CN108948031B - 2-醛基罗丹明类衍生物的制备方法及其应用 - Google Patents
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Abstract
Description
技术领域
本发明涉及化学合成领域,具体的涉及2-醛基罗丹明类衍生物的制备方法。
背景技术
罗丹明是一类具有优异光学性质的染料,与其他常用的荧光染料相比,罗丹明类荧光染料具有光稳定性好、长波长吸收、吸收系数大、开环形式的高光稳定性、对pH不敏感、较宽的波长范围和较高的荧光量子产率和荧光寿命长等优点。因此被广泛应用在药理学、生理学、分子生物学、细胞生物学、分子遗传学、环境化学、单个分子检测、信息科学、荧光标记、激光染料等方面,是分析化学和生物医药科学在生物技术领域中最常用的荧光染料。
醛是有机化合物中一类重要的衍生物,醛基具有很高的反应活性,可以发生多种化学反应,在有机合成中起着重要作用,可以与许多底物发生反应,构建出各种各样的化合物,因此含有2-醛基罗丹明类化合物是一类重要功能化罗丹明染料。含有2-醛基的罗丹明类化合物将会对在材料、环境和生命等领域中占有重要地位的多功能罗丹明荧光材料的合成产生重要影响。现有技术中,还未见2-醛基罗丹明类衍生物的报道。
发明内容
本发明目的是提供一系列2-醛基罗丹明类衍生物及其制备方法。
本发明采用的技术方案是:2-醛基罗丹明类衍生物,具有如(Ⅰ)所示的结构通式:
其中,
R1=R2=R3=R4=H;
或R1=R4=H,R2=-CH2CH3,R3=-CH3;
或R1=R2=-CH3,R3=R4=H;
或R1=R2=-CH2CH3,R3=R4=H;
或R1和R4一起形成-(CH2)3-,R2和R3一起形成-(CH2)3-。
2-醛基罗丹明类衍生物的制备方法,包括如下步骤:取罗丹明化合物、乙醇胺和无水乙醇,于75-85℃下反应8-12h小时后,冷却至室温,过滤,所得固体溶于四氢呋喃溶液中,加入还原剂,室温下搅拌1-8小时,加水淬灭,二氯甲烷萃取,经柱层析提纯得到2-醛基罗丹明类衍生物。
优选的,上述的2-醛基罗丹明类衍生物的制备方法,所述的罗丹明化合物为罗丹明B,罗丹明6G,四甲基罗丹明TMR,罗丹明110或罗丹明101。
优选的,上述的2-醛基罗丹明类衍生物的制备方法,所述的还原剂为氢化铝锂、三叔丁氧基氢化铝锂、三乙氧基氢化铝锂、二乙氧基氢化铝锂或硼烷。
优选的,上述的2-醛基罗丹明类衍生物的制备方法,按摩尔比,罗丹明化合物:乙醇胺=1:(3-6)。
优选的,上述的2-醛基罗丹明类衍生物的制备方法,按摩尔比,罗丹明化合物:还原剂=1:(1-10)。
本发明的有益效果是:醛是有机化合物中一类重要的衍生物,醛具有很高的反应活性,可以发生多种化学反应,例如:还原反应,氧化反应,加成反应,缩合反应等等,在有机合成中起着重要作用。本发明构建的2-醛基罗丹明类衍生物,其与商品化的罗丹明染料的最大区别在于2位取代基不同--由醛基取代羧基,众所周知羧基罗丹明由于羧基反应类型单一(酰胺化反应),其在荧光材料中的应用主要用于罗丹明螺酰亚胺类荧光探针的设计合成,而本发明构建的2-醛基罗丹明衍生物可以直接与蛋白质上的半胱氨酸残基结合,并对其进行荧光标记;此外,2-醛基罗丹明衍生物还可以作为构建荧光探针的非常有潜力的中间体。
附图说明
图1是实施例1制备的RhB-CHO的高分辨质谱图。
图2是实施例1制备的RhB-CHO的H-NMR谱图。
图3是实施例1制备的RhB-CHO的C-NMR谱图。
图4是实施例1制备的RhB-CHO标记IgY后凝胶电泳谱图。
具体实施方式
本发明,2-醛基罗丹明类衍生物的反应通式如下:
其中,
R1=R2=R3=R4=H;
或R1=R4=H,R2=-CH2CH3,R3=-CH3;
或R1=R2=-CH3,R3=R4=H;
或R1=R2=-CH2CH3,R3=R4=H;
或R1和R4一起形成-(CH2)3-,R2和R3一起形成-(CH2)3-。
2-醛基罗丹明类衍生物的制备方法,包括如下步骤:
称取1摩尔罗丹明类化合物于圆底烧瓶中,加入无水乙醇和3-6倍摩尔量的乙醇胺,75-85℃下加热反应8-12h小时后,冷却至室温,得到浅粉色固体;将浅粉色固体溶于四氢呋喃溶液中,加入1-10倍摩尔量的还原剂,室温下搅拌1-8小时,加水淬灭,二氯甲烷萃取,经柱层析提纯得到2-醛基罗丹明类衍生物。
上述还原剂为氢化铝锂、三叔丁氧基氢化铝锂、三乙氧基氢化铝锂、二乙氧基氢化铝锂或硼烷。
上述罗丹明类化合物为罗丹明B、罗丹明6G、四甲基罗丹明TMR、罗丹明110或罗丹明101。
实施例1 2-醛基罗丹明B的制备方法(RhB-CHO)
于圆底烧瓶中,将1mol的罗丹明B和3mol的乙醇胺加入到干燥的20mL无水乙醇中,80℃油浴反应8-12h,冷却至室温后,过滤,固体物用乙醇洗涤数次,得到浅粉色固体;将浅粉色固体溶于四氢呋喃溶液中,加入10mol氢化铝锂,室温下搅拌1-8小时,将反应液用水淬灭,用二氯甲烷萃取,取有机相,加入无水硫酸镁干燥,经柱层析提纯得到目标产物RhB-CHO。HRMS:427.2386。
实施例2 2-醛基罗丹明6G的制备方法(Rh6G-CHO)
于圆底烧瓶中,将1mol的罗丹明6G与4mol的乙醇胺加入到干燥的20mL无水乙醇中,80℃油浴反应8-12h,冷却至室温后,过滤,固体物用乙醇洗涤数次,得到粉色固体;将粉色固体溶于四氢呋喃溶液中,加入10mol三叔丁氧基氢化铝锂,室温下搅拌1-8小时,将反应液用水淬灭,用二氯甲烷萃取,取有机相,加入无水硫酸镁干燥,经柱层析提纯得到目标产物Rh6G-CHO。HRMS:398.1994。
实施例3 2-醛基四甲基罗丹明TMR的制备方法(TMR-CHO)
于圆底烧瓶中,将1mol的四甲基罗丹明TMR与5mol的乙醇胺加入到干燥的20mL无水乙醇中,80℃油浴反应8-12h,冷却至室温后,过滤,固体物用乙醇洗涤数次,得到粉色固体;将粉色固体溶于四氢呋喃溶液中,加入8mol三乙氧基氢化铝锂,室温下搅拌1-8小时,将反应液用水淬灭,用二氯甲烷萃取,取有机相,加入无水硫酸镁干燥,经柱层析提纯得到目标产物TMR-CHO。HRMS:371.1760。
实施例4 2-醛基罗丹明110的制备方法(Rh110-CHO)
于圆底烧瓶中,将1mol的罗丹明110与6mol的乙醇胺加入到干燥的20mL无水乙醇中,80℃油浴反应8-12h,冷却至室温后,过滤,固体物用乙醇洗涤数次,得到粉色固体;将粉色固体溶于四氢呋喃溶液中,加入5mol二乙氧基氢化铝锂,室温下搅拌1-8小时,将反应液用水淬灭,用二氯甲烷萃取,取有机相,加入无水硫酸镁干燥,经柱层析提纯得到目标产物Rh110-CHO。HRMS:315.1134。
实施例5 2-醛基罗丹明101的制备方法(Rh101-CHO)
于圆底烧瓶中,将1mol的罗丹明101与5mol的乙醇胺加入到干燥的20mL无水乙醇中,80℃油浴反应8-12h,冷却至室温后,过滤,固体物用乙醇洗涤数次,得到粉色固体;将粉色固体溶于四氢呋喃溶液中,加入6mol氢化铝锂,室温下搅拌1-8小时,将反应液用水淬灭,用二氯甲烷萃取,取有机相,加入无水硫酸镁干燥,经柱层析提纯得到目标产物Rh101-CHO。HRMS:475.2386。
实施例6 RhB-CHO对IgY染色标记
取适量IgY溶液,加入三角烧瓶中,再加入生理盐水及碳酸盐缓冲液,使蛋白浓度为20mg/mL,碳酸盐缓冲液容量为总量的1/10,混匀,将三角烧瓶置冰槽中,电磁搅拌(速度适当以不起泡沫为宜)5~10min。取1mg实施例1制备的2-醛基罗丹明衍生物RhB-CHO,加入10mL抗体溶液中,在4℃左右继续搅拌12~18h,通常将装置安放4℃冰箱或冰库中进行。透析后,利用葡聚糖凝胶G-25(或G-50)柱提纯,电泳验证标记效果,如图4所示。由图4可见,IgY的半胱氨酸残基可以被RhB-CHO所标记,分子量大约在分别为60-70KD和22-30KD的轻链和重链均被RhB-CHO所标记。
Claims (1)
1.2-醛基罗丹明类衍生物的制备方法,其特征在于,包括如下步骤:取罗丹明化合物、乙醇胺和无水乙醇,于75-85℃下反应8-12h小时后,冷却至室温,过滤,所得固体溶于四氢呋喃溶液中,加入还原剂,室温下搅拌1-8小时,加水淬灭,二氯甲烷萃取,经柱层析提纯得到2-醛基罗丹明类衍生物;
所述罗丹明化合物为罗丹明6G,四甲基罗丹明TMR,罗丹明110或罗丹明101;
按摩尔比,罗丹明化合物: 乙醇胺=1 : (3-6);
所述的还原剂为氢化铝锂;按摩尔比,罗丹明化合物: 还原剂=1 :(1-10);
所述的2-醛基罗丹明类衍生物具有如(Ⅰ)所示的结构通式:
其中,R1=R2=R3=R4=H;
或R1=R4=H,R2=-CH2CH3,R3=-CH3;
或R1=R2=-CH3,R3=R4=H;
或R1和R4一起形成-(CH2)3-,R2和R3一起形成-(CH2)3-。
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