(alphaR,3aS,4S,6S,7aR)-六氢-alpha,3a,5,5-四甲基-4,6-甲桥-1,3,2-苯并二氧硼烷-2-甲胺 | 497165-15-8

• 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
• 中文名称: (alphaR,3aS,4S,6S,7aR)-六氢-alpha,3a,5,5-四甲基-4,6-甲桥-1,3,2-苯并二氧硼烷-2-甲胺
• 中文别名: (ALPHAR,3AS,4S,6S,7AR)-六氢-3A,5,5-三甲基-ALPHA-甲基-4,6-甲桥-1,3,2-苯并二氧硼烷-2-甲胺
• 英文名称: (+)-pinanediol (1R)-(1-aminoethyl)-1-boronate
• 英文别名: (R)-BoroAla-(+)-Pinanediol；(1R)-1-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]ethanamine
• CAS: 497165-15-8
• 化学式: C₁₂H₂₂BNO₂
• 分子量: 223.123
• InChiKey: AKMVYVLKQCECJH-GBVMLCMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 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：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (alphaR,3aS,4S,6S,7aR)-六氢-alpha,3a,5,5-四甲基-4,6-甲桥-1,3,2-苯并二氧硼烷-2-甲胺 、 (9S,12S,15S,18S)-12-((R)-1-(tert-butoxy)ethyl)-9-(4'-hexyl-[1,1'-biphenyl]-4-carboxamido)-2,2,15-trimethyl-4,10,13,16-tetraoxo-18-((1-(3-(2-phenyltetrahydro-5H-[1,3]dioxolo[4,5-c]pyrrol-5-yl)propyl)-1H-1,2,3-triazol-4-yl)methyl)-3-oxa-5,11,14,17-tetraazanonadecan-19-oic acid 在 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 二氯甲烷 为溶剂， 反应 1.1h， 生成
  参考文献：
  名称：

  硼酸酯连接的大环脂肽作为靶向大肠杆菌的I型信号肽酶的丝氨酸蛋白酶抑制剂

  摘要：

  I型信号肽酶在细菌生存能力中起着至关重要的作用，是一种有前途但未充分利用的抗菌药物靶标。鉴于抗菌药耐药率的稳定增长，我们开发了一种新型的大环脂肽，通过硼酸酯战斗部连接P2和P1'，能够抑制大肠杆菌I型信号肽酶（Ec LepB）并表现出良好的抗菌活性。大环环，肽序列和亲脂性尾巴的结构修饰使我们得到了14种新颖的大环硼酸酯。这可以表明，大环来讲是很好的耐受性的EcLepB抑制和抗菌活性。在合成的大环化合物中， 鉴定出低纳摩尔范围的有效酶抑制剂（例如化合物42f，Ec LepB IC 50 = 29 nM）也显示出良好的抗菌活性（例如化合物42b，大肠杆菌WT MIC = 16μg/ mL）。这里描述的独特的大环硼酸酯是基于以前发表的线性脂肽EcLepB抑制剂试图解决细胞毒性和溶血作用。我们在本文中显示，大环的结构变化会影响细胞毒性和溶血活性，这表明P2至P1'接头提供了优化脱靶效应的手段。然而

  DOI：

  10.1016/j.ejmech.2018.08.086
• 作为产物：
  描述：

  (1S,2S,6R,8S)-4-[(1S)-1-chloroethyl]-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decane 在 盐酸 、 正丁基锂 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 17.0h， 生成 (alphaR,3aS,4S,6S,7aR)-六氢-alpha,3a,5,5-四甲基-4,6-甲桥-1,3,2-苯并二氧硼烷-2-甲胺
  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

文献信息

• C-MYC PROTEIN INHIBITOR, AND PREPARATION METHOD THEREFOR AND USE THEREOF
  申请人：SUZHOU KINTOR PHARMACEUTICALS, INC.

  公开号：US20220324884A1

  公开（公告）日：2022-10-13

  Provided are a c-Myc protein inhibitor, and a preparation method therefor and use thereof. The c-Myc protein inhibitor selectively inhibits c-Myc protein. Therefore, the inhibitor can be used for prevention and treatment of diseases related to c-Myc protein disorders, such as cancers, cardiovascular and cerebrovascular diseases, diseases related to virus infection.

  提供一种c-Myc蛋白抑制剂及其制备方法和用途。该c-Myc蛋白抑制剂可以选择性地抑制c-Myc蛋白，因此可以用于预防和治疗与c-Myc蛋白异常相关的疾病，如癌症、心血管和脑血管疾病、与病毒感染相关的疾病。
• 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.
• Boronic ester-linked macrocyclic lipopeptides as serine protease inhibitors targeting Escherichia coli type I signal peptidase
  作者：Natalia Szałaj、Lu Lu、Andrea Benediktsdottir、Edouard Zamaratski、Sha Cao、Gustav Olanders、Charles Hedgecock、Anders Karlén、Máté Erdélyi、Diarmaid Hughes、Sherry L. Mowbray、Peter Brandt

  DOI：10.1016/j.ejmech.2018.08.086

  日期：2018.9

  Type I signal peptidase, with its vital role in bacterial viability, is a promising but underexploited antibacterial drug target. In the light of steadily increasing rates of antimicrobial resistance, we have developed novel macrocyclic lipopeptides, linking P2 and P1′ by a boronic ester warhead, capable of inhibiting Escherichia coli type I signal peptidase (EcLepB) and exhibiting good antibacterial

  I型信号肽酶在细菌生存能力中起着至关重要的作用，是一种有前途但未充分利用的抗菌药物靶标。鉴于抗菌药耐药率的稳定增长，我们开发了一种新型的大环脂肽，通过硼酸酯战斗部连接P2和P1'，能够抑制大肠杆菌I型信号肽酶（Ec LepB）并表现出良好的抗菌活性。大环环，肽序列和亲脂性尾巴的结构修饰使我们得到了14种新颖的大环硼酸酯。这可以表明，大环来讲是很好的耐受性的EcLepB抑制和抗菌活性。在合成的大环化合物中， 鉴定出低纳摩尔范围的有效酶抑制剂（例如化合物42f，Ec LepB IC 50 = 29 nM）也显示出良好的抗菌活性（例如化合物42b，大肠杆菌WT MIC = 16μg/ mL）。这里描述的独特的大环硼酸酯是基于以前发表的线性脂肽EcLepB抑制剂试图解决细胞毒性和溶血作用。我们在本文中显示，大环的结构变化会影响细胞毒性和溶血活性，这表明P2至P1'接头提供了优化脱靶效应的手段。然而