(S)-pinanediol (azidomethyl)boronate | 1043894-61-6

• 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: (S)-pinanediol (azidomethyl)boronate
• 英文别名: (+)-pinanediol α-azidomethaneboronate；(+)-pinanediol azidomethaneboronate
• CAS: 1043894-61-6
• 化学式: C₁₁H₁₈BN₃O₂
• 分子量: 235.094
• InChiKey: SADXNHORMSUHCP-CKEKPRIKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  67.22
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (S)-pinanediol (azidomethyl)boronate 在 zinc(II) chloride 作用下， 以 四氢呋喃 为溶剂， 生成 (+)-pinanediol (1R)-2-azido-1-[N,N-bis(trimethylsilyl)amino]ethaneboronate
  参考文献：
  名称：

  [EN] BORONIC ACID INHIBITORS OF BETA-LACTAMASES
  [FR] INHIBITEURS DE TYPE ACIDE BORONIQUE DE BÊTA-LACTAMASES

  摘要：

  这项发明涉及新型硼酸化合物，一种制备这种化合物的方法，用于制备这种化合物的中间化合物，用于制备这种化合物的方法中间化合物，一种药物组合物，上述一种或多种化合物或药物组合物在制造治疗细菌感染药物的药物制剂中的使用，以及一种筛选方法。

  公开号：

  WO2013053372A1
• 作为产物：
  描述：

  α-bromomethyl pinanediolboronate 在 sodium azide 、 四丁基溴化铵 作用下， 以 二氯甲烷 、 水 为溶剂， 生成 (S)-pinanediol (azidomethyl)boronate
  参考文献：
  名称：

  含硼的拟肽药物-一类新型的选择性抗结核药物

  摘要：

  由于新的多抗性菌株的出现，如今结核病的医学治疗变得复杂，因此，迫切需要新的抗生素。在这里，我们报告了一种新型的高选择性抗菌含硼拟肽化合物的合成和体外测试，该类化合物具有对结核分枝杆菌表现出≤5μg/ mL的活性。开发出的新方法使合成具有高非对映选择性的各种取代的β-氨基硼酸及其衍生物成为可能。

  DOI：

  10.1111/cbdd.12091

文献信息

• α‐Triazolylboronic Acids: A Promising Scaffold for Effective Inhibitors of KPCs
  作者：Maria Luisa Introvigne、Magdalena A. Taracila、Fabio Prati、Emilia Caselli、Robert A. Bonomo

  DOI：10.1002/cmdc.202000126

  日期：2020.7.20

  β‐lactamases. The selectivity and high potency of specific boronates bearing an amide side chain that mimics the β‐lactam's amide side chain have been advanced in several studies. Herein, we describe a new class of boronic acids in which the amide group is replaced by a bioisostere triazole. The boronic acids were obtained in a two‐step synthesis that relies on the solid and versatile copper‐catalyzed azide–alkyne

  硼酸是已知的丝氨酸β-内酰胺酶的可逆共价抑制剂。带有模拟β-内酰胺酰胺侧链的特定硼酸酯的选择性和高效力在多项研究中得到了进步。在此，我们描述了一类新的硼酸，其中酰胺基团被生物电子等排体三唑取代。硼酸是通过两步合成获得的，该合成依赖于固体且通用的铜催化叠氮化物-炔环加成（CuAAC），然后进行硼酸酯脱保护。所有化合物均对肺炎克雷伯菌碳青霉烯酶 KPC-2 表现出非常好的抑制作用，K i值范围为 1 nM 至 1 μM，并且大多数化合物能够恢复头孢吡肟对携带bla KPC-2 的肺炎克雷伯菌的活性。特别是，带有被噻吩环取代的磺酰胺的化合物1 e被证明是一种优异的 KPC-2 抑制剂（K i = 30 nM）；它恢复了 KPC-Kpn 细胞中头孢吡肟的敏感性 (MIC=0.5 μg/mL)，其值与伐波巴坦相似 ( K i =20 nM，KPC-Kpn 中的 MIC 0.5 μg/mL)。我们的研究结果表明，α-三唑基硼酸盐可能是治疗
• Synthesis of a (β-acetamido-α-acetoxyethyl)boronic ester via azido boronic esters
  作者：Donald S. Matteson、Davis Maliakal、Levente Fabry-Asztalos

  DOI：10.1016/j.jorganchem.2008.03.031

  日期：2008.6

  (Azidomethyl)boronic esters of 1,2-dicyclohexyl-1,2-ethanediol (“DICHED”) and pinanediol have been prepared from the corresponding (bromomethyl)boronic esters. Conversion to (2-azido-1-chloro- or bromoethyl)boronic esters by reaction with a (dihalomethyl)lithium followed. Attempted displacement of halide from DICHED (2-azido-1-haloethyl)boronates with alkoxides failed. Reaction of either pinanediol

  由相应的（溴甲基）硼酸酯已经制备了1，2-二环己基-1，2-乙二醇（“叠氮基”）硼酸酯（“ DICHED”）和pin烷二醇。然后通过与（二卤甲基）锂反应转化为（2-叠氮基-1-氯-或溴乙基）硼酸酯。尝试用醇盐从DICHED（2-叠氮基-1-卤代乙基）硼酸酯中取代卤化物失败。pin烷二醇或DICHED（2-叠氮基-1-氯甲基）硼酸酯与乙酸钠在乙酸中的反应生成1-乙酰氧基衍生物，为约1：1的非对映异构体混合物，表明α-硼烷基碳正离子中间体可能参与其中。在氯化氢在二恶烷溶液中的铂上的pin烷二醇叠氮基硼酸酯在铂上的氢化伴随脱乙酰基化反应，形成不纯的（2-氨基-1-羟乙基）硼酸酯盐酸盐。尝试纯化该物质导致脱硼为乙醇胺。乙酰化得到pin二醇（2-乙酰氨基-1-乙酰氧基乙基）硼酸酯。
• COMPOSITIONS AND METHODS OF TREATING OF BACTERIAL INFECTIONS WITH BETA-LACTAMASE INHIBITORS
  申请人：CASE WESTERN RESERVE UNIVERSITY

  公开号：US20170065626A1

  公开（公告）日：2017-03-09

  A method of treating a bacterial infection in a subject in need thereof includes administering to the subject therapeutically effective amounts of at least one β-lactam antibiotic and at least one triazolylmethyl boronic acid.

  治疗需要的受试者体内细菌感染的方法包括向受试者投予至少一种β-内酰胺类抗生素和至少一种三唑基甲硼酸的治疗有效剂量。
• Biochemical and Structural Analysis of Inhibitors Targeting the ADC-7 Cephalosporinase of <i>Acinetobacter baumannii</i>
  作者：Rachel A. Powers、Hollister C. Swanson、Magdalena A. Taracila、Nicholas W. Florek、Chiara Romagnoli、Emilia Caselli、Fabio Prati、Robert A. Bonomo、Bradley J. Wallar

  DOI：10.1021/bi500887n

  日期：2014.12.9

  beta-Lactam resistance in Acinetobacter baumannii presents one of the greatest challenges to contemporary antimicrobial chemotherapy. Much of this resistance to cephalosporins derives from the expression of the class C beta-lactamase enzymes, known as Acinetobacter-derived cephalosporinases (ADCs). Currently, beta-lactamase inhibitors are structurally similar to beta-lactam substrates and are not effective inactivators of this class C cephalosporinase. Herein, two boronic acid transition state inhibitors (BATSIs S02030 and SM23) that are chemically distinct from beta-lactams were designed and tested for inhibition of ADC enzymes. BATSIs SM23 and S02030 bind with high affinity to ADC-7, a chromosomal cephalosporinase from Acinetobacter baumannii (K-i = 21.1 +/- 1.9 nM and 44.5 +/- 2.2 nM, respectively). The X-ray crystal structures of ADC-7 were determined in both the apo form (1.73 angstrom resolution) and in complex with S02030 (2.0 angstrom resolution). In the complex, S02030 makes several canonical interactions: the O1 oxygen of S02030 is bound in the oxyanion hole, and the R1 amide group makes key interactions with conserved residues Asn152 and Gln120. In addition, the carboxylate group of the inhibitor is meant to mimic the C-3/C-4 carboxylate found in beta-lactams. The C-3/C-4 carboxylate recognition site in class C enzymes is comprised of Asn346 and Arg349 (AmpC numbering), and these residues are conserved in ADC-7. Interestingly, in the ADC-7/S02030 complex, the inhibitor carboxylate group is observed to interact with Arg340, a residue that distinguishes ADC-7 from the related class C enzyme AmpC. A thermodynamic analysis suggests that Delta H driven compounds may be optimized to generate new lead agents. The ADC-7/BATSI complex provides insight into recognition of non-beta-lactam inhibitors by ADC enzymes and offers a starting point for the structure-based optimization of this class of novel beta-lactamase inhibitors against a key resistance target.
• Click Chemistry in Lead Optimization of Boronic Acids as β-Lactamase Inhibitors
  作者：Emilia Caselli、Chiara Romagnoli、Roza Vahabi、Magdalena A. Taracila、Robert A. Bonomo、Fabio Prati

  DOI：10.1021/acs.jmedchem.5b00341

  日期：2015.7.23

  Boronic acid transition-state inhibitors (BAT-SIs) represent one of the most promising classes of beta-lactamase inhibitors. Here we describe a new class of BATSIs, namely, 1-amido-2-triazolylethaneboronic acids, which were synthesized by combining the asymmetric homologation of boronates with copper-catalyzed azide-alkyne cycloaddition for the stereoselective insertion of the amido group and the regioselective formation of the 1,4-disubstituted triazole, respectively. This synthetic pathway, which avoids intermediate purifications, proved to be flexible and efficient, affording in good yields a panel of 14 BATSIs bearing three different R1 amide side chains (acetamido, benzylamido, and 2-thienylacetamido) and Several R substituents on the triazole. This small library was tested against two clinically relevant class C beta-lactamases from Enterobacter spp. and Pseudomonas aeruginosa. The K-i value of the best compound (13a) was as low as 4 nM with significant reduction of bacterial resistance to the combination of cefotaxime/13a.