8-bromo-6-chloro-chromen-2-one | 188813-16-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 8-bromo-6-chloro-chromen-2-one
• 英文别名: 8-bromo-6-chloro-2H-1-benzopyran-2-one；8-bromo-6-chloro-2H-chromen-2-one；8-bromo-6-chlorochromen-2-one
• CAS: 188813-16-3
• 化学式: C₉H₄BrClO₂
• 分子量: 259.487
• InChiKey: SKHMMUFWOTWUKU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-bromo-6-chloro-chromen-2-one 在 盐酸 、 immobilized Pseudomonas cepacia lipase 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 30.0h， 生成 ethyl (3R)-3-amino-3-(3-bromo-5-chloro-2-hydroxyphenyl)propanoate
  参考文献：
  名称：

  R-Isomers of Arg-Gly-Asp (RGD) mimics as potent αvβ3 inhibitors

  摘要：

  The integrin alpha(v)beta(3), vitronectin receptor, is expressed in a number of cell types and has been shown to mediate adhesion of osteoclasts to bone matrix, vascular smooth muscle cell migration, and angiogenesis. We recently disclosed the discovery of a tripeptide Arg-Gly-Asp (RGD) mimic, which has been shown to be a potent inhibitor of the integrin alpha(v)beta(3) and has excellent anti-angiogenic properties including its suppression of tumor growth in animal models. In other investigations involving RGD mimics, only compounds containing the S-isomers of the beta-amino acids have been shown to be potent. We were surprised to find the potencies of analogs containing enantiomerically pure S-isomers of beta-amino acids which were only marginally better than the corresponding racemic mixtures. We therefore synthesized RGD mimics containing R-isomers of beta-amino acids and found them to be relatively potent inhibitors of alpha(v)beta(3). One of the compounds was examined in tumor models in mice and has been shown to significantly reduce the rate of growth and the size of tumors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.034
• 作为产物：
  描述：

  3-溴-5-氯水杨醛 在 乙酸酐 、 三乙胺 作用下， 生成 8-bromo-6-chloro-chromen-2-one
  参考文献：
  名称：

  R-Isomers of Arg-Gly-Asp (RGD) mimics as potent αvβ3 inhibitors

  摘要：

  The integrin alpha(v)beta(3), vitronectin receptor, is expressed in a number of cell types and has been shown to mediate adhesion of osteoclasts to bone matrix, vascular smooth muscle cell migration, and angiogenesis. We recently disclosed the discovery of a tripeptide Arg-Gly-Asp (RGD) mimic, which has been shown to be a potent inhibitor of the integrin alpha(v)beta(3) and has excellent anti-angiogenic properties including its suppression of tumor growth in animal models. In other investigations involving RGD mimics, only compounds containing the S-isomers of the beta-amino acids have been shown to be potent. We were surprised to find the potencies of analogs containing enantiomerically pure S-isomers of beta-amino acids which were only marginally better than the corresponding racemic mixtures. We therefore synthesized RGD mimics containing R-isomers of beta-amino acids and found them to be relatively potent inhibitors of alpha(v)beta(3). One of the compounds was examined in tumor models in mice and has been shown to significantly reduce the rate of growth and the size of tumors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.03.034

文献信息

• Pilot Plant Preparation of an α_vβ₃ Integrin Antagonist. Part 1. Process Research and Development of a (<i>S</i>)-β-Amino Acid Ester Intermediate:  Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction
  作者：Jerry D. Clark、Gerald A. Weisenburger、D. Keith Anderson、Pierre-Jean Colson、Albert D. Edney、Donald J. Gallagher、H. Peter Kleine、Carl M. Knable、Melissa K. Lantz、Christine M. V. Moore、James B. Murphy、Thomas E. Rogers、Peter G. Ruminski、Ajit S. Shah、Neil Storer、Bruce E. Wise

  DOI：10.1021/op034094j

  日期：2004.1.1

  enantioselective method for preparing (S)-β-amino acid ester 3, a key intermediate to the αvβ3 integrin antagonist 1. Reported are an asymmetric Michael reaction approach, attempts to enantioselectively hydrogenate an enamine, resolution of (±)-3 via diastereomeric salt formation, and a synthetic route employing a novel, diastereoselective imino-Reformatsky reaction. This last research initiative proved

  描述了四项过程研究调查，旨在辨别制备 (S)-β-氨基酸酯 3（αvβ3 整合素拮抗剂 1 的关键中间体）的可扩展的对映选择性方法。报告的是不对称迈克尔反应方法，试图对映选择性氢化烯胺，通过非对映体盐的形成拆分 (±)-3，以及采用新型非对映选择性亚氨基-Reformatsky 反应的合成路线。最后一项研究计划被证明是成功的，并被用作初始 API 供应的促成途径。报道了这种使能化学的工艺开发。研究和优化的技术问题是（1）在亚氨基-Reformatsky反应中采用MEM保护以获得高产率和非对映选择性的必要性，
• Amine-Catalyzed Cascade Synthesis of 3,4-Diunsubstituted Coumarins
  作者：Jia Wei、Pengcheng Wang、Qianfa Jia、Jiaoyao Huang、Zhiyun Du、Kun Zhang、Jian Wang

  DOI：10.1002/ejoc.201300538

  日期：2013.7

  We disclose an efficient route to synthesize 3,4-diunsubstituted coumarins through a cascade organocatalytic reaction. The reaction is catalyzed by using of a combination of benzylamine (10 mol-%) and triethylamine (10 mol-%). Various salicylaldehydes were tested, and the corresponding coumarin products were obtained in good to high yields under mild and metal-free reaction conditions.

  我们公开了一种通过级联有机催化反应合成 3,4-二未取代香豆素的有效途径。该反应通过使用苄胺（10 mol-%）和三乙胺（10 mol-%）的组合来催化。测试了各种水杨醛，并在温和且无金属的反应条件下以良好至高产率获得了相应的香豆素产物。
• Antibacterial Agents
  申请人：Miller William Henry

  公开号：US20090054418A1

  公开（公告）日：2009-02-26

  2H-chromen-2-one derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.

  本文揭示了用于治疗哺乳动物，尤其是人类细菌感染的2H-香豆素衍生物。
• Antibacterial agents
  申请人：Glaxo Group Limited

  公开号：US07709496B2

  公开（公告）日：2010-05-04

  2H-chromen-2-one derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.

  本文披露了对哺乳动物，尤其是人类治疗细菌感染有用的2H-香豆素衍生物。
• Water-promoted catalytic hydrodecarboxylation of conjugated carboxylic acids under open air conditions at room temperature
  作者：Zhan-Yong Wang、Ting Yang、Kai-Kai Wang、Dongfang Liu、Xueji Ma、Nan Wang、Hong Liu、aili Sun、Hongxin Liu

  DOI：10.1039/d3gc00351e

  日期：——

  A water-promoted DABCO-organocatalyzed hydrodecarboxylation of conjugated carboxylic acids has been developed, providing the corresponding decarboxylation products in good to excellent yields. This metal-, photocatalyst-, and oxidants-free protocol features high functional...

  我们开发出了一种水促进 DABCO 有机催化共轭羧酸加氢脱羧反应，可提供相应的脱羧产物，产率从良好到极佳。这种不含金属、光催化剂和氧化剂的方案具有高官能度、高活性和低成本的特点。