CN1331841C - 一类白藜芦醇的衍生物及其制法和用途 - Google Patents
一类白藜芦醇的衍生物及其制法和用途 Download PDFInfo
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Abstract
一类白藜芦醇的衍生物,它具有如下通式:式Ⅰ中R1为氢或者甲基;R2为CH2NHR3或CH=NR3,其中R3为环丙基、环丁基、环戊基或环己基,或者R3为具有如下结构的基团(化学式A和B):式B中的X为氟、氯、溴、碘或羟基。实验表明,本发明的白藜芦醇的衍生物对S180、EAC和HepA细胞显示细胞毒性,对鼻咽癌、乳腺癌、肝癌、肺癌和大肠癌均有明显的抑制作用,因此本发明的白藜芦醇衍生物可以用于制备抗肿瘤药物。本发明公开了其制法。
Description
技术领域
本发明涉及一类具有多种抗癌功能的新型白藜芦醇的衍生物及其制法和用途。
技术背景
白藜芦醇(Resveratrol,3,5,4′-三羟基二苯乙烯)是一类具有多羟基的酚类化合物,它具有顺反两种结构,在自然界中以反式结构为主。白藜芦醇存在于虎杖、桑葚、花生、葡萄等70多种植物中,具有多种生理活性:抗血小板凝集、抑制心血管疾病的发生、保护肝脏、抗氧化等。然而,直到20世纪90年代科学家发现白藜芦醇对癌变过程中细胞和组织变异的三个主要阶段(诱导、起始和发展)都有抑制作用,成为抑制和治疗组织癌变和肿瘤发生最有前途的药物之一后,白藜芦醇才引起了药物学家的广泛关注。
研究发现,白藜芦醇本身并不能应用于临床,必须对其结构进行一定的修饰才有可能成为优良的临床抗癌药物。目前,仅有极少的白藜芦醇衍生物作为抗癌药物进入临床试验阶段,且均为全合成的化合物。以天然产物中的活性成分为母体化合物,根据药物化学的基本原理,设计出可能具有高活性、高选择性及低毒副作用的半合成化合物,从而发现可能应用于临床的新化合物是目前新药开发的一种重要手段。
发明内容
本发明的目的在于提供一类新的白藜芦醇的衍生物以及它们的制法和用途。
本发明的技术方案如下:
一类白藜芦醇的衍生物,它具有如下通式:
式I中R1为氢(H)或者甲基(CH3);R2为CH2NHR3、CHO或CH=NR3,R3为环丙基、环丁基、环戊基或环己基,或者为具有如下结构的基团(化学式A和B):
式B中的X为氟(F)、氯(Cl)、溴(Br)、碘(I)、或羟基(OH)。
一种制备上述白藜芦醇的衍生物的方法,它是将3,5,4′-三甲氧基二苯乙烯(化合物C)溶于无水DMF中,冰浴及搅拌下慢慢滴加SOCl2或者POCl3,3,5,4′-三甲氧基二苯乙烯与SOCl2或者POCl3的物质的量之比为1∶1~1∶0.1,得到下式表示的白藜芦醇衍生物(化合物D):
一种制备上述白藜芦醇的衍生物的方法,它是将上述方法制得的化合物D溶于无水乙醇中,慢慢滴加R3NH2的伯胺类化合物(物质的量之比为化合物D:R3NH2=1∶1~1∶1.2),常温下搅拌4小时,即得到如式II化合物的白藜芦醇衍生物:
式II中R1=CH3,R3为环丙基、环丁基、环戊基或环己基,或者R3为具有如下结构的基团(化学式A和B):
式B中的X为氟(F)、氯(Cl)、溴(Br)、碘(I)、或羟基(OH)。
一种制备上述白藜芦醇的衍生物的方法,它是将上述方法制得的产物式II化合物与BBr3在二氯甲烷中反应,物质的量之比为:式II化合物∶BBr3=1∶1~1∶1.5,即得到结构式如式II的化合物,但式中R1= H,R3仍为环丙基、环丁:基、环戊基或环己基,或者R3为具有如下结构的基团(化学式A和B):
式B中的X为氟(F)、氯(Cl)、溴(Br)、碘(I)、或羟基(OH)。
一种制备上述白藜芦醇的衍生物的方法,它是将上述方法制得的产物式II化合物溶于无水乙醇中,分批加入NaBH4(物质的量之比为:式II化合物∶NaBH4=1∷0.5~1∷1.5),常温下搅拌2小时,即得到结构式如式III的白藜芦醇衍生物:
式III中R1=CH3,R3=环丙基、环丁基、环戊基或环己基,或者R3为具有如下结构的基团(化学式A和B):
一种制备上述白藜芦醇的衍生物的方法,它是将上述方法制得的产物式III化合物与BBr3在二氯甲烷中反应(物质的量之比为:式III化合物∶BBr3=1∶1~1∶1.5),即得到结构式如式III的白藜芦醇衍生物,但式中R1=H,R3仍为环丙基、环丁基、环戊基或环己基,或者R3为具有如下结构的基团(化学式A和B):
实验表明,本发明的白藜芦醇的衍生物对S180、EAC和HepA细胞显示细胞毒性,对鼻咽癌、乳腺癌、肝癌、肺癌和大肠癌均有明显的抑制作用,因此本发明的白藜芦醇衍生物可以用于制备抗肿瘤药物。
具体实施方式
通过以下实施例进一步详细说明本发明,但应注意本发明的范围并不受这些实施例的任何限制。
实施例1:3,5,4′-三甲氧基二苯乙烯的制备
白藜芦醇(22.8g,0.1mol),溶解在100ml的10%NaOH溶液中,搅拌下在N2保护及冰浴条件下慢慢滴加37.9ml硫酸二甲酯(0.4mol),控制滴速使反应体系温度不超过40℃,反应2小时后滤出生成的白色固体,石油醚-乙酸乙酯(9∶1)中重结晶即得到无色针状结晶,产率92%。Mp 52-54℃;ESI-MS:270.1249(calc.270.1255);1HNMR(DMSO-d6)δppm:3.77(s,9H,3×OCH3),6.39(t,1H,C4-H),6.74(d,2H,C2,6-H),7.01(d,1H,C7-H),7.20(d,1H,C8-H),6.94(d,2H,C3′,5′-H),7.53(d,2H,C2′,6′-H)。
实施例2:2-甲酰基-3,5,4′-三甲氧基二苯乙烯的制备
将实施例1中得到的3,5,4′-三甲氧基二苯乙烯27.0g(0.1mol),溶解在50ml无水DMF中,在冰浴条件下边搅拌边滴加15.3g(0.1mol)POCl3,15min之内滴加完毕。反应产物慢慢倾入400ml冰水混合物中,静置过夜,滤出固体,丙酮重结晶,得到无色针状结晶,产率84%。Mp 63-65℃;ESI-MS:298.1209(calc.298.1205);IR(KBr)cm-1:1705(CO);1H NMR(DMSO-d6)δppm:3.78(s,3H,C4′-OCH3),3.90(s,3H,C3-OCH3),3.92(s,3H,C5-OCH3),6.62(t,1H,C4-H),6.91(t,1H,C6-H),6.97(d,2H,C3′,5′-H),7.50(d,2H,C2′,6′-H),7.21(d,1H,C7-H),7.95(d,1H,C8-H)。
实施例3:N-环戊基-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺的制备
将实施例2中得到的2-甲酰基-3,5,4′-三甲氧基二苯乙烯29.8g(0.1mol)及环戊胺8.5g(0.1mol)溶解在100ml无水乙醇中,常温下搅拌2小时后,减压蒸去部分无水乙醇,重结晶,得到无色针状结晶,产率94%。Mp 76-78℃;ESI-MS:365.1986(calc.365.1990);IR(KBr)cm-1:1680(C=N);1H NMR(DMSO-d6)δppm:1.63(m,4H,CH2CH2),1.82(m,4H,CH2CH),3.72(t,1H,CH),3.77(s,3H,C4′-OCH3),3.84(s,3H,C3-OCH3),3.86(s,3H,C5-OCH3),6.53(d,1H,C4-H),6.91(d,1H,C6-H),6.94(d,2H,C3′,5′-H),7.43(d,2H,C2′,6′-H),7.10(d,1H,C7-H),8.08(d,1H,C8-H),8.61(s,1H,CH=N)。
实施例4:N-环戊基-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺的制备
将实施例3中得到的N-环戊基-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺36.5g(0.1mol)溶解在40ml无水二氯甲烷中,常温下边搅拌边滴加75.2g(0.3mol)BBr3的无水二氯甲烷溶液,反应4小时后,产物分别用饱和氯化钠水溶液及蒸馏水各洗涤三次,再用无水硫酸钠干燥二氯甲烷部分,减压回收得到白色固体,产率94%。Mp 96-98℃;ESI-MS:323.1528(calc.323.1521);IR(KBr)cm-1:1680(C=N),3610(OH);1H NMR(DMSO-d6)δppm:1.63(m,4H,CH2CH2),1.82(m,4H,CH2CH),2.73(t,1H,CH),6.63(d,1H,C4-H),6.94(d,1H,C6-H),6.73(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.11(d,1H,C8-H),8.61(s,1H,CH=N),9.12(s,1H,C4′-OH),9.43(s,2H,C3,5-OH)。
实施例5:N-环戊基-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺的制备
将实施例3中得到的N-环戊基-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺73.0g(0.2mol)溶解在50ml无水乙醇中,40℃下边搅拌边30分钟内分批加完3.8g(0.1mol)NaBH4,反应2小时后,减压蒸干产物,二氯甲烷溶解后用饱和氯化钠水溶液及蒸馏水各洗涤三次,再用无水硫酸钠干燥二氯甲烷部分,减压回收得到白色固体,产率96%。Mp 72-74℃;ESI-MS:367.2152(calc.367.2147);IR(KBr)cm-1:1180(C-N),3320(NH);1H NMR(DMSO-d6)δppm:1.63(m,4H,CH2CH2),1.83(m,4H,CH2CH),2.72(t,1H,CH),3.75(s,3H,C4′-OCH3),3.77(s,3H,C3-OCH3),3.78(s,3H,C5-OCH3),3.80(s,2H,CH2NH),6.52(d,1H,C4-H),6.93(d,1H,C6-H),6.92(d,2H,C3′,5′-H),7.44(d,2H,C2′,6′-H),7.10(d,1H,C7-H),8.08(d,1H,C8-H)。
实施例6:N-环戊基-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺的制备
将实施例5中得到的N-环戊基-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺的36.7g(0.1mol)溶解在40ml无水二氯甲烷中,常温下边搅拌边滴加75.2g(0.3mol)BBr3的无水二氯甲烷溶液,反应4小时后,产物分别用饱和氯化钠水溶液及蒸馏水各洗涤三次,再用无水硫酸钠干燥二氯甲烷部分,减压回收得到白色固体,产率94%。Mp 81-83℃;ESI-MS:325.1681(calc.325.1677);IR(KBr)cm-1:1175(C-N),3310(NH),3620(OH);1H NMR(DMSO-d6)δppm:1.62(m,4H,CH2CH2),1.83(m,4H,CH2CH),2.72(t,1H,CH),3.80(s,2H,CH2NH),6.63(d,1H,C4-H),6.94(d,1H,C6-H),6.73(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.11(d,1H,C8-H),9.12(s,1H,C4′-OH),9.43(s,2H,C3,5-OH)。
实施例7:N-(4-羟基-苯乙基)-3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺的制备
将实施例2中得到的2-甲酰基-3,5,4′-三甲氧基二苯乙烯29.8g(0.1mol)及酪胺13.7g(0.1mol)溶解在100ml无水乙醇中,常温下搅拌2小时后,减压蒸去部分无水乙醇,重结晶,得到无色针状结晶,产率94%。Mp 125-127℃;ESI-MS:417.1942(calc.417.1940);IR(KBr)cm-1:1680(C=N),3610(OH);1HNMR(DMSO-d6)δppm:2.74(t,2H,ArCH2),2.98(t,2H,CH2N),3.75(s,3H,C4′-OCH3),3.77(s,3H,C3-OCH3),3.78(s,3H,C5-OCH3),6.47(d,1H,C4-H),6.81(d,1H,C6-H),6.63(d,2H,C3′,5′-H),7.52(d,2H,C2′,6′-H),7.10(d,1H,C7-H),7.34(d,1H,C8-H),6.95(m,4H,ArH),8.61(s,1H,CH=N),9.15(s,1H,Ar-OH)。
实施例8:N-(4-羟基-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺的制备
将实施例7中得到的N-(4-羟基-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺41.8g(0.1mol)溶解在100ml无水二氯甲烷中,常温下边搅拌边滴加75.2g(0.3mol)BBr3的无水二氯甲烷溶液,反应4小时后,产物分别用饱和氯化钠水溶液及蒸馏水各洗涤三次,再用无水硫酸钠干燥二氯甲烷部分,减压回收得到白色固体,产率94%。Mp 154-156℃;ESI-MS:375.1468(calc.375.1470);IR(KBr)cm-1:1680(C=N),3610(OH);1H NMR(DMSO-d6)δppm:2.74(t,2H,ArCH2),2.98(t,2H,CH2N),6.46(d,1H,C4-H),6.82(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),6.95(m,4H,ArH),8.61(s,1H,CH=N),9.15(s,1H,Ar-OH),9.12(s,1H,C4′-OH),9.43(s,2H,C3,5-OH)。
实施例9:N-(4-羟基-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺的制备
将实施例7中得到的N-(4-羟基-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺83.6g(0.2mol)溶解在50ml无水乙醇中,40℃下边搅拌边30分钟内分批加完3.8g(0.1mol)NaBH4,反应2小时后,减压蒸干产物,二氯甲烷溶解后用饱和氯化钠水溶液及蒸馏水各洗涤三次,再用无水硫酸钠干燥二氯甲烷部分,减压回收得到白色固体,产率96%。Mp 115-117℃;ESI-MS:419.2099(calc.419.2096);IR(KBr)cm-1:1175(C-N),3310(NH),3622(OH);1H NMR(DMSO-d6)δppm:2.64(t,2H,ArCH2),2.79(t,2H,CH2NH),3.75(s,3H,C4′-OCH3),3.77(s,3H,C3-OCH3),3.78(s,3H,C5-OCH3),3.80(s,2H,CH2NH),6.47(d,1H,C4-H),6.81(d,1H,C6-H),6.63(d,2H,C3′,5′-H),7.52(d,2H,C2′,6′-H),7.10(d,1H,C7-H),7.34(d,1H,C8-H),6.95(m,4H,ArH),9.15(s,1H,Ar-OH)。
实施例10:N-(4-羟基-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺的制备
将实施例9中得到的N-(4-羟基-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺42.0g(0.1mol)溶解在100ml无水二氯甲烷中,常温下边搅拌边滴加75.2g(0.3mol)BBr3的无水二氯甲烷溶液,反应4小时后,产物分别用饱和氯化钠水溶液及蒸馏水各洗涤三次,再用无水硫酸钠干燥二氯甲烷部分,减压回收得到白色固体,产率94%。Mp 130-132℃;ESI-MS:377.1624(calc.377.1627);IR(KBr)cm-1:1175(C-N),3310(NH),3618(OH);1H NMR(DMSO-d6)δppm:2.64(t,2H,ArCH2),2.79(t,2H,CH2NH),3.80(s,2H,CH2NH),6.46(d,1H,C4-H),6.82(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),6.95(m,4H,ArH),9.1 5(s,1H,Ar-OH),9.12(s,1H,C4′-OH),9.43(s,2H,C3,5-OH)。
实施例11:
按上述相似的方法制备了表1中所列的白藜芦醇的衍生物。
表1.本发明的白藜芦醇衍生物通式II中R基团所代表的取代基
续表1.本发明的白藜芦醇衍生物通式III中R基团所代表的取代基
实施例12:白藜芦醇及其主要衍生物对S180,EAC,HepA的细胞毒作用
方法:MTT法。取对数生长的S180,EAC和HepA的细胞,分别稀释成2×104个/ml,分装于96孔板(0.2ml/孔)。设5-氟尿嘧啶对照组,DMSO对照组及8个不同浓度的受测化合物,每孔10μl。各组设4个平行孔,置37℃,5%CO2中培养72h实验终止前4h打入MTT液(5mg/ml)10μl/孔,再培养4h。弃去培养液,加入DMSO 100μl/孔,混匀振荡,在570nm波长下,用美国生产的BioRad 550型酶标仪测出OD值,按下列公式计算出细胞生长抑制率(半数抑制浓度,IC50)。
生长抑制率=(1-用药组平均OD值/对照组平均OD值)×100%IC50越小,此化合物的细胞毒性越大,结果见表2。
表2白藜芦醇及其主要衍生物对S180,EAC和HcpA的细胞毒性(IC50)
细胞株 | 化合物号/IC50(μg/ml) | |||||||
1 | 5 | 6 | 7 | 12 | 15 | 白藜芦醇 | 5-氟尿嘧啶 | |
S180 | 4.24 | 24 | 21.34 | 16 | 0.28 | 4.36 | 34 | 1.32 |
EAC | 10.26 | 41 | 0.22 | 45 | 3.42 | 23 | 63 | 0.26 |
HepA | 2.36 | 8.28 | 2.14 | 1.29 | 2.53 | 12 | 56 | 1.87 |
结果表明:本发明所述主要白藜芦醇衍生物均对S180,EAC和HepA细胞显示出比白藜芦醇强的细胞毒性,大部分与阳性对照5-氟尿嘧啶相当,其中,化合物12对S180细胞、化合物6对EAC细胞、化合物7对HepA细胞的细胞毒性甚至比5-氟尿嘧啶的还要强。
实施例13:白藜芦醇及其主要衍生物对5种人癌细胞的抑制作用
方法:MTT法。实验方法同实施例12,结果见表3。
表3.白藜芦醇及其主要衍生物对5种人癌细胞的抑制作用
组别 | 药物浓度(μg/ml) | 抑制率(%) | ||||
鼻咽癌(CNE2) | 乳腺癌(MCF-7) | 肝癌(Bel-7402) | 肺癌(GLC-82) | 大肠癌(HT-29) | ||
化合物4 | 0.8 | 29.8 | 32.1 | 45.2 | 26.6 | 18.9 |
1.4 | 62.3 | 56.8 | 68.7 | 55.2 | 45.9 | |
2.0 | 95.2 | 85.4 | 91.3 | 82.4 | 88.2 | |
化合物10 | 0.8 | 19.4 | 22.1 | 33.2 | 45.7 | 31.4 |
1.4 | 72.1 | 66.4 | 61.9 | 75.2 | 59.2 | |
2.0 | 88.2 | 91.1 | 80.4 | 93.8 | 86.2 | |
化合物15 | 0.8 | 17.9 | 25.4 | 46.9 | 25.3 | 33.5 |
1.4 | 46.5 | 58.1 | 66.8 | 44.7 | 58.7 | |
2.0 | 91.2 | 80.8 | 96.4 | 89.8 | 89.4 | |
化合物22 | 0.8 | 29.4 | 12.8 | 34.2 | 32.7 | 21.6 |
1.4 | 55.3 | 49.1 | 58.9 | 65.2 | 58.1 | |
2.0 | 84.2 | 88.9 | 96.8 | 90.8 | 80.8 | |
化合物35 | 0.8 | 49.8 | 33.8 | 40.2 | 35.1 | 44.4 |
1.4 | 88.6 | 59.1 | 72.2 | 66.9 | 60.7 | |
2.0 | 99.7 | 96.5 | 97.8 | 90.1 | 92.6 | |
化合物40 | 0.8 | 22.8 | 18.1 | 19.2 | 33.5 | 40.4 |
1.4 | 52.6 | 49.9 | 51.3 | 66.7 | 67.1 | |
2.0 | 79.9 | 80.4 | 83.6 | 90.6 | 96.4 | |
白藜芦醇 | 20 | 27.4 | 31.2 | 38.5 | 29.4 | 21.8 |
50 | 47.2 | 41.2 | 43.8 | 39.9 | 40.1 | |
80 | 75.5 | 70.5 | 69.9 | 77.1 | 62.3 | |
5-氟尿嘧啶 | 0.8 | 48.8 | 39.6 | 46.8 | 43.9 | 36.6 |
1.4 | 77.6 | 69.8 | 72.2 | 68.6 | 69.8 | |
2.0 | 98.2 | 92.8 | 93.6 | 95.5 | 91.7 |
结果表明,化合物4、10、15、22、35、40对鼻咽癌、乳腺癌、肝癌、肺癌、大肠癌有显著的抑制作用,且抑制作用较白藜芦醇有明显提高。
实施例14:白藜芦醇及其主要衍生物对鼻咽癌及肝癌裸鼠移植癌的抑制作用
取对数生长的人鼻咽癌细胞CNE2或肝癌细胞Bel-7402,用胰酶消化后配成1×107个/ml单细胞悬液,在无菌条件下接种于BALB/C裸小鼠考右液窝皮下0.2ml/只(相当于2×106个细胞)。接种后7天,待肿瘤长至直径3-5nm时,按体积大小,随机分为对照组、5-氟尿嘧啶(阳性对照组)及化合物12、28的低、中、高剂量组、每组8只小鼠。分组后当天开始给药,腹腔注射,每天给药一次,每周6次,连用3周,停药次日称体重。处死裸鼠,剥出瘤块后称重记录,算出平均瘤重量。按下列公式计算抑瘤率,并做t测验:
抑瘤率=(1-实验组平均瘤重量/对照组平均瘤重量)×100%结果见表4
表4.白藜芦醇及其衍生物对鼻咽癌及肝癌细胞裸鼠移植瘤的抑制作用
分组 | 剂量(mg/Kg) | 瘤株与抑制率(%) | |
鼻咽癌细胞CNE2 | 肝癌细胞Bel-7402 | ||
对照组 | N.S | 0 | 0 |
5-氟尿嘧啶 | 25 | 63.5 | 58.4 |
化合物8 | 20 | 36.2 | 42.5 |
50 | 59.5 | 57.4 | |
80 | 79.8 | 72.9 | |
化合物31 | 20 | 60.1 | 55.1 |
50 | 71.8 | 68.2 | |
80 | 88.6 | 83.5 |
结果表明,化合物8、31在动物耐受剂量下,对鼻咽癌及肝癌细胞裸鼠移植瘤模型有很好的抑制作用,抑制率与剂量呈正相关。
本发明的上述实施例表明:白藜芦醇经过化学改造后,抗癌活性明显提高,且在正常剂量下,其作为药物应用是安全的。
附:化合物1~40的熔点、高分辨质谱、红外及氢谱数据
N-环丙基-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(1):
Mp 92-94℃;ESI-MS:295.1211(calc.295.1208);IR(KBr)cm-1:1682(C=N),3614(OH);1H NMR(DMSO-d6)δppm:0.46(t,2H,2×CHaHb),0.62(t,2H,2×CHaHb),3.34(m,1H,CHNH),6.65(d,1H,C4-H),6.91(d,1H,C6-H),6.74(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.14(d,1H,C7-H),8.10(d,1H,C8-H),8.62(s,1H,CH=N),9.11(s,1H,C4′-OH),9.42(s,2H,C3,5-OH)。
N-环丁基-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(2):
Mp 89-91℃;ESI-MS:309.1366(calc.309.1364);IR(KBr)cm-1:1680(C=N),3610(OH);1H NMR(DMSO-d6)δppm:1.96(t,4H,2×CH2CH),1.82(d,2H,CH2),3.24(m,1H,CHNH),6.63(d,1H,C4-H),6.91(d,1H,C6-H),6.72(d,2H,C3′,5′-H),7.33(d,2H,C2′,6′-H),7.14(d,1H,C7-H),8.12(d,1H,C8-H),8.61(s,1H,CH=N),9.11(s,1H,C4′-OH),9.41(s,2H,C3,5-OH)。
N-环戊基-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(3):
见实施例4。
N-环己基-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(4):
Mp 102-104℃;ESI-MS:337.1672(calc.337.1677);IR(KBr)cm-1:1688(C=N),3622(OH);1H NMR(DMSO-d6)δppm:1.07~1.19(m,6H,CH2CH2CH2),1.64(m,2H,CH2),1.83(m,2H,CH2),2.42(t,1H,CHNH),6.63(d,1H,C4-H),6.94(d,1H,C6-H),6.73(d,2H,C3′5′-H),7.35(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.11(d,1H,C8-H),8.59(s,1H,CH=N),9.12(s,1H,C4′-OH),9.43(s,2H,C3,5-OH)。
N-氨乙基吗啉-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(5):
Mp 161-163℃;ESI-MS:368.1738(calc.368.1736);IR(KBr)cm-1:1678(C=N),3614(OH);1H NMR(DMSO-d6)δppm:2.22(t,4H,CH2NCH2),2.35(t,2H,CH2),2.62(t,2H,CH2),3.75(t,4H,CH2OCH2),6.48(d,1H,C4-H),6.94(d,1H,C6-H),6.73(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.11(d,1H,C8-H),8.62(s,1H,CH=N),9.17(s,1H,C4′-OH),9.52(s,2H,C3,5-OH)。
N-(4-羟基-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(6):
见实施例8。
N-(4-氟-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(7):
Mp 144-146℃;ESI-MS:377.1429(calc.377.1427);IR(KBr)cm-1:1678(C=N),3616(OH);1H NMR(DMSO-d6)δppm:2.44(t,2H,ArCH2),2.72(t,2H,CH2N),6.46(d,1H,C4-H),6.64(d,2H,C3′,5′-H),6.82(d,1H,C6-H),6.88(m,4H,ArH),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),8.63(s,1H,CH=N),9.13(s,1H,C4′-OH),9.38(s,2H,C3,5-OH)。
N-(4-氯-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(8):
Mp 149-151℃;ESI-MS:393.1133(calc.393.1131);IR(KBr)cm-1:1678(C=N),3617(OH);1H NMR(DMSO-d6)δppm:2.44(t,2H,ArCH2),2.72(t,2H,CH2N),6.45(d,1H,C4-H),6.66(d,2H,C3′,5′-H),6.81(d,1H,C6-H),6.83(m,4H,ArH),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),8.42(s,1H,CH=N),9.15(s,1H,C4′-OH),9.32(s,2H,C3,5-OH)。
N-(4-溴-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(9):
Mp 162-164℃:ESI-MS:437.0628(calc.437.0626);IR(KBr)cm-1:1675(C=N),3622(OH);1H NMR(DMSO-d6)δppm:2.44(t,2H,ArCH2),2.72(t,2H,CH2N),6.46(d,1H,C4-H),6.64(d,2H,C3′,5′-H),6.79(m,4H,ArH),6.82(d,1H,C6-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),8.61(s,1H,CH=N),9.09(s,1H,C4′-OH),9.41(s,2H,C3,5-OH)。
N-(4-碘-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-亚甲基)亚胺(10):
Mp 181-183℃;ESI-MS:485.0481(calc.485.0487);IR(KBr)cm-1:1676(C=N),3628(OH);1H NMR(DMSO-d6)δppm:2.44(t,2H,ArCH2),2.72(t,2H,CH2N),6.43(d,1H,C4-H),6.61(d,2H,C3′,5′-H),6.69(m,4H,ArH),6.82(d,1H,C6-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),8.66(s,1H,CH=N),9.18(s,1H,C4′-OH),9.33(s,2H,C3,5-OH)。
N-环丙基-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(11):
Mp 72-74℃;ESI-MS:337.1682(calc.337.1677);IR(KBr)cm-1:1688(C=N);1H NMR(DMSO-d6)δppm:0.46(t,2H,2×CHaHb),0.62(t,2H,2×CHaHb),3.34(m,1H,CHNH),3.77(s,3H,C4′-OCH3),3.84(s,3H,C3-OCH3),3.86(s,3H,C5-OCH3),6.65(d,1H,C4-H),6.91(d,1H,C6-H),6.74(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.14(d,1H,C7-H),8.10(d,1H,C8-H),8.62(s,1H,CH=N)。
N-环丁基-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(12):
Mp 67-69℃;ESI-MS:351.1838(calc.351.1834);IR(KBr)cm-1:1680(C=N);1H NMR(DMSO-d6)δppm:1.96(t,4H,2×CH2CH),1.82(d,2H,CH2),3.24(m,1H,CHNH),3.81(s,3H,C4′-OCH3),3.87(s,3H,C3-OCH3),3.89(s,3H,C5-OCH3),6.61(d,1H,C4-H),6.94(d,1H,C6-H),6.73(d,2H,C3′,5′-H),7.33(d,2H,C2′6′-H),7.14(d,1H,C7-H),8.12(d,1H,C8-H),8.63(s,1H,CH=N)。
N-环戊基-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(13):
见实施例3。
N-环己基-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(14):
Mp 81-83℃;ESI-MS:379.2149(calc.379.2147);IR(KBr)cm-1:1681(C=N);1H NMR(DMSO-d6)δppm:1.07~1.19(m,6H,CH2CH2CH2),1.64(m,2H,CH2),1.83(m,2H,CH2),2.42(t,1H,CHNH),3.71(s,3H,C4′-OCH3),3.82(s,3H,C3-OCH3),3.88(s,3H,C5-OCH3),6.69(d,1H,C4-H),6.92(d,1H,C6-H),6.73(d,2H,C3′,5′-H),7.38(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.11(d,1H,C8-H),8.69(s,1H,CH=N)。
N-氨乙基吗啉-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(15):
Mp 142-144℃;ESI-MS:410.2201(calc.410.2205);IR(KBr)cm-1:1678(C=N);1H NMR(DMSO-d6)δppm:2.22(t,4H,CH2NCH2),2.35(t,2H,CH2),2.62(t,2H,CH2),3.71(t,4H,CH2OCH2),3.76(s,3H,C4′-OCH3),3.85(s,3H,C3-OCH3),3.86(s,3H,C5-OCH3),6.48(d,1H,C4-H),6.94(d,1H,C6-H),6.75(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.18(d,1H,C7-H),8.12(d,1H,C8-H),8.59(s,1H,CH=N)。
N-(4-羟基-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(16):
见实施例7。
N-(4-氟-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(17):
Mp 133-135℃;ESI-MS:419.1899(calc.419.1896);IR(KBr)cm-1:1678(C=N);
1H NMR(DMSO-d6)δppm:2.44(t,2H,ArCH2),2.71(t,2H,CH2N),3.81(s,3H,C4′-OCH3),3.87(s,3H,C3-OCH3),3.90(s,3H,C5-OCH3),6.46(d,1H,C4-H),6.64(d,2H,C3′,5′-H),6.82(d,1H,C6-H),6.87(m,4H,ArH),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.33(d,1H,C8-H),8.67(s,1H,CH=N)。
N-(4-氯-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(18):
Mp 149-151℃;ESI-MS:435.1605(calc.435.1601);IR(KBr)cm-1:1678(C=N),3617(OH);1H NMR(DMSO-d6)δppm:2.44(t,2H,ArCH2),2.72(t,2H,CH2N),3.82(s,3H,C4′-OCH3),3.89(s,3H,C3-OCH3),3.92(s,3H,C5-OCH3),6.46(d,1H,C4-H),6.64(d,2H,C3′,5′-H),6.82(d,1H,C6-H),6.83(m,4H,ArH),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),8.59(s,1H,CH=N)。
N-(4-溴-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(19):
Mp 169-171℃;ESI-MS:479.1099(calc.479.1096);IR(KBr)cm-1:1676(C=N),3622(OH);1H NMR(DMSO-d6)δppm:2.45(t,2H,ArCH2),2.71(t,2H,CH2N),3.82(s,3H,C4′-OCH3),3.83(s,3H,C3-OCH3),3.91(s,3H,C5-OCH3),6.49(d,1H,C4-H),6.63(d,2H,C3′,5-H),6.82(d,1H,C6-H),6.84(m,4H,ArH),7.54(d,2H,C2′,6′-H),7.12(d,1H,C7-H),7.39(d,1H,C8-H),8.64(s,1H,CH=N)。
N-(4-碘-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-亚甲基)亚胺(20):
Mp 169-171℃;ESI-MS:527.0952(calc.527.0957);IR(KBr)cm-1:1676(C=N),3622(OH);1H NMR(DMSO-d6)δppm:2.45(t,2H,ArCH2),2.71(t,2H,CH2N),3.81(s,3H,C4′-OCH3),3.87(s,3H,C3-OCH3),3.90(s,3H,C5-OCH3),6.49(d,1H,C4-H),6.63(d,2H,C3′,5′-H),6.82(d,1H,C6-H),6.84(m,4H,ArH),7.54(d,2H,C2′,6′-H),7.12(d,1H,C7-H),7.39(d,1H,C8-H),8.61(s,1H,CH=N)。
N-环丙基-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(21):
Mp 82-84℃;ESI-MS:297.1362(calc.297.1364);IR(KBr)cm-1:1175(C-N),3310(NH),3620(OH);1H NMR(DMSO-d6)δppm:0.46(t,2H,2×CHaHb),0.62(t,2H,2×CHaHb),3.32(m,1H,CHNH),3.81(s,2H,CH2),6.65(d,1H,C4-H),6.91(d,1H,C6-H),6.74(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.14(d,1H,C7-H),8.10(d,1H,C8-H),8.61(s,1H,CH=N),9.13(s,1H,C4′-OH),9.46(s,2H,C3,5-OH)。
N-环丁基-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(22):
Mp 82-84℃;ESI-MS:311.1522(calc.311.1521);IR(KBr)cm-1:1172(C-N),3314(NH),3618(OH);1H NMR(DMSO-d6)δppm:1.95(t,4H,2×CH2CH),1.84(d,2H,CH2),3.26(m,1H,CHNH),3.84(s,2H,CH2),6.63(d,1H,C4-H),6.91(d,1H,C6-H),6.72(d,2H,C3′,5′-H),7.33(d,2H,C2′,6′-H),7.14(d,1H,C7-H),8.12(d,1H,C8-H),8.61(s,1H,CH=N),9.11(s,1H,C4′-OH),9.41(s,2H,C3,5-OH)。
N-环戊基-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(23):
见实施例6。
N-环己基-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(24):
Mp 87-89℃;ESI-MS:339.1838(calc.339.1834);IR(KBr)cm-1:1172(C-N),3314(NH),3618(OH);1H NMR(DMSO-d6)δppm:1.07~1.21(m,6H,CH2CH2CH2),1.66(m,2H,CH2),1.81(m,2H,CH2),2.42(t,1H,CHNH),3.81(s,2H,ArCH2),6.63(d,1H,C4-H),6.94(d,1H,C6-H),6.73(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.11(d,1H,C8-H),9.09(s,1H,C4′-OH),9.38(s,2H,C3,5-OH)。
N-氨乙基吗啉-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(25):
Mp 148-150℃;ESI-MS:370.1898(calc.370.1892);IR(KBr)cm-1:1160(C-N),3322(NH),3632(OH);1H NMR(DMSO-d6)δppm:2.22(t,4H,CH2NCH2),2.35(t,2H,CH2),2.62(t,2H,CH2),3.75(t,4H,CH2OCH2),3.81(s,2H,ArCH2),6.46(d,1H,C4-H),6.94(d,1H,C6-H),6.74(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.11(d,1H,C8-H),9.19(s,1H,C4′-OH),9.43(s,2H,C3,5-OH)。
N-(4-羟基-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(26):
见实施例10。
N-(4-氟-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(27):
Mp 124-126℃;ESI-MS:379.1580(calc.379.1583);IR(KBr)cm-1:1172(C-N),3314(NH),3618(OH);1H NMR(DMSO-d6)δppm:2.45(t,2H,ArCH2),2.74(t,2H,CH2N),3.82(s,2H,ArCH2N),6.46(d,1H,C4-H),6.82(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),6.89(m,4H,ArH),9.14(s,1H,C4′-OH),9.44(s,2H,C3,5-OH)。
N-(4-氯-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(28):
Mp 129-131℃;ESI-MS:395.1293(calc.395.1288);IR(KBr)cm-1:1172(C-N),3315(NH),3616(OH);1H NMR(DMSO-d6)δppm:2.45(t,2H,ArCH2),2.74(t,2H,CH2N),3.82(s,2H,ArCH2N),6.46(d,1H,C4-H),6.82(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),6.78(m,4H,ArH),9.11(s,1H,C4′-OH),9.46(s,2H,C3,5-OH)。
N-(4-溴-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(29):
Mp 136-138℃;ESI-MS:439.0779(calc.439.0783);IR(KBr)cm-1:1178(C-N),3319(NH),3617(OH);1H NMR(DMSO-d6)δppm:2.45(t,2H,ArCH2),2.74(t,2H,CH2N),3.82(s,2H,ArCH2N),6.46(d,1H,C4-H),6.82(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),6.76(m,4H,ArH),9.18(s,1H,C4′-OH),9.53(s,2H,C3,5-OH)。
N-(4-碘-苯乙基)-(3,4,5′-三羟基二苯乙烯基-2-甲基)胺(30):
Mp 149-151℃;ESI-MS:487.0648(calc.487.0644);IR(KBr)cm-1:1178(C-N),3319(NH),3622(OH);1H NMR(DMSO-d6)δppm:2.45(t,2H,ArCH2),2.74(t,2H,CH2N),3.82(s,2H,ArCH2N),6.46(d,1H,C4-H),6.81(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.36(d,1H,C8-H),6.68(m,4H,ArH),9.13(s,1H,C4′-OH),9.42(s,2H,C3,5-OH)。
N-环丙基-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(31):
Mp 48-50℃;ESI-MS:367.2145(calc.367.2147);IR(KBr)cm-1:1175(C-N),3310(NH);1H NMR(DMSO-d6)δppm:0.46(t,2H,2×CHaHb),0.62(t,2H,2×CHaHb),3.32(m,1H,CHNH),3.81(s,2H,CH2),3.78(s,3H,C4′-OCH3),3.90(s,3H,C3-OCH3),3.92(s,3H,C5-OCH3),6.65(d,1H,C4-H),6.91(d,1H,C6-H),6.74(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.14(d,1H,C7-H),8.09(d,1H,C8-H)。
N-环丁基-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(32):
Mp41-43℃;ESI-MS:381.2307(calc.381.2303);IR(KBr)cm-1:1172(C-N),3314(NH):1H NMR(DMSO-d6)δppm:1.95(t,4H,2×CH2CH),1.84(d,2H,CH2),3.26(m,1H,CHNH),3.84(s,2H,CH2),3.78(s,3H,C4′-OCH3),3.90(s,3H,C3-OCH3),3.92(s,3H,C5-OCH3),6.65(d,1H,C4-H),6.91(d,1H,C6-H),6.72(d,2H,C3′,5′-H),7.33(d,2H,C2′,6′-H),7.14(d,1H,C7-H),8.09(d,1H,C8-H)。
N-环戊基-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(33):
见实施例5。
N-环己基-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(34):
Mp 59-61℃;ESI-MS:409.2610(calc.409.2616);IR(KBr)cm-1:1172(C-N),3314(NH);1H NMR(DMSO-d6)δppm:1.07~1.21(m,6H,CH2CH2CH2),1.66(m,2H,CH2),1.81(m,2H,CH2),2.42(t,1H,CHNH),3.81(s,2H,ArCH2),3.79(s,3H,C4′-OCH3),3.90(s,3H,C3-OCH3),3.91(s,3H,C5-OCH3),6.63(d,1H,C4-H),6.94(d,1H,C6-H),6.73(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.12(d,1H,C8-H)。
N-氨乙基吗啉-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(35):
Mp 64-66℃;ESI-MS:412.2365(calc.412.2362);IR(KBr)cm-1:1160(C-N),3322(NH);1H NMR(DMSO-d6)δppm:2.22(t,4H,CH2NCH2),2.35(t,2H,CH2),2.62(t,2H,CH2),3.75(t,4H,CH2OCH2),3.81(s,2H,ArCH2),3.79(s,3H,C4′-OCH3),3.90(s,3H,C3-OCH3),3.92(s,3H,C5-OCH3),6.48(d,1H,C4-H),6.94(d,1H,C6-H),6.73(d,2H,C3′,5′-H),7.35(d,2H,C2′,6′-H),7.12(d,1H,C7-H),8.11(d,1H,C8-H)。
N-(4-羟基-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(36):
见实施例9。
N-(4-氟-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(37):
Mp 91-93℃;ESI-MS:421.2057(calc.421.2053);IR(KBr)cm-1:1172(C-N),3314(NH);1H NMR(DMSO-d6)δppm:2.51(t,2H,ArCH2),2.74(t,2H,CH2N),3.82(s,2H,ArCH2N),3.77(s,3H,C4′-OCH3),3.89(s,3H,C3-OCH3),3.90(s,3H,C5-OCH3),6.45(d,1H,C4-H),6.82(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.11(d,1H,C7-H),7.35(d,1H,C8-H),6.88(m,4H,ArH)。
N-(4-氯-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(38):
Mp 98-100℃;ESI-MS:437.1761(calc.437.1757);IR(KBr)cm-1:1172(C-N),3315(NH);1H NMR(DMSO-d6)δppm:2.41(t,2H,ArCH2),2.73(t,2H,CH2N),3.81(s,2H,ArCH2N),3.76(s,3H,C4′-OCH3),3.90(s,3H,C3-OCH3),3.91(s,3H,C5-OCH3),6.46(d,1H,C4-H),6.82(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.12(d,1H,C7-H),7.35(d,1H,C8-H),6.79(m,4H,ArH)。
N-(4-溴-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(39):
Mp 107-109℃;ESI-MS:481.1255(calc.481.1252);IR(KBr)cm-1:1178(C-N),3319(NH);1H NMR(DMSO-d6)δppm:2.46(t,2H,ArCH2),2.73(t,2H,CH2N),3.82(s,2H,ArCH2N),3.77(s,3H,C4′-OCH3),3.89(s,3H,C3-OCH3),3.90(s,3H,C5-OCH3),6.46(d,1H,C4-H),6.82(d,1H,C6-H),6.64(d,2H,C3′,5′-H),7.54(d,2H,C2′,6′-H),7.09(d,1H,C7-H),7.34(d,1H,C8-H),6.75(m,4H,ArH)。
N-(4-碘-苯乙基)-(3,4,5′-三甲氧基二苯乙烯基-2-甲基)胺(40):
Mp 112-114℃;ESI-MS:529.1116(calc.529.1113);IR(KBr)cm-1:1178(C-N),3322(NH);1H NMR(DMSO-d6)δppm:2.45(t,2H,ArCH2),2.74(t,2H,CH2N),3.83(s,2H,ArCH2N),3.79(s,3H,C4′-OCH3),3.91(s,3H,C3-OCH3),3.92(s,3H,C5-OCH3),6.44(d,1H,C4-H),6.85(d,1H,C6-H),6.61(d,2H,C3′,5′-H),7.55(d,2H,C2′,6′-H),7.12(d,1H,C7-H),7.33(d,1H,C8-H),6.68(m,4H,ArH)。
Claims (7)
4.一种制备权利要求1所述的白藜芦醇的衍生物的方法,其特征是:将权利要求3所得到的产物式II化合物与BBr3在二氯甲烷中反应,式II化合物与BBr3的物质的量之比为1∶1~1∶1.5,即得到结构式如式II的白藜芦醇衍生物,但式中R1=H,R3仍为环丙基、环丁基、环戊基或环己基,或者R3为具有如下化学式A或B结构的基团:
式B中的X为氟、氯、溴、碘或羟基。
5.一种制备权利要求1所述的白藜芦醇的衍生物的方法,其特征是:将权利要求3所得到的产物式H化合物溶于无水乙醇中,分批加入NaBH4,式II化合物与NaBH4的物质的量之比为1∶0.5~1∶1.5,常温下搅拌2小时,即得到结构式如式III的白藜芦醇的衍生物,
式III中R1=CH3,R3=环丙基、环丁基、环戊基或环己基,或者R3为具有如下化学式A或B结构的基团:
式B中的X为氟、氯、溴、碘或羟基。
6.一种制备权利要求1所述的白藜芦醇的衍生物的方法,其特征是:将权利要求5所得到的产物式III化合物与BBr3在二氯甲烷中反应,式III化合物与BBr3的物质的量之比为1∶1~1∶1.5,即得到结构式如式III的白藜芦醇的衍生物,但式中R1=H,R3仍为环丙基、环丁基、环戊基或环己基,或者R3为具有如下化学式A或B结构的基团:
式B中的X为氟、氯、溴、碘或羟基。
7.权利要求1所述的白藜芦醇的衍生物在制备抗肿瘤药物中的应用。
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