【作者】 周树宝；

【导师】 曹玲华；

【作者基本信息】 新疆大学 ， 有机化学， 2010， 硕士

【摘要】 4-色满酮类化合物具有广泛的生物活性,如抗血小板聚集、抗炎、抗真菌、酶抑制、抗心律不齐、抗雌激素、抗氧化和抗肿瘤等活性,它的还原产物色满类化合物也是一类重要的医药中间体。含氟有机化合物具有较高的脂溶性和疏水性,能明显改善化合物的生物活性,因此,含氟4-色满酮的合成是色满酮类药物中间体的一个重要发展方向。具有生物活性的4-色满酮多数具有手性。近年来,合成立体结构专一的4-色满酮也已成为该领域的研究热点。本文以5-氟-2-羟基苯乙酮为原料,采用两种不同的催化体系,分别合成了6-氟-2-烷基-4-色满酮和6-氟-2-芳基-4-色满酮两类化合物。反应条件温和,产率较高。另外,选择6-氟-2-苯基-4-色满酮为研究对象,对其不对称反应产物:(2R)-6-氟-2-苯基-4-色满酮的合成方法进行了探索。所得产物结构经IR,1H NMR,13C NMR和HRMS谱证实。本论文的主要工作:1.以5-氟-2-羟基苯乙酮为原料,四氢吡咯为催化剂,乙醇为溶剂,回流条件下合成了6-氟-2-烷基-4-色满酮类化合物;2.以5-氟-2-羟基苯乙酮为原料,四氢吡咯为催化剂,乙醇为溶剂,室温反应得到中间体2′-羟基查尔酮,进而在BF3·OEt2催化条件下,发生分子内氧杂Michael加成反应,合成了6-氟-2-芳基-4-色满酮类化合物;3.以5-氟-2-羟基苯乙酮为原料,分别在四种有机小分子手性催化剂作用下,乙醇为溶剂,与苯甲醛室温反应,生成6-氟-2-苯基-4-色满酮,对其不对称合成方法进行了探索;4.对6-氟-2-烷基/芳基-4-色满酮的荧光活性进行了测试,讨论了不同基团对化合物荧光活性的影响。更多还原

【Abstract】 Chroman-4-ones have a broad array of biological activity, such as antiplatelet aggregation, antiinflammatory, antifungal, enzyme inhibition, antiarrhythmic, antiestrogen, antioxidant and anticancer, and chromans, as the reduction products of chroman-4-ones, are important pharmaceutical intermediates. Moreover, fluorine substitution is commonly used in contemporary medicinal chemistry with high fat-soluble and hydrophobic, can significantly improve the biological activity of the compounds. Synthesis of fluoro-containing chroman-4-ones is an important direction of pharmaceutical development. Chiral chroman-4-ones often have remarkable biological activity, therefore, the asymmetric synthesis of chroman-4-ones become a hot research topic in recent years.In this paper, 6-fluoro-2-alkylchroman-4-ones and 6-fluoro-2-arylchroman-4-ones were synthesized in high yields from 5-fluoro-2-hydroxyacetophenone by using two different catalysts. In addition, based on 6-fluoro-2-phenylchroman-4-one, the asymmetric synthesis method of (2R)-6-fluoro-2-phenylchroman-4-one was explored. The products were characterized by IR, 1H NMR, 13C NMR and HRMS spectral data.This work is composed of the follows:1. A series of 6-fluoro-2-alkylchroman-4-ones were obtained from 5-fluoro-2-hydroxy- acetophenone by using pyrrolidine as catalyst in anhydrous EtOH in the condition of refluxing.2. 2′-Hydroxychalcones were synthesized from 5-fluoro-2-hydroxyacetophenone by using pyrrolidine as catalyst in anhydrous EtOH at room temperature. Then, a series of 6-fluoro-2-arylchroman-4-ones were synthesized from 2′-hydroxychalcones by intramolecular oxa-Michael addition catalyzed by BF3·OEt2.3. 6-Fluoro-2-phenylchroman-4-one was prepared from 5-fluoro-2-hydroxyacetophenone and benzaldehyde by using four different kinds of organic catalysts in anhydrous EtOH at room temperature, and their asymmetric synthesis conditions were studied. 4. The fluorescence activity of 6-fluoro-2-alkyl/arylchroman-4-ones was detected and the affect of different substituted groups was investigated.更多还原