(3S,6S)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-chloro-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate | 1681053-96-2

• 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: (3S,6S)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-chloro-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate
• 英文别名: 4,6-Methano-1,3,2-benzodioxaborole-2-hexanoic acid, epsilon-chloro-beta-[[(1,1-dimethylethyl)dimethylsilyl]oxy]hexahydro-3a,5,5-trimethyl-, 1,1-dimethylethyl ester, (betaS,epsilonS,3aS,4S,6S,7aR)-；tert-butyl (3S,6S)-3-[tert-butyl(dimethyl)silyl]oxy-6-chloro-6-[(1S,2S,6R,8S)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl]hexanoate
• CAS: 1681053-96-2
• 化学式: C₂₆H₄₈BClO₅Si
• 分子量: 515.014
• InChiKey: IGECAYLIZBERQG-LZZOSOCDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.76
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-噻吩乙酸 、 (3S,6S)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-chloro-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate 在 2-噻吩乙酸 作用下， 以70的产率得到(3S,6R)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-(2-thiophen-2-yl-acetylamino)-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate
  参考文献：
  名称：

  J. Med. Chem. 2015, 58, 3682-3692

  摘要：

  DOI：
• 作为产物：
  描述：

  (3S)-tert-butyl 3-(tert-butyldimethylsilyloxy)-5-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]pentanoate 以88的产率得到(3S,6S)-tert-butyl 3-(tert-butyldimethylsilyloxy)-6-chloro-6-[(2S,6R)-2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.0^2,6]decan-4-yl]hexanoate
  参考文献：
  名称：

  J. Med. Chem. 2015, 58, 3682-3692

  摘要：

  DOI：

文献信息

• [EN] SYNTHESIS OF BORONATE SALTS AND USES THEREOF<br/>[FR] SYNTHÈSE DE SELS BORONATE ET UTILISATIONS DE CEUX-CI
  申请人：REMPEX PHARMACEUTICALS INC

  公开号：WO2015171430A1

  公开（公告）日：2015-11-12

  Disclosed herein are boronate intermediates in the synthesis of antimicrobial compounds and the use and preparation thereof. Some embodiments relate to crystalline boronate salt derivatives and their use in the synthesis of therapeutic compounds.

  本文披露了在合成抗微生物化合物过程中的硼酸酯中间体及其使用和制备。一些实施例涉及结晶硼酸盐衍生物及其在合成治疗化合物中的使用。
• Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases
  作者：Scott J. Hecker、K. Raja Reddy、Maxim Totrov、Gavin C. Hirst、Olga Lomovskaya、David C. Griffith、Paula King、Ruslan Tsivkovski、Dongxu Sun、Mojgan Sabet、Ziad Tarazi、Matthew C. Clifton、Kateri Atkins、Amy Raymond、Kristy T. Potts、Jan Abendroth、Serge H. Boyer、Jeffrey S. Loutit、Elizabeth E. Morgan、Stephanie Durso、Michael N. Dudley

  DOI：10.1021/acs.jmedchem.5b00127

  日期：2015.5.14

  The increasing dissemination of carbapenemases in Gram-negative bacteria has threatened the clinical usefulness of the beta-lactam class of antimicrobials. A program was initiated to discover a new series of serine beta-lactamase inhibitors containing a boronic acid pharmacophore, with the goal of finding a potent inhibitor of serine carbapenemase enzymes that are currently compromising the utility of the carbapenem class of antibacterials. Potential lead structures were screened in silico by modeling into the active sites of key serine beta-lactamases. Promising candidate molecules were synthesized and evaluated in biochemical and whole-cell assays. Inhibitors were identified with potent inhibition of serine carbapenemases, particularly the Klebsiella pneumoniae carbapenemase (KPC), with no inhibition of mammalian serine proteases. Studies in vitro and in vivo show that RPX7009 (9f) is a broad-spectrum inhibitor, notably restoring the activity of carbapenems against KPC-producing strains. Combined with a carbapenem, 9f is a promising product for the treatment of multidrug resistant Gram-negative bacteria.