(S)-pinanediol (2-azido-1-chloroethyl)boronate | 1043894-62-7

• 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 (2-azido-1-chloroethyl)boronate
• 英文别名: (+)-pinanediol 1R-chloro-2-azidoethaneboronate；(+)-pinanediol (1S)-chloro-2-azidoethaneboronate；(S)-pinanediol (1-chloro-2-azidoethyl)boronate；(1S,2S,6R,8S)-4-[(1S)-2-azido-1-chloroethyl]-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decane
• CAS: 1043894-62-7
• 化学式: C₁₂H₁₉BClN₃O₂
• 分子量: 283.566
• InChiKey: ZLOCXNLMNMRTCJ-YOQJGNTNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.17
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-pinanediol (2-azido-1-chloroethyl)boronate 在 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 1.17h， 生成
  参考文献：
  名称：

  Click Chemistry in Lead Optimization of Boronic Acids as β-Lactamase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/acs.jmedchem.5b00341
• 作为产物：
  描述：

  α-bromomethyl pinanediolboronate 在 正丁基锂 、 sodium azide 、 四丁基溴化铵 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成 (S)-pinanediol (2-azido-1-chloroethyl)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

• 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。
• [EN] HETEROCYCLIC BORONIC ACID ESTER DERIVATIVES AND THERAPEUTIC USES THEREOF<br/>[FR] DÉRIVÉS D'ESTER D'ACIDE BORONIQUE HÉTÉROCYCLIQUE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：REMPEX PHARMACEUTICALS INC

  公开号：WO2013033461A1

  公开（公告）日：2013-03-07

  Disclosed herein are antimicrobial compounds compositions, pharmaceutical compositions, the use and preparation thereof. Some embodiments relate to cyclic boronate compounds and their use as therapeutic agents.

  本文揭示了抗微生物化合物组合物、药物组合物及其使用和制备。一些实施例涉及环硼酸酯化合物及其用作治疗剂的用途。
• [EN] BORONIC ACID INHIBITORS OF BETA-LACTAMASES<br/>[FR] INHIBITEURS DE TYPE ACIDE BORONIQUE DE BÊTA-LACTAMASES
  申请人：THERABOR PHARMACEUTICALS

  公开号：WO2013053372A1

  公开（公告）日：2013-04-18

  The invention relates to novel boronic acid compounds, a method for the preparation of such compounds, intermediate compounds for the preparation of such compounds, intermediate compounds for the use in a method for preparation of such compounds, a pharmaceutical composition, the use of one or more compounds discussed above or of a pharmaceutical composition in the manufacture of a medicament for the treatment of a bacterial infection, and a screening method.

  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。
• Broad-spectrum cyclic boronate β-lactamase inhibitors featuring an intramolecular prodrug for oral bioavailability
  作者：K. Raja Reddy、Maxim Totrov、Olga Lomovskaya、David C. Griffith、Ziad Tarazi、Matthew C. Clifton、Scott J. Hecker

  DOI：10.1016/j.bmc.2022.116722

  日期：2022.5

  efforts to broaden the spectrum and potency of cyclic boronic acid β-lactamase inhibitor vaborbactam included a series of 7-membered ring boronates. Exploration of stereoisomers and incorporation of heteroatoms allowed identification of the all-carbon cyclic boronate with substituents trans as the preferred core structure, showing inhibition of Class A and C enzymes. Crystal structures of one analog

  早期扩大环状硼酸 β-内酰胺酶抑制剂 vaborbactam 的范围和效力的努力包括一系列 7 元环硼酸盐。对立体异构体的探索和杂原子的掺入允许鉴定具有取代基的全碳环状硼酸盐作为优选的核心结构，显示出对 A 类和 C 类酶的抑制作用。获得了与重要的β-内酰胺酶结合的一种类似物的晶体结构。当在酸性条件下分离时，这些化合物自发形成中性环状酸酐（分子内前药），与开环羧酸盐（9%）相比，其口服生物利用度（52-69%）显着提高。
• 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.