CN116178472B - 达玛烷型人参皂苷衍生物、制备方法及其应用 - Google Patents
达玛烷型人参皂苷衍生物、制备方法及其应用 Download PDFInfo
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- CN116178472B CN116178472B CN202211693940.4A CN202211693940A CN116178472B CN 116178472 B CN116178472 B CN 116178472B CN 202211693940 A CN202211693940 A CN 202211693940A CN 116178472 B CN116178472 B CN 116178472B
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- ginsenoside
- dammarane
- type ginsenoside
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Abstract
本发明提供一种达玛烷型人参皂苷衍生物、制备方法及其应用;达玛烷型人参皂苷衍生物结构式如下:制备方法包括:将PPD、PPT型人参皂苷中任一种和杂多酸催化剂置于反应容器中,加入甲醇、乙醇、乙腈中任一种的水溶液后水浴加热,磁力搅拌后生成目标产物;反应完成后将反应溶液放置室温后经滤膜过滤得到混合物;经柱层析分离得到目标产物。本发明的优势在于:可通过降低肝细胞焦亡相关因子caspase‑1的表达而减轻高脂血症引发的肝脏损伤;采用相对温和的反应条件转化得到稀有人参皂苷,转化率高,收率高。
Description
技术领域
本发明属于药物化学领域,尤其涉及一种达玛烷型人参皂苷衍生物、制备方法及其应用。
背景技术
人参作为东北的道地药材之一,距今已有两千多年的历史。目前对人参中的有效成分研究集中在皂苷、挥发油、糖类和多肽等,最主要的活性成分为人参皂苷,其具有广泛的药理作用,如抗肿瘤、抗氧化、抗炎、抗疲劳、抗应激、抗衰老、免疫调节、保护中枢神经及心脑血管***等。人参皂苷是由糖和苷元连接形成的糖苷类化合物,根据皂苷元的不同,可分为达玛烷型、克梯隆型和齐墩果酸型。目前从人参中分离鉴定出的人参皂苷达到一百多种,根据其含量高低分为主要人参皂苷和稀有人参皂苷。人参皂苷中含量最丰富的Rb1、Rb2、Rc、Rd等主要皂苷占总皂苷的90%以上。而主要人参皂苷的次级代谢产物稀有人参皂苷,具备更高的生物活性和药理活性,已被广泛应用于临床。
主要人参皂苷与稀有人参皂苷之间的差异主要表现在皂苷元连接的糖基取代基不同。人参皂苷的糖基与其生物活性密切相关,糖基化数量的减少可能会显著提高人参皂苷的生物利用度。
然而,许多稀有人参皂苷在人参中的含量很低甚至不存在,只能由主要人参皂苷转化制备成稀有人参皂苷。从低生物利用度的主要人参皂苷转化生产高生物活性和高生物利用度的稀有人参皂苷(Rg3及其衍生物)是开发天然皂苷和人参类药物的关键。目前转化稀有人参皂苷的方式主要为化学转化和生物转化,化学转化的工艺中,通常以无机或有机酸、碱为催化剂,以纯水作为转化溶剂来转化主要人参皂苷,但存在稀有人参皂苷制备方法复杂或转化时间长、转化率低的问题。
发明内容
针对现有技术中稀有人参皂苷制备方法复杂或转化时间长,转化率低的问题,本发明提供一种达玛烷型人参皂苷衍生物及其制备方法。
本发明的技术方案如下:一种达玛烷型人参皂苷衍生物,分子结构如下式所示:
本发明还提供用于制备上述达玛烷型人参皂苷衍生物的制备方法,包括如下步骤:
S1、将达玛烷型人参皂苷和杂多酸催化剂置于反应容器中,加入加成反应试剂和转化溶剂后水浴加热,磁力搅拌一定时间后生成目标产物;
S2、反应完成后将反应溶液放置室温后经滤膜过滤得到混合物,经柱层析分离得到目标产物;
所述达玛烷型人参皂苷包括:原人参二醇型人参皂苷、原人参三醇型人参皂苷中任一种;所述加成反应试剂和转化溶剂为甲醇、乙醇、乙腈中任一种的水溶液。
进一步地,所述杂多酸催化剂为H3PW12O40、CsxH3-xPW12O40(x=0.5,1.0,1.5,2.0,2.1,2.2,2.3,2.4,2.5,3)中任一种。
进一步地,所述达玛烷型人参皂苷和杂多酸催化剂的比例为1:0.5~1:5。
进一步地,所述有机溶剂在水中的体积比为10%-75%。
优选地,达玛烷型人参皂苷和催化剂的比例优选为1:1,有机溶剂在水中的体积比优选为50%。
进一步地,所述水浴加热温度为40-100℃,磁力搅拌时间为1-4h。
优选地,水浴加热温度优选为80℃,磁力搅拌时间优选为4小时。
进一步地,所述滤膜孔径为0.22μm,0.45μm,0.6μm中任一种。
本发明还保护上述达玛烷型人参皂苷衍生物在抗肝脏损伤方向的应用。
本发明的优势在于:不同于以往报道的以水作为转化溶剂的转化方法,而是采用提供质子的有机溶剂作为转化溶剂,同时也作为反应物与人参皂苷发生加成反应制备获得尚未报道过的人参皂苷衍生物;本发明中的C25位人参皂苷衍生物可能通过降低肝细胞焦亡相关因子caspase-1的表达而减轻高脂血症大鼠肝脏损伤。并且本发明使用的固体杂多酸作为催化剂,在催化效果得到大大提升的同时,反应结束后催化剂可回收再利用;可采用相对温和的反应条件转化得到稀有人参皂苷,转化率高,收率高。
附图说明
图1为以甲醇水溶液为溶剂时人参皂苷Rb1转化为人参皂苷C25-OCH3衍生物的示意图;
图2为以乙醇水溶液为溶剂时人参皂苷Rb1转化为人参皂苷C25-OCH2CH3衍生物的示意图;
图3为以乙腈水溶液为溶剂时人参皂苷Rb1转化为人参皂苷C25-C2H2N衍生物的示意图;
图4为本发明的方法生产得到人参皂苷C25-OCH2CH3衍生物的总离子流图;
图5为肝细胞焦亡相关因子caspase-1蛋白水平对照图。
具体实施方式
下面将对本发明实施例中的技术方案进行清楚、完整地描述,显然,所描述的实施例仅仅是本发明一部分实施例,而不是全部的实施例。基于本发明中的实施例,本领域普通技术人员在没有做出创造性劳动前提下所获得的所有其它实施例,都属于本发明保护的范围。
本发明以有机极性溶剂为反应物化学转化达玛烷型皂苷C24-C25位双键得到的人参皂苷衍生物。该新型的人参皂苷衍生物尚未报道,分别为人参皂苷C25-OCH3衍生物、人参皂苷C25-OCH2CH3衍生物和人参皂苷C25-C2H2N衍生物。
具体人参皂苷C25-OCH3衍生物、人参皂苷C25-OCH2CH3衍生物和人参皂苷C25-C2H2N衍生物,系指具有如下结构特点的人参皂苷衍生物:
上述达玛烷型人参皂苷衍生物是以达玛烷型人参皂苷Rg3为基体,在C25位上的衍生物,人参皂苷Rg3是从人参中分离出来的一种生物活性成分,研究证明人参皂苷Rg3及其C25位衍生物具有明显的抗肿瘤作用,同时还具有抗氧化、神经保护和其他生物活性,可用于辅助化疗。此外,活性皂苷元的发现和结构鉴定可能为开发用于癌症预防和治疗的新化合物提供了机会。高活性的人参皂苷Rg3及其衍生物可以从活性较低的原人参二醇型(PPD)人参皂苷、原人参三醇型(PPT)人参皂苷中转化获得;包括:Rb1、Rb2、Rc等,以人参皂苷Rb1为例,人参皂苷Rb1在人参中含量丰富,其结构可以通过水解C-20位置的糖醛酸键转化为人参皂苷Rg3,对Rb1进行转化,可得到稀有人参皂苷Rg3及其C25位的衍生物。
本发明的实现过程具体为利用甲醇、乙醇等能够提供质子的有机溶剂作为加成反应试剂,与达玛烷型人参皂苷中C24-C25位的双键发生亲电加成反应。其中,有机溶剂亲电部分的质子加成在C24位,剩余的亲核部分加成在C25位,生成人参皂苷C25-OCH3、C25-OCH2CH3,同时本发明还发现以乙腈为溶剂也可得到C25-C2H2N衍生物。
具备包括如下步骤:
S1、将达玛烷型人参皂苷和杂多酸催化剂置于圆底烧瓶中,加入加成反应试剂和转化溶剂后将圆底烧瓶于水浴加热,磁力搅拌一定时间后生成目标产物。
S2、反应完成后将反应溶液放置室温后经滤膜过滤得到混合物;经柱层析分离得到目标产物。
所述达玛烷型人参皂苷包括:原人参二醇型(PPD)人参皂苷、原人参三醇型(PPT)人参皂苷中的任一种。
所述杂多酸催化剂为H3PW12O40、CsxH3-xPW12O40(x=0.5,1.0,1.5,2.0,2.1,2.2,2.3,2.4,2.5,3)。达玛烷型人参皂苷和催化剂的比例为1:0.5~1:5,优选为1:1。
所述加成反应试剂和转化溶剂为有机溶剂甲醇、乙醇、乙腈等的水溶液;有机溶剂在水中的体积比为10%-75%,优选为50%。
所述圆底烧瓶中水浴加热温度为40-100℃,优选为80℃;磁力搅拌时间为1-4h,优选为4小时。
所述滤膜孔径为0.22μm,0.45μm,0.6μm,优选为0.22μm。
本发明提供的制备方法可将达玛烷型人参皂苷转化为人参皂苷C25-OCH3、C25-OCH2CH3和C25-C2H2N衍生物,转化过程参考图1-3。
对得到的目标产物进行通过高效液相色谱-质谱联用进行分析以确定其结构,高效液相色谱-LTQ质谱法操作步骤如下:
高效液相色谱程序中,流动相分别为A相0.1%甲酸水溶液、B相乙腈,色谱纯;梯度洗脱条件(体积分数):0~5min(25%B~30%B),5~8min(30%~36%B),8~15min(36%~48%B),15~20min(48%~70%B),200~25min(70%~90%B),25~28min(90%B),28~34min(25%B)。
流速:0.2mL/min,采用常规C18色谱柱(2.1mm×100mm,1.7μm),柱温35℃,进样量2μL。
质谱条件:质谱仪均配有电喷雾电离源(ESI).负离子扫描模式:毛细管温度320℃,鞘气35arb unit,辅助气10arb unit,吹扫气0arb unit,毛细管电压-3200V。
在不同有机溶剂条件下将人参皂苷Rb1化学转化为Rg3及其C25位衍生物的途径如图1-3所示。首先,C3位的糖基链不发生反应,而Rb1的C20位糖基部分发生水解,生成C20位具备叔醇结构的一对差向异构体20(S)-和20(R)-Rg3,苷元烯烃链进一步发生C24和C25位加成,反应遵循Markovnikov规则,甲氧基与乙氧基加成在含氢原子较少的C25位,生成C25位衍生物。
以人参皂苷C25-OCH2CH3为例,对得到的转化产物进行分析:
利用HPLC-MS分析人参皂苷Rb1的化学转化产物,总离子流图如图4所示。通过与标准品进行比对,可以确定峰1是相对分子质量为1108的反应物人参皂苷Rb1,峰2和峰3的分子量为802,根据其串联质谱图可观察到[M-H]-离子(m/z 801)与Rb1的分子量相差306Da(2×162Da-18Da),表明分子量为802的物质是Rb1的C20位去糖基化反应产物20(S)-和20(R)-25-OH-Rg3。峰4、5、8、9的相对分子质量均为784,是Rb1发生C20位去糖基化反应的产物。通过比较保留时间可以推断,峰4和峰5,以及峰8和峰9分别为结构相近的异构体。
对4种产物的[M-H]-离子进行四级串联质谱分析,发现这些特征碎片离子均由皂苷元离子进一步裂解产生。其中m/z 419离子与其皂苷元离子之间的质量差异为58Da,对应于连接了2个甲基的叔醇结构(C3H6O),故可以推断峰2和峰3发生了C24和C25位的水合反应。当发生碰撞诱导解离时,C24和C25位的单键断裂,脱除C3H6O的叔醇结构,产生58Da的中性丢失,同时,峰4和峰5发生C20位的脱水反应,抵消水合反应产生的+18Da的质量差异。
因此,将峰4和峰5分别归属为25-OH-Rk1和25-OH-Rg5,通过比对标准品的相对保留时间和二级串联谱图,确定峰8和峰9分别为20(S)-Rg3和20(R)-Rg3。峰6和峰7的相对分子质量为830,与m/z为784的物质的分子量相差46,根据其二级串联质谱图可确认其为20(S)-Rg3和20(R)-Rg3在C24和C25位与乙醇的加成产物。
峰10和峰11的相对分子质量为766,其相对保留时间和二级串联谱图与标准品一致,即峰10和峰11分别为Rk1和Rg5。
本发明得到人参皂苷C25-OCH3、C25-OCH2CH3、C25-C2H2N衍生物经实验证实对高脂血症大鼠肝脏损伤的保护作用。
以C25-OCH3人参皂苷衍生物为例,实验方法如下:
选32只SPF级健康SD大鼠,体质量190±20g,适应性喂养2周后,随机分为4组,分别为正常(Control)组、模型(Model)组、C25-OCH3人参皂苷衍生物(C25-OCH3-RD)组和辛伐他汀(Simvastatin)组,每组8只。正常组每日给予基础饲料,模型组、C25-OCH3人参皂苷衍生物组和辛伐他汀组每日给予高脂饲料,自由摄食,饮水不限,单笼饲养,每天12/12h昼夜明暗交替。4周后,模型组、C25-OCH3人参皂苷衍生物组和辛伐他汀组继续高脂饲料喂饲,同时灌胃给药,C25-OCH3人参皂苷衍生物组给予150mg/kg/d,辛伐他汀组给予1.8mg/kg/d,对照组与模型组则给予等体积的生理盐水,每日1次。给药8周后,取肝脏组织液氮保存,用于Western blot检测。
取50mg肝脏组织放入2.0ml研磨管中,加入0.5mL组织裂解液,于高度低温组织研磨仪中充分碾碎,冰上静置30min,12000r/min、4℃离心10min,取上清。利用BCA蛋白定量测定试剂盒对总蛋白进行定量,并调平浓度至1.5μg/μL。样品蛋白:5×蛋白上样缓冲液=4:1的比例混合,煮沸5min使其变性。在泳道中加入10μL的Marker和各组蛋白样品,冰水中120V恒压电泳60min,恒流200mA冰水中湿转60min,转移至PVDF膜,TBST清洗膜,转至含有快速封闭液的容器中于摇床上室温封闭10min。对照marker,把膜上的目的蛋白剪开,加入I抗4℃孵育过夜。TBST洗涤3次,每次10min,加入II抗,室温孵育1h,TBST洗涤3次,每次10min。将膜平铺于暗箱中,ECL发光液孵育1min后进行曝光处理,保存条带,采用Image J图像处理软件计算对应凝胶条带的灰度值,以GAPDH作为内参照,对蛋白条带进行相对定量分析,采用GraphPad Prism 9.0.0进行统计学分析。
如图5所示,与Control组比较,Model组大鼠肝脏组织caspase-1表达显著提高(P<0.01);与model组比较,C25-OCH3-RD组与Simvastatin组大鼠肝脏caspase-1表达显著降低(P<0.01),结果表明C25-OCH3人参皂苷衍生物可能通过降低肝细胞焦亡相关因子caspase-1的表达而减轻高脂血症大鼠肝脏损伤。
以下以具体实施例来进一步说明本发明的人参皂苷C25-OCH3、C25-OCH2CH3、C25-C2H2N衍生物制备方法和条件。
实施例1
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入10%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为94.12%,C25-OCH3衍生物的产率为63.55%。
实施例2
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入30%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为93.89%,C25-OCH3衍生物的产率为73.63%。
实施例3
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为93.83%,C25-OCH3衍生物的产率为75.29%。
实施例4
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化3h,Rb1转化率为92.81%,C25-OCH3衍生物的产率为61.23%。
实施例5
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化2h,Rb1转化率为87.72%,C25-OCH3衍生物的产率为38.99%。
实施例6
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化1h,Rb1转化率为84.98%,C25-OCH3衍生物的产率为20.02%。
实施例7
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:0.5,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为76.29%,C25-OCH3衍生物的产率为56.83%。
实施例8
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:5,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为93.91%,C25-OCH3衍生物的产率为75.41%。
实施例9
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:5,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化3h,Rb1转化率为93.05%,C25-OCH3衍生物的产率为61.42%。
实施例10
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:5,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化2h,Rb1转化率为87.96%,C25-OCH3衍生物的产率为39.16%。
实施例11
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:5,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化1h,Rb1转化率为85.14%,C25-OCH3衍生物的产率为20.23%。
实施例12
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为60℃,磁力搅拌转化4h,Rb1转化率为86.26%,C25-OCH3衍生物的产率为67.97%。
实施例13
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为50℃,磁力搅拌转化4h,Rb1转化率为61.33%,C25-OCH3衍生物的产率为44.53%。
实施例14
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入75%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为93.47%,C25-OCH3衍生物的产率为78.98%。
实施例15
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入10%乙醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为81.02%,C25-OCH2CH3衍生物的产率为63.23%。
实施例16
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入30%乙醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为79.87%,C25-OCH2CH3衍生物的产率为65.89%。
实施例17
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%乙醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为75.64%,C25-OCH2CH3衍生物的产率为62.72%。
实施例18
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入75%乙醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为63.35%,C25-OCH2CH3衍生物的产率为58.05%。
实施例19
称取人参皂苷Rb2和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb2转化率为93.84%,C25-OCH3衍生物的产率为73.62%。
实施例20
称取人参皂苷Rb3和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb3转化率为91.58%,C25-OCH3衍生物的产率为74.90%。
实施例21
称取人参皂苷Rc和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rc转化率为93.52%,C25-OCH3衍生物的产率为72.18%。
实施例22
称取人参皂苷Rb1和Cs2H1PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为74.22%,C25-OCH3衍生物的产率为53.68%。
实施例23
称取人参皂苷Rb1和H3PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入50%甲醇水溶液后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化4h,Rb1转化率为94.33%,C25-OCH3衍生物的产率为72.28%。
对比例1
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入去离子水后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化1h,Rb1转化率为89.16%,C25-OCH3衍生物的产率为0。
对比例2
称取人参皂苷Rb1和Cs1H2PW12O40催化剂后置于圆底烧瓶中,皂苷和催化剂的比例为1:1,加入去离子水后将圆底烧瓶中水浴加热,水浴温度为80℃,磁力搅拌转化2h,Rb1转化率为93.03%,C25-OCH3衍生物的产率为0。
以上所述仅是本发明的较佳实施例而已,并非对本发明作任何形式上的限制,虽然本发明已以较佳实施例揭露如上,然而并非用以限定本发明,任何熟悉本专利的技术人员在不脱离本发明技术方案范围内,当可利用上述提示的技术内容作出些许更动或修饰为等同变化的等效实施例,但凡是未脱离本发明技术方案的内容,依据本发明的技术实质对以上实施例所作的任何简单修改、等同变化与修饰,均仍属于本发明方案的范围内。
Claims (9)
1.一种达玛烷型人参皂苷衍生物,其特征在于,分子结构如下式所示:
。
2.一种达玛烷型人参皂苷衍生物的制备方法,其特征在于,用于制备如权利要求1所述的达玛烷型人参皂苷衍生物,包括如下步骤:
S1、将达玛烷型人参皂苷和杂多酸催化剂置于反应容器中,加入加成反应试剂和转化溶剂后水浴加热,磁力搅拌一定时间后生成目标产物;
S2、反应完成后将反应溶液放置室温后经滤膜过滤得到混合物,经柱层析分离得到目标产物;
所述达玛烷型人参皂苷包括:原人参二醇型人参皂苷、原人参三醇型人参皂苷中任一种;所述加成反应试剂和转化溶剂为有机溶剂甲醇、乙醇中任一种的水溶液;所述杂多酸催化剂为H3PW12O40、CsxH3-xPW12O40中任一种,其中x=0.5,1.0,1.5,2.0,2.1,2.2,2.3,2.4,2.5,3中任一种。
3.根据权利要求2所述的达玛烷型人参皂苷衍生物的制备方法,其特征在于:所述达玛烷型人参皂苷和杂多酸催化剂的比例为1:0.5~1:5。
4.根据权利要求2所述的达玛烷型人参皂苷衍生物的制备方法,其特征在于:所述有机溶剂甲醇、乙醇在水中的体积比为10%-75%。
5.根据权利要求3或4所述的达玛烷型人参皂苷衍生物的制备方法,其特征在于:达玛烷型人参皂苷和催化剂的比例为1:1,有机溶剂在水中的体积比为50%。
6.根据权利要求2所述的达玛烷型人参皂苷衍生物的制备方法,其特征在于:所述水浴加热温度为40-100℃,磁力搅拌时间为1-4h。
7.根据权利要求6所述的达玛烷型人参皂苷衍生物的制备方法,其特征在于:所述水浴加热温度为80℃,磁力搅拌时间为4小时。
8.根据权利要求2所述的达玛烷型人参皂苷衍生物的制备方法,其特征在于:所述滤膜孔径为0.22μm,0.45μm,0.6μm中任一种。
9.一种如权利要求1所述的达玛烷型人参皂苷衍生物在制备抗肝脏损伤药物方向的用途。
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