CN104892556B - 一类二苯乙烯香豆素类衍生物及其制备方法与用途 - Google Patents

一类二苯乙烯香豆素类衍生物及其制备方法与用途 Download PDF

Info

Publication number
CN104892556B
CN104892556B CN201510290010.8A CN201510290010A CN104892556B CN 104892556 B CN104892556 B CN 104892556B CN 201510290010 A CN201510290010 A CN 201510290010A CN 104892556 B CN104892556 B CN 104892556B
Authority
CN
China
Prior art keywords
compound
preparation
stilbene
coumarin derivatives
salicylide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201510290010.8A
Other languages
English (en)
Other versions
CN104892556A (zh
Inventor
阮班锋
程慧洁
李红林
杨亿弟
李青山
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Huangshan Development Investment Group Co.,Ltd.
Original Assignee
Hefei University of Technology
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hefei University of Technology filed Critical Hefei University of Technology
Priority to CN201510290010.8A priority Critical patent/CN104892556B/zh
Publication of CN104892556A publication Critical patent/CN104892556A/zh
Application granted granted Critical
Publication of CN104892556B publication Critical patent/CN104892556B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/08—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring
    • C07D311/12—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 not hydrogenated in the hetero ring substituted in position 3 and unsubstituted in position 7

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)

Abstract

本发明公开了一类二苯乙烯香豆素类衍生物及其制备方法与用途，涉及药物合成技术领域，其结构通式如式(1)所示：

Description

一类二苯乙烯香豆素类衍生物及其制备方法与用途
技术领域
本发明涉及药物合成技术领域，具体涉及一类新型二苯乙烯香豆素类衍生物及制备方法与用途。
背景技术
香豆素是具有苯并α-吡喃酮结构的一类化合物，它在不同种属的植物中都具有广泛的分布和用途，特别是在伞形科、芸香科、菊科、豆科、茄科等植物中，也存在于动物和微生物中，如发光真菌的亮菌素类、海洋真菌中分离出的异香豆素等。香豆素类化合物具有十分重要的药理作用，如抗肿瘤、抗HIV、抗氧化、抗心律失常、抗炎镇痛及抗菌。
香豆素的抗肿瘤活性引起了国内外的广泛关注。华法林钠是最早应用于抗癌研究的香豆素(The Johns Hopkins Medical Journal,1968,123(6):305)，它对V2癌细胞株具有明显的生物活性。Ngo等从越南滇南溪桫中分离出多种香豆素(Chemical andPharmaceutical Bulletin,2010,58(11):1487)，其中以(E)-4-(1-羟丙基)-5,7-二羟基-6-(3,7-二甲基-2,6-辛二烯基)-8-(3-甲基-1-氧代丁基)香豆素为代表化合物，能抑制多种癌细胞株的生长。香豆素同时还表现出抗炎活性，可以在水肿液中产生刺激促使机体产生相应的酶而消除蛋白等物质，因此可以用于治疗水肿(British Journal ofExperimental Pathology,1975,56(6):554)。化合物白茅苷在体外研究中表现出对脂多糖刺激的小鼠巨噬细胞有抗炎作用(Journal of Agricultural and Food Chemistry,2012,60(7),1673)。
天然产物白藜芦醇是一种具有二苯乙烯骨架的植物抗毒素，属于黄酮类的多酚化合物。1939年首次从毛叶藜芦的根部提取而获得，在自然界中广泛存在于葡萄、红酒、桑椹、花生等植物中，具有顺式和反式两种结构，在紫外照射下可以相互转化，自然界中主要以反式结构存在。它具有广泛的药理作用，如抗癌症、抗氧化、抗菌抗炎、神经作用和对肝脏的保护作用等。由于它具有选择性差、结构单一以及生物利用度低等特点，因此目前的研究热点集中在对其衍生物的开发，以期筛选出高效、低毒且选择性好的二苯乙烯类衍生物。
依据药物拼合原理以及药物分子的结构设计理念，本发明在白藜芦醇的二苯乙烯分子骨架上引入香豆素结构，设计和合成出了一系列新型二苯乙烯-香豆素杂合型分子，并且生物活性测试结果表明这类化合物对单胺氧化酶(MAO-A和MAO-B)具有良好的抑制活性，并且对MAO-B有着良好的选择性。
发明内容
本发明所要解决的技术问题在于提供一种对单胺氧化酶具有良好抑制活性的新型二苯乙烯香豆素类衍生物及制备方法与用途。
本发明所要解决的技术问题采用以下的技术方案来实现：
一类二苯乙烯香豆素类衍生物，其结构通式如式(1)所示：
其中R1选自-H、-OCH3、-CH3、-Br或-OCH2CH3；R2选自-H、-OCH3、-CH3、-Cl、-Br、-OCH2CH3或-N(CH3)2；R3选自-H、-OCH3、-CH3、-F、-Cl、-Br或-CH2CH＝CH2；R4选自-H或-OCH3。
上述二苯乙烯香豆素类衍生物的制备方法，包括下列步骤：
(1)先向N,N-二甲基甲酰胺中加入白藜芦醇三甲醚(a)，然后于冰浴中缓慢滴加三氯氧磷，滴加完毕后恢复至室温反应，1h后停止反应，随后将反应液逐滴加入到冰水与乙酸乙酯的混合溶液中，再分次加入碳酸钠固体直至无气泡产生，搅拌过夜后析出淡黄色固体，抽滤、干燥，最后柱层析分离得到化合物A：
(2)先向乙酰乙酸乙酯中加入取代水杨醛(b)，再加入哌啶，搅拌5min后加入无水乙醇，继续搅拌反应直至不再产生沉淀，随后反应液抽滤，同时先用石油醚洗涤，再用少量乙醇洗涤，最后干燥后得到化合物B：
(3)向无水乙醇中加入化合物A和化合物B，所得混合液于45℃水浴条件搅拌反应5min，再加入哌啶，反应24h后停止反应，抽滤、干燥，最后柱层析分离得到目标产物。
其中：步骤(2)中所述取代水杨醛的通式如(2)所示：
其中R1选自-H、-OCH3、-CH3、-Br或-OCH2CH3；R2选自-H、-OCH3、-CH3、-Cl、-Br、-OCH2CH3或-N(CH3)2；R3选自-H、-OCH3、-CH3、-F、-Cl、-Br或-CH2CH＝CH2；R4选自-H或-OCH3。
步骤(1)中所述白藜芦醇三甲醚与所述三氯氧磷的摩尔比为1:1，冰水与乙酸乙酯的体积比为5:1，N,N-二甲基甲酰胺的用量为每毫摩尔白藜芦醇三甲醚用0.5mL。
步骤(2)中所述乙酰乙酸乙酯与所述取代水杨醛的摩尔比为1:1，哌啶的用量为每毫摩尔乙酰乙酸乙酯用0.05mL，无水乙醇的用量为每毫摩尔取代水杨醛用1mL。
步骤(3)中所述化合物A与所述化合物B的摩尔比为1.5:1，哌啶的用量为每毫摩尔化合物B用0.05mL，无水乙醇的用量为每毫摩尔化合物B用10mL。
本发明还公开了上述二苯乙烯香豆素类衍生物在制备单胺氧化酶抑制剂中的应用。
本发明的有益效果是：
(1)本发明的合成路线的工艺简单易行，且反应收率较高；
(2)本发明所合成的化合物对单胺氧化酶具有良好的抑制活性及选择性；
(3)本发明可对筛选得到的较优化合物结构进行进一步优化，从而提高其对单胺氧化酶的抑制活性及选择性。
具体实施方式
为了使本发明实现的技术手段、创作特征、达成目的与功效易于了解，下面结合具体实施例，进一步阐述本发明。
实施例1：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧基苯乙烯基)苯基)丙烯酰基)-2H-吡喃-2-酮(化合物1)的制备
(1)取100mL圆底烧瓶，在冰水浴下加入N,N-二甲基甲酰胺(30mL)，另外称取白藜芦醇三甲醚(13.5g，0.075mol)，用10mL N,N-二甲基甲酰胺溶解，然后将其加入圆底烧瓶中，再缓慢滴加三氯氧磷(7mL，0.075mol)，滴加完毕后恢复至室温反应，搅拌反应1h。反应结束后取一个1000mL烧杯，加500mL冰水和100mL乙酸乙酯，然后将反应液逐滴加入其中，搅拌下分次加入碳酸钠固体直至无气泡产生，过夜析出淡黄色固体，抽滤、干燥，柱层析得(E)-2,4-二甲氧基-6-(4-甲氧基苯乙烯)苯甲醛(化合物A)。产物为黄色固体，收率92.7％，熔点108-109℃。1H NMR(DMSO-d6):3.78(s,3H),3.90(s,3H),3.92(s,3H),6.63(s,1H),6.91(s,1H),6.97(d,2H,J＝7.9Hz),7.21(d,1H,J＝16.2Hz),7.50(d,2H,J＝7.9Hz),7.95(d,1H,J＝16.2Hz),10.41(s,1H).MS(ESI):299.3(C18H18O4,[M+H]+)。
(2)在100mL圆底烧瓶中加入乙酰乙酸乙酯(10mmol，1.26mL)、水杨醛(10mmol,1.22g)，再加入哌啶(0.5mL)，室温搅拌5min后加入无水乙醇(10mL)，继续搅拌反应直至不再产生沉淀为止，真空抽滤，然后先用石油醚将颜色脱去，再用少量乙醇洗涤，静置烘干，得到化合物3-乙酰基-2H-苯并吡喃-2-酮。
(3)室温下先向100mL圆底烧瓶中加入无水乙醇(10mL)，再加入化合物A(1.5mmol,0.447g)和3-乙酰基-2H-苯并吡喃-2-酮(1.0mmol,0.188g)，混合物于45℃水浴条件搅拌反应5min，再加入哌啶(0.5mL)。反应24h后撤去水浴真空抽滤，取滤饼干燥后柱层析得到化合物1。产物为淡黄色固体粉末，收率是75％，熔点110-113℃。1H NMR(600MHz,DMSO)δ8.58(s,1H),7.99(d,J＝15.9Hz,1H),7.88(d,J＝7.6Hz,1H),7.70(dd,J＝11.4,4.2Hz,1H),7.52(dd,J＝14.6,12.4Hz,3H),7.42(d,J＝8.3Hz,1H),7.38(t,J＝7.5Hz,1H),7.31(t,J＝13.4Hz,1H),7.11–7.03(m,1H),6.88(d,J＝8.6Hz,2H),6.81(d,J＝1.8Hz,1H),6.56(d,J＝1.7Hz,1H),3.86(d,J＝5.6Hz,6H),3.75(s,3H).13C NMR(151MHz,DMSO)δ190.68(s),164.97(s),163.98(s),162.36(s),161.57(s),157.43(s),149.66(s),144.62(s),141.43(s),137.13(s),135.39(s),133.41(s),132.45(s),131.33(s),129.72(s),128.85(s),128.00(s),127.14(s),121.46(s),119.24(s),117.49(s),117.22(s),107.13(s),100.83(s),59.04(s),58.63(s),58.25(s).MS(EI):469.16(C29H24O6,[M+H]+).Anal.Calcd forC29H24O6:C,74.35；H,5.16；O,20.49％；Found:C,74.33；H,5.16；O,20.51％.
实施例2：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-8-甲氧基-2H-苯并吡喃-2-酮(化合物2)的制备
制备方法同实施例1。区别在于以3-甲氧基水杨醛代替水杨醛，得到黄棕色固体粉末目标化合物，收率63％，熔点115-116℃。1H NMR(600MHz,CDCl3)δ8.44(s,1H),8.23(d,J＝15.7Hz,1H),7.92(d,J＝15.7Hz,1H),7.49(d,J＝8.7Hz,2H),7.38(d,J＝16.0Hz,1H),7.22(d,J＝7.9Hz,1H),7.18(dd,J＝7.8,1.3Hz,1H),7.13(dd,J＝8.0,1.2Hz,1H),6.91(dd,J＝17.3,12.4Hz,3H),6.71(d,J＝2.3Hz,1H),6.41(d,J＝2.3Hz,1H),3.96(s,3H),3.91(s,3H),3.88(s,3H),3.83(s,3H).13C NMR(151MHz,cdcl3)δ190.23(s),164.60(s),164.03(s),162.26(s),161.19(s),149.77(s),149.68(s),147.46(s),145.20(s),141.81(s),135.04(s),132.52(s),130.89(s),129.21(s),129.07(s),127.55(s),127.19(s),123.61(s),121.91(s),118.43(s),117.99(s),116.81(s),106.38(s),100.21(s),58.95(s),58.31(s),58.09(s),57.97(s).MS(EI):469.16(C30H26O7,[M+H]+).Anal.Calcd for C30H26O7:C,72.28；H,5.26；O,22.47％；Found:72.21；H,5.24；O,22.56％.
实施例3：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-7-甲氧基-2H-苯并吡喃-2-酮(化合物3)的制备
制备方法同实施例1，区别在于以4-甲氧基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率69％，熔点137-139℃。1H NMR(600MHz,DMSO)δ8.59(s,1H),8.19(s,1H),8.02–7.95(m,2H),7.82(d,J＝8.7Hz,1H),7.68–7.61(m,2H),7.53(d,J＝8.7Hz,2H),7.33(d,J＝16.1Hz,1H),7.22(d,J＝8.7Hz,1H),7.08(d,J＝16.1Hz,1H),6.90(d,J＝8.7Hz,2H),3.88–3.84(m,9H),3.75(s,3H).13C NMR(151MHz,DMSO)δ190.16(s),164.61(s),164.02(s),162.26(s),161.96(s),158.88(s),152.32(s),149.44(s),145.20(s),141.83(s),135.02(s),132.49(s),131.35(s),129.19(s),129.10(s),127.59(s),124.77(s),121.57(s),120.34(s),117.23(s),116.79(s),113.47(s),106.40(s),100.21(s),59.63(s),59.35(s),59.07(s),58.25(s).MS(EI):469.17(C30H26O7,[M+H]+).Anal.Calcd forC30H26O7:C,72.28；H,5.26；O,22.47％；Found:C,72.31；H,5.25；O,22.45％.
实施例4：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-6-甲氧基-2H-苯并吡喃-2-酮(化合物4)的制备
制备方法同实施例1，区别在于以5-甲氧基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率65％，熔点123-124℃。1H NMR(600MHz,CDCl3)δ8.41(d,J＝5.2Hz,1H),8.24(d,J＝15.7Hz,1H),7.94–7.88(m,1H),7.52–7.48(m,2H),7.39(d,J＝16.0Hz,1H),7.27(dd,J＝7.0,4.9Hz,1H),7.20–7.17(m,1H),7.00(d,J＝2.9Hz,1H),6.92(t,J＝9.3Hz,1H),6.91–6.89(m,2H),6.71(d,J＝2.3Hz,1H),6.41(d,J＝2.3Hz,1H),3.92(s,3H),3.89(s,3H),3.85(s,3H),3.83(s,3H).13C NMR(151MHz,CDCl3)δ190.33(s),164.61(s),164.02(s),162.26(s),161.96(s),158.88(s),152.32(s),149.44(s),145.20(s),141.83(s),135.02(s),132.49(s),130.91(s),129.19(s),129.10(s),127.59(s),124.77(s),121.57(s),120.34(s),118.40(s),116.79(s),113.47(s),106.40(s),100.21(s),58.54(s),58.35(s),58.11(s),57.98(s).MS(EI):469.17(C30H26O7,[M+H]+).Anal.Calcd forC30H26O7:C,72.28；H,5.26；O,22.47％；Found:C,72.31；H,5.27；O,22.43％.
实施例5：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-5-甲氧基-2H-苯并吡喃-2-酮(化合物5)的制备
制备方法同实施例1，区别在于以6-甲氧基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率63％，熔点122-124℃。1H NMR(600MHz,CDCl3)δ8.92–8.88(m,1H),8.23(d,J＝15.7Hz,1H),7.92(d,J＝15.7Hz,1H),7.52(t,J＝5.4Hz,1H),7.52–7.49(m,2H),7.42(t,J＝10.9Hz,1H),6.96–6.91(m,2H),6.90(d,J＝8.7Hz,2H),6.72(t,J＝5.1Hz,2H),6.42(d,J＝2.3Hz,1H),3.95(s,3H),3.92(s,3H),3.90(s,3H),3.83(s,3H).13C NMR(151MHz,CDCl3)δ190.35(s),164.51(s),163.98(s),162.24(s),161.94(s),160.43(s),158.75(s),145.38(s),145.05(s),141.45(s),137.33(s),134.87(s),132.53(s),130.90(s),129.36(s),127.60(s),126.81(s),118.56(s),116.77(s),112.41(s),111.39(s),107.87(s),106.23(s),100.21(s),58.78(s),58.35(s),58.12(s),57.99(s).MS(EI):469.17(C30H26O7,[M+H]+).Anal.Calcd for C30H26O7:C,72.28；H,5.26；O,22.47％；Found:C,72.28；H,5.27；O,22.46％.
实施例6：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-8-甲基-2H-苯并吡喃-2-酮(化合物6)的制备
制备方法同实施例1，区别在于以3-甲基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率65％，熔点166-169℃。1H NMR(600MHz,CDCl3)δ8.47(d,J＝2.3Hz,1H),8.24(d,J＝15.7Hz,1H),7.94(d,J＝15.7Hz,1H),7.50(d,J＝8.7Hz,2H),7.45(dd,J＝10.0,7.3Hz,2H),7.39(t,J＝14.0Hz,1H),7.24–7.18(m,1H),6.96–6.88(m,3H),6.72(d,J＝2.2Hz,1H),6.42(d,J＝2.1Hz,1H),3.93(s,3H),3.89(s,3H),3.83(d,J＝1.6Hz,3H),2.47(s,3H).13C NMR(151MHz,CDCl3)δ190.38(s),164.58(s),164.03(s),162.26(s),161.97(s),156.13(s),150.13(s),145.22(s),141.77(s),137.69(s),135.01(s),132.53(s),130.90(s),130.15(s),129.15(s),128.81(s),127.57(s),126.99(s),121.04(s),118.43(s),116.79(s),106.36(s),100.24(s),58.35(s),58.11(s),57.98(s),18.08(s).MS(EI):483.17(C30H26O6,[M+H]+).Anal.Calcd for C30H26O6:C,74.67；H,5.43；O,19.89％；Found:C,74.63；H,5.43；O,19.93％.
实施例7：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-7-甲基-2H-苯并吡喃-2-酮(化合物7)的制备
制备方法同实施例1，区别在于以4-甲基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率70％，熔点155-159℃。1H NMR(600MHz,CDCl3)δ8.47(s,1H),8.25–8.21(m,1H),7.96–7.91(m,1H),7.49(dd,J＝8.2,5.7Hz,3H),7.42–7.38(m,1H),7.16–7.11(m,2H),6.93(d,J＝16.0Hz,1H),6.91–6.89(m,2H),6.71(d,J＝2.3Hz,1H),6.41(d,J＝2.3Hz,1H),3.92(s,3H),3.89(s,3H),3.83(s,3H),2.47(s,3H).13C NMR(151MHz,CDCl3)δ190.29(s),164.54(s),163.99(s),162.25(s),162.08(s),157.94(s),149.87(s),148.34(s),145.13(s),141.62(s),134.95(s),132.53(s),132.16(s),130.90(s),129.20(s),128.75(s),127.62(s),119.39(s),118.98(s),118.50(s),116.79(s),106.35(s),100.22(s),96.69(s),58.35(s),58.11(s),57.98(s),32.34(s).MS(EI):483.17(C30H26O6,[M+H]+).Anal.Calcd for C30H26O6:C,74.67；H,5.43；O,19.89％；Found:C,74.66；H,5.43；O,19.90％.
实施例8：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-6-甲基-2H-吡喃-2-酮(化合物8)的制备
制备方法同实施例1，区别在于以5-甲基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率61％，熔点143-146℃。1H NMR(600MHz,CDCl3)δ8.42(s,1H),8.24(d,J＝15.7Hz,1H),7.91(d,J＝15.7Hz,1H),7.50(d,J＝8.7Hz,2H),7.43–7.37(m,3H),7.24(d,J＝8.4Hz,1H),6.95–6.91(m,1H),6.90(d,J＝8.7Hz,2H),6.71(d,J＝2.3Hz,1H),6.41(d,J＝2.2Hz,1H),3.92(s,3H),3.89(s,3H),3.83(s,3H),2.41(s,3H).13C NMR(151MHz,CDCl3)δ190.35(s),164.59(s),164.00(s),162.26(s),162.01(s),155.91(s),149.68(s),145.17(s),141.76(s),137.56(s),137.20(s),134.99(s),132.51(s),132.04(s),130.90(s),129.14(s),128.84(s),127.61(s),121.05(s),118.97(s),116.79(s),106.38(s),100.21(s),96.69(s),58.35(s),58.11(s),57.98(s),23.36(s).MS(EI):483.17(C30H26O6,[M+H]+).Anal.Calcd for C30H26O6:C,74.67；H,5.43；O,19.89％；Found:C,74.61；H,5.44；O,19.94％.
实施例9：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-6-氟-2H-苯并吡喃-2-酮(化合物9)的制备
制备方法同实施例1，区别在于以5-氟水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率40％，熔点131-132℃。1H NMR(600MHz,CDCl3)δ8.38(s,1H),8.25(d,J＝15.7Hz,1H),7.87(d,J＝15.7Hz,1H),7.50(d,J＝8.6Hz,2H),7.38(d,J＝16.0Hz,1H),7.34–7.31(m,2H),6.95–6.89(m,3H),6.71(d,J＝2.2Hz,1H),6.42(d,J＝2.1Hz,1H),3.92(s,3H),3.90(s,3H),3.84(s,3H).13C NMR(151MHz,CDCl3)δ190.07(s),164.78(s),164.13(s),162.39(s),161.38(s),153.85(s),148.42(s),145.38(s),142.37(s),135.18(s),132.48(s),130.90(s),130.07(s),128.71(s),127.53(s),123.92(s),123.76(s),120.95(s),117.32(s),117.15(s),116.80(s),106.58(s),100.22(s),96.69(s),58.36(s),58.13(s),57.99(s).MS(EI):487.15(C29H23FO6,[M+H]+).Anal.Calcd for C29H23FO6:C,71.60；H,4.77；F,3.91；O,19.73％；Found:C,71.65；H,4.78；F,3.90；O,19.68％.
实施例10：7-氯-3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-2H-吡喃-2-酮(化合物10)的制备
制备方法同实施例1，区别在于以4-氯水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率42％，熔点159-161℃。1H NMR(600MHz,DMSO)δ8.57(s,1H),7.98(d,J＝15.9Hz,1H),7.90(d,J＝8.4Hz,1H),7.63(d,J＝1.2Hz,1H),7.48(ddd,J＝12.0,10.0,7.8Hz,4H),7.31(d,J＝16.1Hz,1H),7.06(d,J＝16.1Hz,1H),6.88(d,J＝8.6Hz,2H),6.81(d,J＝1.8Hz,1H),6.57(d,J＝1.7Hz,1H),3.91–3.81(m,6H),3.74(d,J＝16.9Hz,3H).13CNMR(151MHz,DMSO)δ190.57(s),165.05(s),164.06(s),162.41(s),161.10(s),157.80(s),148.85(s),144.77(s),141.77(s),141.39(s),135.49(s),134.69(s),132.44(s),131.33(s),129.59(s),128.90(s),128.36(s),127.18(s),120.52(s),119.43(s),117.50(s),117.21(s),107.19(s),100.85(s),59.06(s),58.65(s),58.26(s).MS(EI):503.15(C29H23ClO6,[M+H]+).Anal.Calcd for C29H23ClO6:C,69.25；H,4.61；Cl,7.05；O,19.09％；Found:C,69.31；H,4.60；Cl,7.00；O,19.09％.
实施例11：6-氯-3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-2H-吡喃-2-酮(化合物11)的制备
制备方法同实施例1，区别在于以5-氯水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率50％，熔点169-170℃。1H NMR(600MHz,CDCl3)δ8.36(s,1H),8.25(d,J＝15.7Hz,1H),7.86(d,J＝15.7Hz,1H),7.57(s,1H),7.54(dd,J＝8.8,1.5Hz,1H),7.50(d,J＝8.6Hz,2H),7.38(d,J＝15.9Hz,1H),7.29(d,J＝8.8Hz,1H),6.91(t,J＝12.9Hz,3H),6.71(s,1H),6.42(s,1H),3.92(s,3H),3.89(s,3H),3.84(s,3H).13C NMR(151MHz,CDCl3)δ189.90(s),164.78(s),164.11(s),162.34(s),161.23(s),155.98(s),148.08(s),145.45(s),142.44(s),136.17(s),135.20(s),132.69(s),132.42(s),131.29(s),130.90(s),128.64(s),127.51(s),122.38(s),120.71(s),118.38(s),116.81(s),106.51(s),100.22(s),96.69(s),58.36(s),58.13(s),57.99(s).MS(EI):503.12(C29H23ClO6,[M+H]+).Anal.Calcd for C29H23ClO6:C,69.25；H,4.61；Cl,7.05；O,19.09％；Found:C,69.26；H,4.60；Cl,7.07；O,19.06％.
实施例12：8-溴-3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-2H-吡喃-2-酮(化合物12)的制备
制备方法同实施例1，区别在于以3-溴水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率54％，熔点144-146℃。1H NMR(600MHz,CDCl3)δ8.43(s,1H),8.25(d,J＝15.7Hz,1H),7.93(d,J＝15.7Hz,1H),7.83(dd,J＝7.9,1.3Hz,1H),7.57(dd,J＝7.8,1.3Hz,1H),7.50(d,J＝8.6Hz,2H),7.39(d,J＝16.0Hz,1H),7.20(t,J＝7.8Hz,1H),6.96–6.89(m,3H),6.71(d,J＝2.3Hz,1H),6.42(d,J＝2.2Hz,1H),3.93(s,3H),3.90(s,3H),3.84(s,3H).13C NMR(151MHz,CDCl3)δ189.70(s),164.77(s),164.18(s),162.31(s),160.74(s),154.39(s),149.15(s),145.48(s),142.32(s),139.60(s),135.22(s),132.45(s),131.59(s),130.90(s),129.66(s),128.58(s),128.06(s),127.45(s),122.55(s),118.25(s),116.83(s),112.76(s),106.50(s),100.23(s),58.36(s),58.13(s),58.00(s).MS(EI):549.12(C29H23BrO6,[M+H]+).Anal.Calcd for C29H23BrO6:C,63.63；H,4.24；Br,14.60；O,17.54％；Found:C,63.60；H,4.25；Br,14.61；O,17.55％.
实施例13：7-溴-3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-2H-吡喃-2-酮(化合物13)的制备
制备方法同实施例1，区别在于以4-溴水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率54％，熔点144-146℃。1H NMR(600MHz,CDCl3)δ8.43(s,1H),8.25(d,J＝15.7Hz,1H),7.93(d,J＝15.7Hz,1H),7.83(dd,J＝7.9,1.3Hz,1H),7.57(dd,J＝7.8,1.3Hz,1H),7.50(d,J＝8.6Hz,2H),7.39(d,J＝16.0Hz,1H),7.20(t,J＝7.8Hz,1H),6.96–6.89(m,3H),6.71(d,J＝2.3Hz,1H),6.42(d,J＝2.2Hz,1H),3.93(s,3H),3.90(s,3H),3.84(s,3H).13C NMR(151MHz,CDCl3)δ189.70(s),164.77(s),164.18(s),162.31(s),160.74(s),154.39(s),149.15(s),145.48(s),142.32(s),139.60(s),135.22(s),132.45(s),131.59(s),130.90(s),129.66(s),128.58(s),128.06(s),127.45(s),122.55(s),118.25(s),116.83(s),112.76(s),106.50(s),100.23(s),58.36(s),58.13(s),58.00(s).MS(EI):549.12(C29H23BrO6,[M+H]+).Anal.Calcd for C29H23BrO6:C,63.63；H,4.24；Br,14.60；O,17.54％；Found:C,63.60；H,4.25；Br,14.61；O,17.55％.
实施例14：6-溴-3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-2H-吡喃-2-酮(化合物14)的制备
制备方法同实施例1，区别在于以5-溴水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率51％，熔点122-124℃。1H NMR(600MHz,CDCl3)δ8.35(s,1H),8.24(d,J＝15.7Hz,1H),7.85(d,J＝15.7Hz,1H),7.72(d,J＝2.2Hz,1H),7.67(dd,J＝8.8,2.3Hz,1H),7.49(d,J＝8.7Hz,2H),7.37(d,J＝16.0Hz,1H),7.23(d,J＝8.8Hz,1H),6.91(t,J＝12.8Hz,3H),6.71(d,J＝2.2Hz,1H),6.41(d,J＝2.2Hz,1H),3.92(s,3H),3.89(s,3H),3.83(s,3H).13C NMR(151MHz,CDCl3)δ189.73(s),164.78(s),164.11(s),162.31(s),161.07(s),156.44(s),147.98(s),145.39(s),142.41(s),138.95(s),135.19(s),134.36(s),132.41(s),130.90(s),130.00(s),128.62(s),127.49(s),122.77(s),120.98(s),119.92(s),118.24(s),116.80(s),106.50(s),100.21(s),58.36(s),58.13(s),57.99(s).MS(EI):549.14(C29H23BrO6,[M+H]+).Anal.Calcd for C29H23BrO6:C,63.63；H,4.24；Br,14.60；O,17.54％；Found:C,63.63；H,4.25；Br,14.60；O,17.53％.
实施例15：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-8-(甲氧基甲基)-2H-吡喃-2-酮(化合物15)的制备
制备方法同实施例1，区别在于以3-乙氧基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率68％，熔点125-128℃。1H NMR(600MHz,CDCl3)δ8.45(s,1H),8.24(d,J＝15.7Hz,1H),7.94(d,J＝15.7Hz,1H),7.50(d,J＝8.6Hz,2H),7.39(d,J＝16.0Hz,1H),7.20(d,J＝7.8Hz,1H),7.17(dd,J＝7.8,1.4Hz,1H),7.13(dd,J＝8.0,1.3Hz,1H),6.91(dd,J＝17.3,12.4Hz,3H),6.71(d,J＝1.8Hz,1H),6.41(d,J＝1.8Hz,1H),4.18(q,J＝7.0Hz,2H),3.92(s,3H),3.89(s,3H),3.83(s,3H),1.50(t,J＝7.0Hz,3H).13C NMR(151MHz,CDCl3)δ190.32(s),164.60(s),164.05(s),162.26(s),161.44(s),149.95(s),149.03(s),147.61(s),145.24(s),141.79(s),135.04(s),132.52(s),130.90(s),129.03(s),127.53(s),127.22(s),123.58(s),122.02(s),119.21(s),118.43(s),116.81(s),106.35(s),100.22(s),96.69(s),67.71(s),58.33(s),58.11(s),57.98(s),17.38(s).MS(EI):513.18(C31H28O7,[M+H]+).Anal.Calcd for C31H28O7:C,72.64；H,5.51；O,21.85％；Found:C,72.62；H,5.51；O,21.87％.
实施例16：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-7-(甲氧基甲基)-2H-吡喃-2-酮(化合物16)的制备
制备方法同实施例1，区别在于以4-乙氧基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率63％，熔点170-171℃。1H NMR(600MHz,CDCl3)δ8.49(s,1H),8.23(d,J＝15.7Hz,1H),7.98(d,J＝15.7Hz,1H),7.52–7.49(m,3H),7.40(dd,J＝12.3,6.8Hz,1H),6.93(d,J＝16.0Hz,1H),6.91–6.88(m,2H),6.79(d,J＝2.3Hz,1H),6.72(d,J＝2.3Hz,1H),6.64–6.62(m,1H),6.41(d,J＝2.3Hz,1H),4.12–4.10(m,2H),3.92(s,3H),3.89(s,3H),3.83(s,3H),3.79(d,J＝5.1Hz,2H).13C NMR(151MHz,CDCl3)δ190.12(s),166.84(s),164.43(s),163.92(s),162.26(d,J＝11.5Hz),160.12(s),150.30(s),144.99(s),141.24(s),134.84(s),133.69(s),132.57(s),130.91(s),130.13(s),129.40(s),127.69(s),118.62(s),116.77(s),116.50(d,J＝4.5Hz),114.96(s),106.28(s),103.36(s),100.21(s),96.69(s),67.12(s),58.35(s),58.10(s),57.97(s),32.34(s).MS(EI):513.24(C31H28O7,[M+H]+).Anal.Calcd for C31H28O7:C,72.64；H,5.51；O,21.85％；Found:C,72.66；H,5.52；O,21.82％.
实施例17：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-5,7-二甲氧基-2H-苯并吡喃-2-酮(化合物17)的制备
制备方法同实施例1，区别在于以4,6-二甲氧基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率73％，熔点142-143℃。1H NMR(600MHz,CDCl3)δ8.84(s,1H),8.21(d,J＝15.7Hz,1H),7.98(d,J＝15.7Hz,1H),7.50(d,J＝8.7Hz,2H),7.41(d,J＝16.0Hz,1H),6.93(d,J＝16.0Hz,1H),6.89(d,J＝8.7Hz,2H),6.71(d,J＝2.3Hz,1H),6.40(dd,J＝10.8,2.1Hz,2H),6.25(t,J＝3.0Hz,1H),3.91(s,3H),3.89(s,3H),3.88(s,3H),3.86(s,3H),3.82(s,3H).13C NMR(151MHz,CDCl3)δ190.14(s),168.69(s),164.29(s),163.83(s),162.48(s),162.18(s),161.47(s),160.92(s),146.04(s),144.81(s),140.81(s),134.68(s),132.60(s),130.89(s),130.07(s),129.70(s),127.70(s),122.76(s),118.73(s),116.75(s),116.33(s),107.11(s),106.15(s),100.21(s),97.63(s),95.17(s),58.73(s),58.65(s),58.33(s),58.08(s),57.97(s).MS(EI):529.24(C31H28O8,[M+H]+).Anal.Calcdfor C31H28O8:C,70.44；H,5.34；O,24.22％；Found:C,70.47；H,5.32；O,24.21％.
实施例18：6-溴-3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-8-甲氧基-2H-苯并吡喃-2-酮(化合物18)的制备
制备方法同实施例1，区别在于以5-溴-3-甲氧基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率60％，熔点133-134℃。1H NMR(600MHz,CDCl3)δ8.32(s,1H),8.23(d,J＝15.7Hz,1H),7.88(d,J＝15.7Hz,1H),7.49(d,J＝8.7Hz,2H),7.37(d,J＝16.0Hz,1H),7.31(d,J＝1.9Hz,1H),7.21(d,J＝1.9Hz,1H),6.91(t,J＝11.4Hz,3H),6.70(d,J＝2.2Hz,1H),6.41(d,J＝2.1Hz,1H),3.96(s,3H),3.91(s,3H),3.89(s,3H),3.84(s,3H).13CNMR(151MHz,CDCl3)δ189.83(s),164.74(s),164.12(s),162.37(s),160.59(s),150.51(s),148.28(s),146.49(s),145.40(s),142.35(s),135.20(s),132.43(s),130.89(s),130.24(s),128.64(s),127.46(s),125.44(s),122.82(s),120.92(s),119.57(s),118.27(s),116.82(s),106.46(s),100.20(s),59.22(s),58.33(s),58.12(s),57.99(s).MS(EI):577.04(C30H25BrO7,[M+H]+).Anal.Calcd for C30H25BrO7:C,62.40；H,4.36；Br,13.84；O,19.40％；Found:C,62.42；H,4.35；Br,13.84；O,19.39％.
实施例19：6-烯丙基-3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-8-甲氧基-2H-苯并吡喃-2-酮(化合物19)的制备
制备方法同实施例1，区别在于以5-烯丙基-3-甲氧基水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率53％，熔点161-163℃。1H NMR(600MHz,CDCl3)δ8.40(s,1H),8.23(d,J＝15.7Hz,1H),7.92(d,J＝15.7Hz,1H),7.49(d,J＝8.7Hz,2H),7.39(d,J＝16.0Hz,1H),6.97(dd,J＝10.2,3.1Hz,2H),6.92(d,J＝16.1Hz,1H),6.89(d,J＝8.7Hz,2H),6.70(d,J＝2.3Hz,1H),6.40(d,J＝2.2Hz,1H),5.94(ddt,J＝16.8,10.1,6.7Hz,1H),5.16–5.09(m,2H),3.94(s,3H),3.90(s,3H),3.88(s,3H),3.83(s,3H),3.42(d,J＝6.7Hz,2H).13C NMR(151MHz,CDCl3)δ190.31(s),164.56(s),164.01(s),162.23(s),161.38(s),149.89(s),149.53(s),146.03(s),145.19(s),141.74(s),139.46(s),138.95(s),135.01(s),132.50(s),130.90(s),129.13(s),129.07(s),127.55(s),122.89(s),121.68(s),119.57(s),118.74(s),118.44(s),116.79(s),106.31(s),100.19(s),58.93(s),58.32(s),58.11(s),57.98(s),42.37(s).MS(EI):539.24(C33H30O7,[M+H]+).Anal.Calcd forC33H30O7:C,73.59；H,5.61；O,20.79％；Found:C,73.55；H,5.63；O,20.81％.
实施例20：3-((E)-3-(2,4-二甲氧基-6-(4-甲氧苯乙烯基)苯基)丙烯酰基)-7-(二甲基氨基)-2H-吡喃-2-酮(化合物20)的制备
制备方法同实施例1，区别在于以4-(二甲氨基)水杨醛代替水杨醛，得到黄色固体粉末目标化合物，收率54％，熔点154-155℃。1H NMR(600MHz,CDCl3)δ8.47(s,1H),8.20(d,J＝15.7Hz,1H),8.10–8.05(m,1H),7.53–7.49(m,2H),7.44–7.41(m,1H),7.40–7.38(m,1H),6.94(d,J＝16.0Hz,1H),6.91–6.88(m,2H),6.72(d,J＝2.4Hz,1H),6.61(dd,J＝8.9,2.4Hz,1H),6.44(d,J＝2.4Hz,1H),6.41(d,J＝2.3Hz,1H),3.91(s,3H),3.88(d,J＝4.9Hz,3H),3.83–3.81(m,3H),3.09–3.08(m,7H).13C NMR(151MHz,CDCl3)δ190.16(s),164.11(s),163.74(s),162.14(s),160.72(s),157.22(s),150.83(s),144.62(s),140.15(s),134.53(s),133.88(s),132.68(s),130.90(s),130.22(s),127.86(s),120.99(s),119.00(s),116.75(s),116.42(s),112.44(s),111.53(s),106.07(s),100.21(s),99.72(s),58.33(s),58.07(s),57.97(s),42.88(s),32.34(s).MS(EI):512.20(C31H29NO6,[M+H]+).Anal.Calcd for C31H29NO6:C,72.78；H,5.71；N,2.74；O,18.77％；Found:C,72.79；H,5.71；N,2.74；O,18.76％.
实施例21：二苯乙烯香豆素类衍生物(化合物1-20)对单胺氧化酶的抑制活性评价
先配制含有待测化合物的0.1mL的磷酸钠缓冲液(0.05M,pH 7.4)，再将重组hMAO-A或hMAO-B调节到这两种亚型具有相同的反应浓度：165pmol的对酪胺/分钟(hMAO-A:1.1μg蛋白；比活性:150nmol的对酪胺氧化羟基苯乙醛/min/mg蛋白；hMAO-B:7.5μg蛋白；比活性:22nmol的对酪胺转化/min/mg蛋白)。这些混合物在37℃黑暗荧光室中放置15min。之后，加入200μM的ADHP试剂、1U/mL辣根过氧化物酶和1mM对酪胺。在37℃条件下，通过酶标仪检测OD590值，计算IC50值，结果见表1所示：
表1.化合物对MAO-A和MAO-B的IC50值
从表1中可以看出，化合物7对hMAO-B显示出较好的抑制活性，其IC50值是2.78±0.11μM。化合物7相比于对照组司来吉兰(Selegiline)的IC50＝2.89±0.05μM而言，其对hMAO-A和hMAO-B的选择性SI＝20.9，也同对照组类似。化合物1-20中，发现在化合物3-位和4-位具有甲基、甲氧基和溴等基团的化合物，其对hMAO-B有着能够同对照近似的抑制活性，其选择性也类似，如化合物3、7、13和15。所以，推测该主体结构在3-和4-位上引入基团能够提高化合物对hMAO-B的抑制活性及选择性。
以上显示和描述了本发明的基本原理和主要特征和本发明的优点。本行业的技术人员应该了解，本发明不受上述实施例的限制，上述实施例和说明书中描述的只是说明本发明的原理，在不脱离本发明精神和范围的前提下，本发明还会有各种变化和改进，这些变化和改进都落入要求保护的本发明范围内。本发明要求保护范围由所附的权利要求书及其等效物界定。

Claims (6)

1.一类二苯乙烯香豆素类衍生物，其特征在于：所述二苯乙烯香豆素类衍生物选自如下结构：
2.一种权利要求1所述的二苯乙烯香豆素类衍生物的制备方法，其特征在于按如下步骤操作：
(1)先向N,N-二甲基甲酰胺中加入白藜芦醇三甲醚，然后于冰浴中缓慢滴加三氯氧磷，滴加完毕后恢复至室温反应，1h后停止反应，随后将反应液逐滴加入到冰水与乙酸乙酯的混合溶液中，再分次加入碳酸钠固体直至无气泡产生，搅拌过夜后析出淡黄色固体，抽滤、干燥，最后柱层析分离得到化合物A；所述化合物A的结构式如下所示：
(2)先向乙酰乙酸乙酯中加入取代水杨醛，再加入哌啶，搅拌5min后加入无水乙醇，继续搅拌反应直至不再产生沉淀，随后对反应液抽滤，然后先用石油醚洗涤，再用乙醇洗涤，最后干燥后得到化合物B；所述化合物B的结构式如下所示：
所述取代水杨醛选自水杨醛、3-甲氧基水杨醛、4-甲氧基水杨醛、6-甲氧基水杨醛、3-甲基水杨醛、4-甲基水杨醛、5-甲基水杨醛、5-氟水杨醛、4-氯水杨醛、4-溴水杨醛、5-溴水杨醛、3-乙氧基水杨醛、4-乙氧基水杨醛、4,6-二甲氧基水杨醛、5-烯丙基-3-甲氧基水杨醛；
(3)向无水乙醇中加入化合物A和化合物B，所得混合液于45℃水浴条件搅拌反应5min，再加入哌啶，反应24h后停止反应，抽滤、干燥，最后柱层析分离得到目标产物。
3.根据权利要求2所述的二苯乙烯香豆素类衍生物的制备方法，其特征在于：步骤(1)中所述白藜芦醇三甲醚与所述三氯氧磷的摩尔比为1:1，冰水与乙酸乙酯的体积比为5:1，N,N-二甲基甲酰胺的用量为每毫摩尔白藜芦醇三甲醚用0.5mL。
4.根据权利要求2所述的二苯乙烯香豆素类衍生物的制备方法，其特征在于：步骤(2)中所述乙酰乙酸乙酯与所述取代水杨醛的摩尔比为1:1，哌啶的用量为每毫摩尔乙酰乙酸乙酯用0.05mL，无水乙醇的用量为每毫摩尔取代水杨醛用1mL。
5.根据权利要求2所述的二苯乙烯香豆素类衍生物的制备方法，其特征在于：步骤(3)中所述化合物A与所述化合物B的摩尔比为1.5:1，哌啶的用量为每毫摩尔化合物B用0.05mL，无水乙醇的用量为每毫摩尔化合物B用10mL。
6.如权利要求1所述的二苯乙烯香豆素类衍生物在制备单胺氧化酶抑制剂中的应用。
CN201510290010.8A 2015-05-29 2015-05-29 一类二苯乙烯香豆素类衍生物及其制备方法与用途 Active CN104892556B (zh)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510290010.8A CN104892556B (zh) 2015-05-29 2015-05-29 一类二苯乙烯香豆素类衍生物及其制备方法与用途

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510290010.8A CN104892556B (zh) 2015-05-29 2015-05-29 一类二苯乙烯香豆素类衍生物及其制备方法与用途

Publications (2)

Publication Number Publication Date
CN104892556A CN104892556A (zh) 2015-09-09
CN104892556B true CN104892556B (zh) 2017-01-04

Family

ID=54025570

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510290010.8A Active CN104892556B (zh) 2015-05-29 2015-05-29 一类二苯乙烯香豆素类衍生物及其制备方法与用途

Country Status (1)

Country Link
CN (1) CN104892556B (zh)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107936172B (zh) * 2018-01-08 2023-04-28 无锡佶达德光电子技术有限公司 一种香豆素类聚合物半导体激光材料的制备方法
CN108558813B (zh) * 2018-03-30 2021-07-23 合肥工业大学 一种含有类黄酮的白藜芦醇类衍生物及其制备方法和用途
CN109761964B (zh) * 2018-12-29 2021-02-02 浙江工业大学 香豆素骈3-羟基吡啶-4-酮的衍生物及其制备方法与应用

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN100469841C (zh) * 2005-12-27 2009-03-18 中国科学院理化技术研究所 以二苯乙烯连接的香豆素类染料及其合成方法和用途
CN101759815B (zh) * 2008-12-25 2011-12-28 中国科学院理化技术研究所 香豆素和/或苄叉环烷烃酮染料在制备双光子聚合树脂中的应用
CN102389416B (zh) * 2011-10-10 2013-09-04 山西医科大学 杜鹃素与其衍生物及其可药用盐在制备由血管收缩引起的心脑血管疾病药物中的应用

Also Published As

Publication number Publication date
CN104892556A (zh) 2015-09-09

Similar Documents

Publication Publication Date Title
CN104892556B (zh) 一类二苯乙烯香豆素类衍生物及其制备方法与用途
Rayanil et al. A new phenolic compound with anticancer activity from the wood of Millettia leucantha
Lewin et al. Semisynthesis of natural flavones inhibiting tubulin polymerization, from hesperidin
JP2002523410A (ja) シクロオキシゲナーゼ−２阻害剤としてのジアリールベンゾピラン誘導体
Cordes et al. Total syntheses of angelicoin A, hericenone J, and hericenol A via migratory prenyl-and geranylation–aromatization sequences
Al-Maharik et al. Synthesis of lupiwighteone via a para-Claisen–Cope rearrangement
Naik et al. Molecular iodine catalyst promoted synthesis of chromans and 4-aryl-3, 4-dihydrobenzopyran-2-ones via [3+ 3] cyclocoupling
Sasaki et al. Prenylated flavonoids from the stems and leaves of Desmodium caudatum and evaluation of their inhibitory activity against the film-forming growth of Zygosaccharomyces rouxii F51
Cardinal et al. Total synthesis of quebecol
Hodgetts et al. Conjugate addition to 3-arylsulfinylchromones as a synthetic route to homochiral 2-substituted chromanones: scope and limitations
CN107382998A (zh) 一种含氟香豆素噻唑类化合物及其合成方法
Zambare et al. Development of mild and efficient method for synthesis of substituted flavones using oxalic acid catalyst
Nagarathnam et al. A practical synthesis of flavones from methyl salicylate
Bennett et al. Synthesis of minor xanthones from Garcinia mangostana
CN105085458B (zh) 一种香豆素类衍生物的合成方法
CN107417532A (zh) 一种白藜芦醇丙烯酸酚酯类衍生物及其制备方法和用途
CN107868063B (zh) 一种四氢苯并噻唑-2-丙酮肟衍生物及其制备方法和应用
Esteves et al. Synthesis of Novel 1-Aryl-9H-xanthen-9-ones
CN106565734B (zh) 一种补骨脂素酯类衍生物及用途
Rocha et al. One-pot synthesis of 3-Methylflavones and their transformation into (E)-3-Styrylflavones via Wittig reactions
CN105111054B (zh) 一种共轭体系增大的姜黄素类似物及其制备方法和应用
CN104693213B (zh) 黄酮类天然化合物Frutinones A、B和C的合成方法
CN108558813A (zh) 一种含有类黄酮的白藜芦醇类衍生物及其制备方法和用途
Alizadeh et al. Synthesis of some novel pyrano [2, 3-f] chromenone derivatives
CN106928176B (zh) 一种含香豆素的1,4-戊二烯-3-酮类衍生物及其制备方法和用途

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
TR01 Transfer of patent right

Effective date of registration: 20201228

Address after: 245000 No. 50, Meilin Avenue, Huangshan Economic Development Zone, Anhui Province

Patentee after: Huangshan Development Investment Group Co.,Ltd.

Address before: Tunxi road in Baohe District of Hefei city of Anhui Province, No. 193 230009

Patentee before: Hefei University of Technology

TR01 Transfer of patent right