(-)-pinanediol (1S)-(1-aminoethyl)-1-boronate hydrochloride | 1265111-23-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (-)-pinanediol (1S)-(1-aminoethyl)-1-boronate hydrochloride
• 英文别名: (S)-BoroAla-(-)-Pinanediol-HCl；(1S)-1-[(1R,2R,6S,8R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethanamine;hydrochloride
• CAS: 1265111-23-6
• 化学式: C₁₂H₂₂BNO₂*ClH
• 分子量: 259.584
• InChiKey: UTMUMWPHEOQEQA-IMOBDCPJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.02
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  44.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (-)-pinanediol (1S)-(1-aminoethyl)-1-boronate hydrochloride 在 盐酸 、 苯硼酸 作用下， 以 乙醚 、 水 为溶剂， 反应 1.0h， 生成 (1S)-(1-aminoethyl)-1-boronate hydrochloride
  参考文献：
  名称：

  Characterization of d-boroAla as a Novel Broad-Spectrum Antibacterial Agent Targeting d-Ala-d-Ala Ligase

  摘要：

  d‐boroAla was previously characterized as an inhibitor of bacterial alanine racemase and d‐Ala‐d‐Ala ligase enzymes (Biochemistry, 28, 1989, 3541). In this study, d‐boroAla was identified and characterized as an antibacterial agent. d‐boroAla has activity against both Gram‐positive and Gram‐negative organisms, with minimal inhibitory concentrations down to 8 μg / mL. A structure–function study on the alkyl side chain (NH2‐CHR‐B(OR’)2) revealed that d‐boroAla is the most effective agent in a series including boroGly, d‐boroHomoAla, and d‐boroVal. l‐boroAla was much less active, and N‐acetylation completely abolished activity. An LC‐MS / MS assay was used to demonstrate that d‐boroAla exerts its antibacterial activity by inhibition of d‐Ala‐d‐Ala ligase. d‐boroAla is bactericidal at 1× minimal inhibitory concentration against Staphylococcus aureus and Bacillus subtilis, which each encode one copy of d‐Ala‐d‐Ala ligase, and at 4× minimal inhibitory concentration against Escherichia coli and Salmonella enterica serovar Typhimurium, which each encode two copies of d‐Ala‐d‐Ala ligase. d‐boroAla demonstrated a frequency of resistance of 8 × 10−8 at 4× minimal inhibitory concentration in S. aureus. These results demonstrate that d‐boroAla has promising antibacterial activity and could serve as the lead agent in a new class of d‐Ala‐d‐Ala ligase targeted antibacterial agents. This study also demonstrates d‐boroAla as a possible probe for d‐Ala‐d‐Ala ligase function.

  DOI：

  10.1111/j.1747-0285.2011.01210.x
• 作为产物：
  描述：

  1,1,1-trimethyl-N-((S)-1-((3aR,4R,6R,7aS)-3a,5,5-trimethylhexahydro-4,6-methanobenzo[d][1,3,2]dioxaborol-2-yl)ethyl)-N-(trimethylsilyl)silanamine 在 盐酸 作用下， 以 乙醚 为溶剂， 以95%的产率得到(-)-pinanediol (1S)-(1-aminoethyl)-1-boronate hydrochloride
  参考文献：
  名称：

  Structure Guided Development of Potent Reversibly Binding Penicillin Binding Protein Inhibitors

  摘要：

  Following from the evaluation of different types of electrophiles, combined modeling and crystallographic analyses are used to generate potent boronic acid based inhibitors of a penicillin binding protein. The results suggest that a structurally informed approach to penicillin binding protein inhibition will be useful for the development of both improved reversibly binding inhibitors, including boronic acids, and acylating inhibitors, such as beta-lactams.

  DOI：

  10.1021/ml100260x

文献信息

• Characterization of d-boroAla as a Novel Broad-Spectrum Antibacterial Agent Targeting d-Ala-d-Ala Ligase
  作者：Sandeep Putty、Aman Rai、Darshan Jamindar、Paul Pagano、Cheryl L. Quinn、Takehiko Mima、Herbert P. Schweizer、William G. Gutheil

  DOI：10.1111/j.1747-0285.2011.01210.x

  日期：2011.11

  d‐boroAla was previously characterized as an inhibitor of bacterial alanine racemase and d‐Ala‐d‐Ala ligase enzymes (Biochemistry, 28, 1989, 3541). In this study, d‐boroAla was identified and characterized as an antibacterial agent. d‐boroAla has activity against both Gram‐positive and Gram‐negative organisms, with minimal inhibitory concentrations down to 8 μg / mL. A structure–function study on the alkyl side chain (NH2‐CHR‐B(OR’)2) revealed that d‐boroAla is the most effective agent in a series including boroGly, d‐boroHomoAla, and d‐boroVal. l‐boroAla was much less active, and N‐acetylation completely abolished activity. An LC‐MS / MS assay was used to demonstrate that d‐boroAla exerts its antibacterial activity by inhibition of d‐Ala‐d‐Ala ligase. d‐boroAla is bactericidal at 1× minimal inhibitory concentration against Staphylococcus aureus and Bacillus subtilis, which each encode one copy of d‐Ala‐d‐Ala ligase, and at 4× minimal inhibitory concentration against Escherichia coli and Salmonella enterica serovar Typhimurium, which each encode two copies of d‐Ala‐d‐Ala ligase. d‐boroAla demonstrated a frequency of resistance of 8 × 10−8 at 4× minimal inhibitory concentration in S. aureus. These results demonstrate that d‐boroAla has promising antibacterial activity and could serve as the lead agent in a new class of d‐Ala‐d‐Ala ligase targeted antibacterial agents. This study also demonstrates d‐boroAla as a possible probe for d‐Ala‐d‐Ala ligase function.
• Structure Guided Development of Potent Reversibly Binding Penicillin Binding Protein Inhibitors
  作者：Esther C. Y. Woon、Astrid Zervosen、Eric Sauvage、Katie J. Simmons、Matej Živec、Steven R. Inglis、Colin W. G. Fishwick、Stanislav Gobec、Paulette Charlier、André Luxen、Christopher J. Schofield

  DOI：10.1021/ml100260x

  日期：2011.3.10

  Following from the evaluation of different types of electrophiles, combined modeling and crystallographic analyses are used to generate potent boronic acid based inhibitors of a penicillin binding protein. The results suggest that a structurally informed approach to penicillin binding protein inhibition will be useful for the development of both improved reversibly binding inhibitors, including boronic acids, and acylating inhibitors, such as beta-lactams.