CN111848633B - 一类香豆素-Tröger’s base类Fe3+荧光探针及其制备方法 - Google Patents
一类香豆素-Tröger’s base类Fe3+荧光探针及其制备方法 Download PDFInfo
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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Abstract
Description
技术领域
背景技术
铁作为人体必须的微量元素,是血红蛋白、肌红蛋白的必要成分,并参与氧气和二氧化碳的转运和交换。但过量的铁会对人体造成伤害。因此,建立快速高效的检测方法具有重要意义。目前检测铁离子的方法主要有原子吸收光谱法、高效液相色谱法等。但部分方法处理繁琐、成本高、需要大型仪器和专业人员操作。荧光光谱法具有响应速度快、成本低、灵敏度高等优点而被广泛应用于铁离子的识别,其中荧光探针的合理设计是高效识别Fe3+的关键。已经设计合成出大量荧光探针用来识别自然环境中的Fe3+,但细胞内内源性Fe3+的检测、成像、示踪的相关报道还不多,且尚无以base(TB)为骨架的Fe3+荧光探针。
香豆素(coumarin)是一种常见的荧光团,具有理想的光物理特性,如可见发射波长、高荧光量子产率和大斯托克斯位移等。
发明内容
本发明公开了一种以对溴苯胺、多聚甲醛等多种化合物为原料通过多步反应制得的具有抗肿瘤活性、红色固态发光、可用于Fe3+识别的香豆素-base衍生物。同时测试了该类化合物的固态发光性质、抗肿瘤活性和对人肺癌细胞(A549)的成像能力,最终筛选到了一批具有高活性的产物,为红色固态发光材料、抗肿瘤药及肿瘤细胞造影剂的进一步发展提供了基础。
本发明的技术方案具体如下:
方法(1)
将下式中间体5、中间体3和三滴哌啶溶于无水乙醇中,回流一段,反应结束后冷却至室温,旋干溶剂,粗产物经柱层析纯化得化合物目标产物;
方法(2)
将将下式所示中间体5、中间体4和三滴哌啶溶解在乙醇中加热回流48h,反应结束后冷却至室温,旋干溶剂,粗产物经柱层析纯化得目标产物;
方法(3)
将3-甲氧基-4-溴苯胺8和多聚甲醛加入圆底烧瓶内,置于低温槽中搅拌条件下向烧瓶内缓慢滴加三氟乙酸,之后室温下反应若干天;TLC追踪至反应完全后,将反应物倒入冰水中淬灭,然后用氨水调节pH至9-10,冷却至室温,用二氯甲烷萃取,旋干得粗产物;粗产物中倒入丙酮加热,全部溶解后,置于室温下重结晶,抽滤并用丙酮洗涤,得下式中间体9
将中间体9加入到干净的圆底烧瓶内,抽换气,置于低温槽中搅拌条件下向烧瓶内加入无水四氢呋喃,滴加正丁基锂,反应一段时间后滴加无水DMF,之后置于室温下反应;TLC追踪至反应完全后,用二氯甲烷萃取,旋干得粗产物;粗产物经柱层析提纯得下式所示中间体10
将下式所示中间体5、中间体10和三滴哌啶溶解在乙醇中加热回流,反应结束后冷却至室温,减压除去溶剂得到粗产物,通过柱层析纯化得目标产物
方法(4)
将下式所示中间体12、中间体3和三滴哌啶溶解在乙醇中加热回流,反应结束后冷却至室温,减压除去溶剂得到粗产物,通过柱层析纯化得目标产物
与现有技术相比,本发明的有益技术效果:
(2)产物发光性能优异,Stokes位移大,溶液发射绿色发光,固态下发射红色荧光,在制备新型高亮度红色固态发光材料方面具有应用潜力;
(3)所有产物对Fe3+均具有高度特异性识别能力,在制备Fe3+荧光探针方面具有应用潜力;
(4)一个产物对人三阴性乳腺癌细胞(231)具有较好的抑制效果,在抗肿瘤新药研发方面具有应用潜力;
(5)部分产物可对人非小肺癌细胞(A549)进行成像,在肿瘤细胞红树湾造影剂研发方面具有应用潜力。
附图说明
图1不同金属离子、阴离子和氨基酸存在下6的荧光强度变化率;
图2不同浓度Fe3+存在下化合物6的荧光发射光谱(左)和标准曲线(右);
图3化合物6随Fe3+浓度变化的紫外吸收光谱;
图4 6-Fe3+体系的Job’s曲线;
图5化合物10在A549的荧光成像。
具体实施方式
实施例
(1)化合物6的合成,包括:
中间体1-5参照文献方法合成。将中间体5(2.0mmol)、中间体3(2.2mmol)和三滴哌啶溶于无水乙醇(15.0mL)中,回流48h,反应结束后冷却至室温,旋干溶剂,粗产物经柱层析纯化(V石油醚:V乙酸乙酯=3:1)得化合物6(0.79g,69%)。
(2)化合物7的合成:
将中间体5(2.0mmol)、中间体4(2.2mmol)和三滴哌啶溶解在乙醇(15.0mL)中加热回流48h,反应结束后冷却至室温,旋干溶剂,粗产物经柱层析纯化(V石油醚:V乙酸乙酯=3:1)得化合物7(0.69g,66%)。
(3)化合物11的合成:
中间体10的合成:
将3-甲氧基-4-溴苯胺8(50.0mmol)和多聚甲醛(100.0mmol)加入200.0mL圆底烧瓶内,置于低温槽中调温至-15℃,搅拌下向烧瓶内缓慢滴加三氟乙酸(100.0mL),之后室温下反应7天。TLC追踪至反应完全后,将反应物倒入冰水中淬灭,然后用氨水调节pH至9-10,冷却至室温,用二氯甲烷萃取,旋干得粗产物。粗产物中倒入丙酮加热至70℃,全部溶解后,置于室温下重结晶,抽滤并用丙酮洗涤,得中间体9(12.48g,57%)。
中间体10的合成:
将中间体9(5.0mmol)加入到干净的100.0mL圆底烧瓶内,抽换气三次后,置于低温槽中调温至-78℃,搅拌下向烧瓶内加入20.0mL无水四氢呋喃,滴加2.5mL正丁基锂,反应1h后滴加0.6mL无水DMF,之后置于室温下反应12h。TLC追踪至反应完全后,用二氯甲烷萃取,旋干得粗产物。粗产物经柱层析提纯(V石油醚:V乙酸乙酯=5:1)得中间体10(0.35g,18%)。
化合物11的合成:
将中间体5(2.0mmol)、中间体10(2.2mmol)和三滴哌啶溶解在乙醇(15.0mL)中加热回流48h,反应结束后冷却至室温,减压除去溶剂得到粗产物,通过柱层析纯化(V石油醚:V乙酸乙酯=3:1)得化合物11(0.65g,52%)。
(4)化合物13的合成:
中间体12参照文献方法合成。将中间体12(2.0mmol)、中间体3(2.2mmol)和三滴哌啶溶解在乙醇(15.0mL)中加热回流48h,反应结束后冷却至室温,减压除去溶剂得到粗产物,通过柱层析纯化(V石油醚:V乙酸乙酯=3:1)得化合物13(0.69g,64%)。
分别称取1×10-5mol的6a-6i于100mL容量瓶中,DMF定容,配制成浓度为1×10- 4mol·L-1的工作溶液。再移取1mL工作液于10mL容量瓶中,用DMF稀释至刻度,得到浓度为1×10-5mol·L-1溶液,测得溶液荧光光谱数据如表1所示。
将样品平铺并压片,使用FL-4600荧光分光光度计测试得到了产物的固态荧光光谱数据,如表1所示。
表1产物的光谱数据
a溶液中紫外吸收波长;b摩尔消光系数ε=A/bc,单位为1×105L·mol-1·cm-1;c溶液中荧光发射波长;d溶液中Stokes位移;e荧光量子产率;f荧光亮度,单位为1×104L·mol-1·cm-1;g固态激发波长;h固态荧光发射波长;i固态Stokes位移。
产物在溶液中发光性质的特点:
(1)相比于香豆素中间体5,引入TB后化合物的荧光发射波长红移了28-43nm,Stokes位移在108-123nm之间,与香豆素中间体5相比略有增大,说明TB骨架对分子的发光性质有影响。
(2)化合物的荧光亮度为1.3-5.5×104L·mol-1·cm-1,与已报道的荧光亮度最高值(3.2×104L·mol-1·cm-1)相当。
产物在固态下的发光性质具有以下特点:
(1)化合物的固态荧光发射波长在533-616nm之间,相比于中间体5发生了较大的红移。
(2)与溶液相比,产物的固态荧光发射波长均发生了红移,Stokes位移在63-149nm之间,说明化合物在固态下荧光性质发生了变化。
取代基的影响:
比较香豆素中间体5和化合物6,可看出含有TB骨架的6的Stokes位移明显增大;含有不同取代基的TB衍生物6、7和11的发光性质相差不大;6、7、11和13的固态荧光最大发射波长进入了红外区,且具有更大的Stokes位移,说明TB骨架对产物固态发光性质影响较大。
(1)对金属离子的识别
分别称取1×10-5mol化合物5、6、7、11和13溶于少量DMSO后用DMSO定容,配制成化合物浓度为1×10-4mol·L-1的工作溶液。金属离子(Cu2+、Cr2+、Al3+、Fe3+、Fe2+、Zn2+、Zr4+、Ca2 +、Cd2+、Co2+、Ni2+)配制成浓度为1×10-2mol·L-1的的水溶液(二次水)。分别依次量取1mL化合物工作溶液、1mL金属离子溶液、1mL HEPES缓冲溶液于10mL比色管中,DMSO定容,在相应化合物最大激发波长激发下测得了体系的荧光发射光谱(λex=399-429nm),见表2-4。由表2-4可知:
(1)连有TB骨架的化合物6、7、11和13均对Fe3+具有最大的荧光淬灭效率,η分别为-73%,-80%,-60%和-83%。
(2)各化合物对Fe3+的作用最大的是13,可能是由于13中香豆素片段上的取代基是N,N-二甲基氨基,而其他产物中香豆素片段上的取代基是N,N-二乙基氨基。前者的空间位阻小于后者,与Fe3+的作用更为顺利。该结果说明,产物分子的空间位阻是影响其与Fe3+作用的主要因素。
表2化合物5和6对金属离子的作用
a加入金属离子后化合物的荧光强度变化率,η=(I-I0)/I0×100%。
表3化合物7对金属离子的作用
a加入金属离子后化合物的荧光强度变化率,η=(I-I0)/I0×100%。
表4化合物11和13对金属离子的作用
a加入金属离子后化合物的荧光强度变化率,η=(I-I0)/I0×100%。
(2)化合物6对Fe3+的识别
选取了十一种金属离子、五种阴离子和三种生物硫醇作为识别对象,测试了化合物6对其识别能力,制作了柱状图(图1)。由图1可知,6对Fe3+具有较好的选择性识别作用(λex=427nm,浓度为1×10-5mol·L-1)。
分别依次量取1mL 6的工作溶液(1×10-4mol·L-1)、1mL HEPES缓冲溶液和7mLDMSO于10mL比色管中,再从浓度为1×10-3mol·L-1的Fe3+溶液中分别取不同体积(0.01-1.0mL)的溶液至10mL容量瓶中,二次蒸馏水定容,配制浓度从1×10-6-1×10-4mol·L-1的Fe3+溶液,来观察其对6荧光的影响(λex=427nm)。
由图2可知,化合物6的荧光强度随着Fe3+浓度的增加而减小,直至完全淬灭。绘制了化合物6对Fe3+的标准曲线(图2右,R=0.96,LOD=4.1×10-5mol·L-1)。
为探讨Fe3+与化合物6的作用,测试了加入不同浓度Fe3+后6的紫外吸收光谱(图3中,化合物6的浓度为2×10-7mol·L-1)。由图3可以看出,随着Fe3+浓度的增大,化合物的λabs从427nm移动到471nm处,说明有新的物质生成。
为探明该新物质的组成,在6和Fe3+总浓度(1×10-5mol·L-1)不变的条件下,在1:9到9:1的范围内,改变6和Fe3+的摩尔比,测试了各溶液的荧光强度,绘制了Job’s曲线(图4)。由图4可知,当铁离子浓度与铁离子和6总浓度比值为0.6的时候出现拐点,说明化合物6能够与Fe3+以2:3的方式形成配位键(λex=427nm)。
通过MTT法测试了产物对人三阴性乳腺癌细胞(MDA-MB-231)的抗肿瘤活性。称取0.5g MTT溶于100mL磷酸缓冲溶液(PBS)中,配成浓度为5μg/mL的MTT溶液,用0.22μm滤膜过滤以除去溶液里的细菌,放4℃中避光保存即可。在配制和保存的过程中,容器用铝箔纸包裹,使用前要先避光融化。融化后再吸取10μL MTT溶液加入到平底96孔板各孔中,然后在培养箱中培养4h,弃掉上层清液后向各孔中加入100μL DMSO溶液,震荡混匀,测量OD值,计算IC50值。一般IC50值越小,说明化合物对肿瘤细胞抑制效果越好。
lgIC50=Xm-I(P-(3-Pm-Pn)/4)
Xm:lg最大剂量;I:g(最大剂量/相临计量);P:阳性反应率;Pm:最大阳性反应率;Pn:最小阳性反应率
如表5所示,化合物7对人三阴性乳腺癌细胞(231)具有较好抑制作用。化合物7的TB骨架上连有醛基,而其他几种化合物TB骨架上连的是Br,具体原因有待进一步研究。其他几种化合物可能是由于在测试溶解性较差,未表现出对231细胞的抑制活性。
表5化合物7对231细胞的IC50(μg/mL)a
aIC50大于50标记为-
表6化合物在斑马鱼细胞中的存活率和孵化率
aControl为不加化合物的空白对照组
通过记录加入化合物后斑马鱼胚胎的孵化率和存活率测试了化合物对斑马鱼的毒性[95-96](表6)。由表6可知,加入不同浓度的化合物6、7、11、13后斑马鱼的存活率均为100%。化合物6的浓度为50μg·mL-1时斑马鱼胚胎的孵化率为96%,高于空白样,7的浓度为50μg·mL-1时孵化率为90%,说明化合物6和化合物7对斑马鱼的毒性很低。
以化合物6为例初步研究了其对人非小肺癌细胞(A549)的成像。如图5所示,左边为明场成像,中间是绿色激发光的成像,右边是蓝色激发光的成像。与明场相比可以看出,化合物可进入细胞内并对细胞进行染色。
化合物6的结构式为:
分子式为:C31H28BrN3O3
中文命名为:
(E)-3-(3-(8-溴-(6H,12H-5,11-桥亚甲二苯并[b,f][1,5]二氮芳辛-2-基)丙烯酰基)-7-(二乙基氨基)-2H-色烯-2-酮
英文命名为:
(E)-3-(3-(8-bromo-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2-yl)acryloyl)-7-(diethylamino)-2H-chromen-2-one
外观:灰红色固体
熔点:224.3-224.9℃
核磁共振氢谱:1H NMR(400MHz,CDCl3)δ8.52(s,1H,pyran-H),8.02(d,J=16.0Hz,1H,C=C-H),7.69(d,J=15.6Hz,1H,Ar-H),7.49(d,J=8Hz,1H,C=C-H),7.41(d,J=8.8Hz,1H,Ar-H),7.30-7.27(m,2H,Ar-H),7.15(d,J=8.4Hz,1H,Ar-H),7.07-7.05(m,2H,Ar-H),6.61(dd,J1=9.2Hz,J2=2.4Hz,1H,Ar-H),6.48(d,J=2.4Hz,1H,Ar-H),4.70(t,J=16.4Hz,2H,-CH2-bridge),4.36-4.28(m,4H,TB-CH2*2),3.45(q,J=7.2Hz,4H,-CH2CH3*2),1.24(t,J=7.2Hz,6H,-CH2CH3*2).
核磁共振碳谱:13C NMR(100MHz,CDCl3)δ185.8,160.9,158.8,153.0,147.9,142.2,131.9,131.5,130.7,129.3,128.3,128.0,127.6,127.4,126.9,125.7,124.1,123.9,123.3,116.2,109.9,108.2,96.6,76.4,66.4,58.6,58.5,44.2,12.5.
质谱:HRMS(ESI)m/z:calcd for C31H28BrN3O3[M+Na]+:569.1314;found:592.1198.
中间体1-5参照文献方法合成。将中间体5(2.0mmol)、中间体3(2.2mmol)和三滴哌啶溶于无水乙醇(15.0mL)中,回流48h,反应结束后冷却至室温,旋干溶剂,粗产物经柱层析纯化(V石油醚:V乙酸乙酯=3:1)得化合物6(0.79g,69%)。
化合物7的结构式为:
分子式为:C32H29N3O4
中文命名为:
(E)-8-(3-(7-(二乙基氨基)-2-氧代-2H-色烯-3-基)-3-氧代丙-1-烯-1-基)-6H,12H-5,11-桥亚甲二苯并[b,f][1,5]二氮芳辛-2-醛
英文命名为:
(E)-8-(3-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-3-oxoprop-1-en-1-yl)-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2-carbaldehyde
外观:灰红色固体
熔点:235.2-235.7℃
核磁共振氢谱:1H NMR(400MHz,CDCl3)δ9.85(s,1H,-CHO),8.53(s,1H,pyran-H),8.03(d,J=15.6Hz,1H,C=C-H),7.73-7.67(m,2H,Ar-H),7.51(d,J=9.6Hz,2H,C=C-H),7.41(d,J=8.8Hz,1H,Ar-H),7.33(d,J=8.0Hz,1H,Ar-H),7.28(s,1H,Ar-H),7.24(d,J=8.0Hz,1H,Ar-H),6.62(dd,J1=9.2Hz,J2=2.4Hz,1H,Ar-H),6.48(d,J=2.4Hz,1H,Ar-H),4.81(dd,J1=16.8Hz,J2=8.8Hz,2H,-CH2-bridge),4.45-4.28(m,4H,TB-CH2*2),3.47(q,J=7.2Hz,4H,-CH2CH3*2),1.25(t,J=7.2Hz,6H,-CH2CH3*2).
核磁共振碳谱:13C NMR(100MHz,CDCl3)δ190.7,190.6,185.9,160.5,158.3,153.8,152.6,148.4,142.1,132.0,131.4,128.9,128.6,128.0,127.9,127.3,126.9,125.2,124.9,123.8,116.2,109.5,108.2,96.2,76.8,66.2,58.3,58.1,44.7,12.0.
质谱:HRMS(ESI)m/z:calcd for C32H29N3O4[M+Na]+:519.2158;found:542.2028.
将中间体5(2.0mmol)、中间体4(2.2mmol)和三滴哌啶溶解在乙醇(15.0mL)中加热回流48h,反应结束后冷却至室温,旋干溶剂,粗产物经柱层析纯化(V石油醚:V乙酸乙酯=3:1)得化合物7(0.69g,66%)。
化合物11的结构式为:
分子式为:C33H32N3O5
中文命名为:
(E)-3-(3-(8-溴-3,9-二甲氧基-(6H,12H-5,11-桥亚甲二苯并[b,f][1,5]二氮芳辛-2-基)丙烯酰基)-7-(二乙基氨基)-2H-色烯-2-酮
英文命名为:
(E)-3-(3-(8-bromo-3,9-dimethoxy-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2-yl)acryloyl)-7-(diethylamino)-2H-chromen-2-one
外观:灰红色固体
熔点:244.8-245.5℃
核磁共振氢谱:1H NMR(400MHz,CDCl3)δ8.48(s,1H,pyran-H),7.92(s,2H,Ar-H),7.52(s,1H,C=C-H),7.36(s,1H,Ar-H),7.28(s,1H,Ar-H),6.82-6.71(m,3H,Ar-H),6.49(s,1H,C=C-H),4.71-4.59(m,2H,-CH2-bridge),4.35-4.19(m,4H,TB-CH2*2),3.88(s,6H,-OCH3*2),3.49(s,4H,-CH2CH3*2),1.24(s,6H,-CH2CH3*2).
核磁共振碳谱:13C NMR(100MHz,CDCl3)δ185.6,161.4,159.7,157.5,157.1,155.4,147.8,147.3,143.4,142.0,131.1,130.7,128.1,124.8,123.8,123.3,122.5,122.4,110.8,110.8,108.1,107.5,97.3,76.7,66.4,58.5,58.1,57.8,44.2,12.4.
质谱:HRMS(ESI)m/z:calcd for C33H32N3O5[M+Na]+:629.1525;found:654.1410.
将中间体5(2.0mmol)、中间体10(2.2mmol)和三滴哌啶溶解在乙醇(15.0mL)中加热回流48h,反应结束后冷却至室温,减压除去溶剂得到粗产物,通过柱层析纯化(V石油醚:V乙酸乙酯=3:1)得化合物11(0.65g,52%)。
化合物13的结构式为:
分子式为:C29H24BrN3O3
中文命名为:
(E)-3-(3-(8-溴-(6H,12H-5,11-桥亚甲二苯并[b,f][1,5]二氮芳辛-2-基)丙烯酰基)-7-(二甲基氨基)-2H-色烯-2-酮
英文命名为:
(E)-3-(3-(8-bromo-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2-yl)acryloyl)-7-(dimethylamino)-2H-chromen-2-one
外观:黄色固体
熔点:237.7-238.4℃
核磁共振氢谱:1H NMR(400MHz,CDCl3)δ8.55(s,1H,pyran-H),8.03(d,J=15.6Hz,1H,Ar-H),7.70(d,J=16Hz,1H,C=C-H),7.55-7.52(m,1H,Ar-H),7.45(d,J=8.8Hz,1H,C=C-H),7.35(d,J=8.8Hz,1H,Ar-H),7.28(s,1H,Ar-H),7.24-7.16(m,2H,Ar-H),7.11(s,1H,Ar-H),6.66(dd,J1=9.2Hz,J2=3.2Hz,1H,Ar-H),6.50(d,J=2.4Hz,1H,Ar-H),4.78(q,J=18Hz,2H,TB-CH2),4.42(s,2H,-CH2-bridge),4.22(d,J=16.8Hz,2H,TB-CH2),3.14(s,6H,-CH3*2).
核磁共振碳谱:13C NMR(100MHz,CDCl3)δ185.1,161.5,156.9,146.6,145.2,143.1,133.6,130.7,130.6,129.7,129.4,128.4,126.5,125.1,121.8,117.1,115.6,112.3,111.4,110.4,99.5,66.4,57.7,57.4,41.9.
质谱:HRMS(ESI)m/z:calcd for C29H24BrN3O3[M+Na]+:541.1001;found:654.1410.
中间体12参照文献方法合成。将中间体12(2.0mmol)、中间体3(2.2mmol)和三滴哌啶溶解在乙醇(15.0mL)中加热回流48h,反应结束后冷却至室温,减压除去溶剂得到粗产物,通过柱层析纯化(V石油醚:V乙酸乙酯=3:1)得化合物13(0.69g,64%)。
表7产物的合成
Claims (6)
方法(1)
将下式中间体5、中间体3和三滴哌啶溶于无水乙醇中,回流一段,反应结束后冷却至室温,旋干溶剂,粗产物经柱层析纯化得化合物目标产物;
方法(2)
将将下式所示中间体5、中间体4和三滴哌啶溶解在乙醇中加热回流48h,反应结束后冷却至室温,旋干溶剂,粗产物经柱层析纯化得目标产物;
方法(3)
将3-甲氧基-4-溴苯胺8和多聚甲醛加入圆底烧瓶内,置于低温槽中搅拌条件下向烧瓶内缓慢滴加三氟乙酸,之后室温下反应若干天;TLC追踪至反应完全后,将反应物倒入冰水中淬灭,然后用氨水调节pH至9-10,冷却至室温,用二氯甲烷萃取,旋干得粗产物;粗产物中倒入丙酮加热,全部溶解后,置于室温下重结晶,抽滤并用丙酮洗涤,得下式中间体9
将中间体9加入到干净的圆底烧瓶内,抽换气,置于低温槽中搅拌条件下向烧瓶内加入无水四氢呋喃,滴加正丁基锂,反应一段时间后滴加无水DMF,之后置于室温下反应;TLC追踪至反应完全后,用二氯甲烷萃取,旋干得粗产物;粗产物经柱层析提纯得下式所示中间体10
将下式所示中间体5、中间体10和三滴哌啶溶解在乙醇中加热回流,反应结束后冷却至室温,减压除去溶剂得到粗产物,通过柱层析纯化得目标产物
方法(4)
将下式所示中间体12、中间体3和三滴哌啶溶解在乙醇中加热回流,反应结束后冷却至室温,减压除去溶剂得到粗产物,通过柱层析纯化得目标产物
3.权利要求1中所述化合物6、7、11或13在制备高亮度红色固态发光材料中的应用。
4.权利要求1中所述化合物6、7、11或13在检测Fe3+中的应用。
5.权利要求1中所述化合物7在制备抗肿瘤药物中的应用。
6.权利要求1中所述化合物6、7、11或13在制备肿瘤细胞造影剂中的应用。
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