbutyldiphenylsilyloxymethyl-4-N-methyl-6-palmitoyloxy-1,4-diazepan-2-one
  参考文献：
  名称：

  Synthesis and biological evaluation of a diazepanone-based library of liposidomycins analogs as MraY inhibitors

  摘要：

  New inhibitors of the bacterial tranferase MraY are described. A scaffold strategy based on the diazepanone central core of liposidomycins, natural inhibitors of MraY has been developed. It involves the introduction of key structural fragments required for biological activity on enantiopure diazepanones by reductive amination, esterification and glycosylation. Biological evaluation of these compounds on MraY enzyme revealed interesting inhibitory activity for compounds displaying three fragments on the scaffold: a palmitoyl chain, an aminoribose part and an alkyluracil moiety. The inhibitors were also evaluated on MurG enzyme. The best compounds resulted in inhibition with IC50 values in the 100 mu M range for one or the other enzyme. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.02.006
• 作为产物：
  描述：

  (2S)-2-[[(2S,3R)-3-amino-4-[tert-butyl(diphenyl)silyl]oxy-2-hydroxybutyl]-methylamino]-3-phenylmethoxypropanoic acid 在 1-羟基苯并三唑 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以30%的产率得到(3S,6S,7R)-3-((benzyloxy)methyl)-7-((tert-butyldiphenylsilyloxy)methyl)-6-hydroxy-4-methyl-1,4-diazepan-2-one
  参考文献：
  名称：

  高效合成多官能对映体纯二氮杂酮骨架

  摘要：

  描述了从l-丝氨酸衍生物和叠氮环氧化物容易地从l-抗坏血酸或d-异抗坏血酸获得的多官能化对映体纯的1，4-二氮杂-3-酮骨架的合成，其允许在手性中心获得各种构型。关键步骤是丝氨酸的胺向环氧化物的亲核打开，然后进行内酯化-内酰胺化序列。

  DOI：

  10.1016/j.tetlet.2007.09.098

文献信息

• Synthetic studies towards diazepanone scaffolds
  作者：Olivier Monasson、Maryon Ginisty、Janez Mravljak、Gildas Bertho、Christine Gravier-Pelletier、Yves Le Merrer

  DOI：10.1016/j.tetasy.2009.09.022

  日期：2009.10

  The synthesis of new enantiopure polyfunctionalised diazepanone scaffolds is described. The key steps involve the opening of an azido-epoxide C4 building block derived from L-ascorbic or D-isoascorbic acid by a L-serine derivative followed by a lactonisation-lactamisation two-step sequence. (C) 2009 Elsevier Ltd. All rights reserved.
• Efficient synthesis of polyfunctionalised enantiopure diazepanone scaffolds
  作者：Olivier Monasson、Maryon Ginisty、Gildas Bertho、Christine Gravier-Pelletier、Yves Le Merrer

  DOI：10.1016/j.tetlet.2007.09.098

  日期：2007.11

  The synthesis of polyfunctionalised enantiopure 1,4-diazepan-3-one scaffolds from l-serine derivatives and azidoepoxides readily available from either l-ascorbic or d-isoascorbic acid, allowing access to various configurations at chiral centres, is described. The key steps are the nucleophilic opening of the epoxide by the amine of serine followed by a lactonisation–lactamisation sequence.

  描述了从l-丝氨酸衍生物和叠氮环氧化物容易地从l-抗坏血酸或d-异抗坏血酸获得的多官能化对映体纯的1，4-二氮杂-3-酮骨架的合成，其允许在手性中心获得各种构型。关键步骤是丝氨酸的胺向环氧化物的亲核打开，然后进行内酯化-内酰胺化序列。
• Synthesis and biological evaluation of a diazepanone-based library of liposidomycins analogs as MraY inhibitors
  作者：Janez Mravljak、Olivier Monasson、Bayan Al-Dabbagh、Muriel Crouvoisier、Ahmed Bouhss、Christine Gravier-Pelletier、Yves Le Merrer

  DOI：10.1016/j.ejmech.2011.02.006

  日期：2011.5

  New inhibitors of the bacterial tranferase MraY are described. A scaffold strategy based on the diazepanone central core of liposidomycins, natural inhibitors of MraY has been developed. It involves the introduction of key structural fragments required for biological activity on enantiopure diazepanones by reductive amination, esterification and glycosylation. Biological evaluation of these compounds on MraY enzyme revealed interesting inhibitory activity for compounds displaying three fragments on the scaffold: a palmitoyl chain, an aminoribose part and an alkyluracil moiety. The inhibitors were also evaluated on MurG enzyme. The best compounds resulted in inhibition with IC50 values in the 100 mu M range for one or the other enzyme. (C) 2011 Elsevier Masson SAS. All rights reserved.