CN105061545A - 文冠果中三萜皂苷类化合物及其制备方法和应用 - Google Patents
文冠果中三萜皂苷类化合物及其制备方法和应用 Download PDFInfo
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Abstract
本发明属于医药技术领域,公开了13种新的齐墩果烷型五环三萜类化合物以及6种具有齐墩果烷型五环三萜类化合物的结构和制备方法,一种文冠果果壳、果柄提取物的提取方法,以及上述化合物及提取物在抑制人脑胶质瘤、人肝癌、人胰腺癌、人胃癌、人结肠癌中的应用。本发明公开的有抗癌活性的化合物及提取物可从文冠果果壳、果柄及其他无患子科植物中提取,或从其他生物资源中提取,也可通过化学合成方法得到。
Description
技术领域
本发明属于医药技术领域,涉及文冠果中的一类新皂苷化合物、制备方法及其在抗人脑胶质瘤、人结肠癌、人肝癌人胰腺癌及人胃癌领域中的应用。
背景技术
文冠果(XanthocerassorbifoliaBunge)为无患子科(Sapindaceae)文冠果属植物,别名温革旦子、僧灯毛道、崖木瓜等,单属单种。分布于我国东北、华北、陕西、甘肃、宁夏、安徽、河南等地的丘陵山坡处。经研究,从文冠果果壳、果柄、花及其他部位分离得到的皂苷成分不仅具有良好的抗肿瘤活性,而且能显著改善多种记忆障碍模型小鼠的学习能力,提高大脑的缺氧耐受能力,预防并治疗多发性栓塞引起的记忆保持障碍,降低谷氨酸造成的PC12细胞死亡数量,增强对神经细胞的保护作用。(1.李占林,李铣,李宁,李文,沙沂.文冠果果壳的化学成分.沈阳药科大学学报2005,22(4):271-272;2.刘新霞,纪雪飞,陆玲玲,杨柏珍,王力华,邹莉波,文冠果果壳乙醇提取物对大鼠学习记忆障碍的改善作用.中草药2007,38(12):1859-1863.)。
近年来,很多研究人员对文冠果的化学成分及活性进行了研究,发现其三萜皂苷类化合物具有很好的抗肿瘤活性,其化学成分和药理活性研究公开了以下论文。
1.Yu,L.L.;TAng,X.L.;Chen,L.X.;WAngM.M.;Jian,J.F.;Cao,S.J.;WAng,X.B.;KAng,N.;Qiu,F.Oleanane-typetriterpenoidsaponinsfromXanthocerassorbifoliaBunge.Fitoterapia.2012,83,1636.
2.Yu,L.L.,WAng,X.B.;Wei,X.C.;WAng,M.M.;Chen,L.X.;Cao,S.J.;KAng,N.;Qiu,F.TriterpenoidsaponinsfromXanthocerassorbifoliaBungeandtheirinhibitoryactivityonhumancancercelllines.Bio.&Med.CHem.Let.2012,22,5232.
3.Guo,Y.;Dou,D.Q.;KAng,T.G.;WAng,S.C.;KAng,H.X.StructureelucidationandcompleteNMRspectralassignmentsoftwonewoleanane-typepentacyclictriterpenoidsaponinsfromthehusksofXanthocerassorbifoliaBunge.Magn.Reason.Chem.2009,47,982.
4.Cui,H.;Xiao,H.;Ran,X.K.;Li,Y.Y.;Dou,D.Q.;KAng,T.G.Twonewoleanane-typepentacyclictriterpenoidsaponinsfromthehusksofXanthocerassorbifoliaBunge.J.AsianNat.Prod.Res.2012,14,216.
5.Li,Y.Y.;XiAng,Z.;Cui,H.;Xiao,H.;KAng,T.G.;Dou,D.Q.;KuAng,H.X.Twonewoleanane-typesaponinsfromthehusksofXanthocerassorbifoliaBunge.Nat.Prod.Res.2013,27,208.
6.Li,Z.L.;Li,D.Y.;He,X.M.;Hua,H.M.TwonewtriterpenoidsaponinsfromthehusksofXanthocerassorbifolia.Nat.Prod.Res.2013,27,232.
在对文冠果化学成分研究中我们发现其果皮、果柄中富含皂苷,但其果皮、果柄一直作为废弃物未能得到开发利用,为了变废为宝、提高文冠果的综合利用价值,我们对文冠果果壳、果柄的化学成分进行了系统的分离,并对所得浸膏及化合物的活性进行了系统的筛选、考察。
齐墩果烷型五环三萜皂苷是文冠果果壳、果柄的主要药效成分,而现阶段从文冠果果壳、果柄提取物中分离得到的皂苷类化合物主要为具有齐墩果烯骨架的五环三萜皂苷。该类型三萜皂苷母核结构包含barrigenolR1,barrigenolA1,barrigenolA2,barrintogenolC和16-deoxybarringtogenolC,该母核结构在无患子科植物中有较多发现。
为了将文冠果的药用价值发挥到最大,我们对文冠果果壳、果柄的成分进行了系统的成分研究,发现了新的三萜皂苷以及已知文冠果皂苷的新活性,并利用核磁共振、质谱、红外、紫外等手段对化合物的结构进行了确证。
为了研究文冠果中的三萜成分的抗肿瘤活性,我们对其提取物、单体成分进行了常见的人体癌症细胞的活性测试,包括人脑胶质瘤、人结肠癌、人肝癌、人胰腺癌和人胃癌在内的细胞被用来研究上述化合物和浸膏的抑制活性。
发明内容
本发明的目的在于提供新的齐墩果烯五环三萜皂苷类化合物。
其中,R1可以为当归酰基、环氧当归酰基或者双当归酰基取代的呋糖基;R2可以为当归酰基、乙酰基或者2-甲基丁酰基;R3为三糖基或者双糖基取代;R4为羟基或者乙酰基;R5为羟基或者氢;R6为甲基或者羟甲基;R7为单糖基、双糖基、三糖基、当归酰基取代的糖基、正丁酯基取代的糖基、甲酯基取代的糖基取代。
其优选包括13种新化合物,其结构如表中*标记的化合物结构。
本发明的另一目的是提供了包含所述的13种新化合物在内的共19种化合物的良好的抑制肿瘤细胞活性,包括人脑胶质瘤细胞株(U87-MG)、人肝癌细胞株(HepG-2)、人胰腺癌细胞株(PANC-1)、人胃癌细胞株(NCI-N87)、人结肠癌细胞株(Colo-320DM)。
本发明所提供的19种化合物的结构、名称如下,其中有*标记的为新结构:
化合物1:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-吡喃葡萄糖醛酸基-21,22-二-O-当归酰基-R1-barrigenol
化合物2:3-O-β-D-吡喃葡萄糖基-28-O-(2″-O-α-L-吡喃鼠李糖基)-β-D-吡喃葡萄糖基-16-deoxybarringtogenol
化合物3:3-O-(6′-O-β-D-吡喃葡萄糖基-3′-O-当归酰基)-β-D-吡喃葡萄糖基-28-O-(6″-O-β-D-吡喃葡萄糖基-2″-O-α-L-吡喃鼠李糖基)-β-D-吡喃葡萄糖基-16-deoxybarringtogenol)
化合物4:3-O-(6′-O-β-D-吡喃葡萄糖基-3′-O-当归酰基)-β-D-吡喃葡萄糖基-28-O-(2″-O-α-L-吡喃鼠李糖基)-β-D-吡喃葡萄糖基-16-deoxybarringtogenol
化合物5:16-deoxybarringtogenol
化合物6:3-O-(2′-O-β-D-吡喃半乳糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-21,22-二-O-当归酰基-R1-barrigenol
化合物7:21,22-二-O-当归酰基-R1-barrigenol
化合物8:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃葡萄糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-21-O-(3″″,4″″-二-O-当归酰基)-β-D-吡喃呋糖基-22-O-乙酰基-barringtogenolC
化合物9:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃葡萄糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21-O-(3″″,4″″-二-O-当归酰基)-β-D-吡喃呋糖基-22-O-乙酰基-barringtogenolC
化合物10:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃葡萄糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-16-O-乙酰基-21,22-O-二-当归酰基-barringtogenolC
化合物11:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21-O-环氧化当归酰基-22-O-当归酰基-barringtogenolC
化合物12:3-O-(3′-O-当归酰基)-β-D-吡喃葡萄糖基-28-O-(2″-O-α-L-吡喃鼠李糖基)-β-D-吡喃葡萄糖基-16-deoxy-barringtogenolC
化合物13:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21-O-(3″″,4″″-二-O-当归酰基)-α-L-吡喃鼠李糖基-22-O-乙酰基-barringtogenolC
化合物14:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21,22-二-O-当归酰基-R1-barrigenol
化合物15:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21,22-二-O-当归酰基-barringogenolC
化合物16:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-24-羟基-21,22-二-O-当归酰基-R1-barrigenol
化合物17:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-24-羟基-21,22-二-O-当归酰基-R1-barrigenol
化合物18:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-24-羟基-21,22-二-O-当归酰基-barringogenolC
化合物19:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21-O-当归酰基-22-O-(2-甲基)-丁酰基-R1-barrigenol
上述化合物及其盐可以作为制备抗肿瘤药物的应用。
本发明的另一目的在于提供了所述19种化合物的制备方法。包括以下操作步骤,采用文冠果果壳、果柄等为原料,用有机溶剂或含水醇、盐溶液制备提取物,再进行对化合物的分离。
具体通过如下方法制备:
(1)提取方法1:取干燥文冠果果壳、果柄,粉碎,然后按重量体积比1:2-1:8加入50%-70%乙醇,回流提取1-3次,每次0.5-4h。所得提取液经减压回收溶剂浓缩,浓缩液分别用1-5倍体积的乙酸乙酯、正丁醇萃取1-5次,正丁醇萃取物为提取物1-5次,应用硅胶柱色谱对提取物1进行分离,用二氯甲烷:甲醇:水30:1:1~1:1:1进行梯度洗脱,所得流分可经薄层检识后合并,所得流分应用中低压或HPLC色谱制备分离,以甲醇:水(10:90~100:0)或乙腈:水(10:90~100:0)进行梯度洗脱制备的化合物,或流份以反复硅胶柱色谱法,以氯仿-甲醇或二氯甲烷-甲醇(100:0~0:100)为流动相梯度洗脱,所得流分经薄层检识后合并,流分再用SephadexLH-20脱色素,以甲醇/水为流动相,分离制备得到化合物。
(2)提取方法2:取干燥文冠果果壳、果柄粉碎,然后按照重量体积比1:2-1:8加入50%-70%乙醇,回流提取1-3次,每次0.5-4h,所得提取液经减压回收溶剂浓缩,浓缩液离心去除沉淀,上清液经大孔树脂AB-8分离纯化,以乙醇-水(0%,10%,30%,50%,80%,95%)为溶剂进行梯度洗脱,收集30-80%乙醇提取物,即得提取物2。提取物2经过上述提取1相似的综合色谱分离方法,制备得到单体化合物。
所述有机溶剂为甲醇、乙醇、丙酮、正丁醇、乙酸乙酯、石油醚、氯仿、二氯甲烷中的一种或几种。所述提取温度在于30-100℃,提取时间0.5-4小时;所述分离方法为综合色谱分离法。
本发明相对现有技术具有如下优点及效果:(1)提供了一系列的新三萜皂苷类化合物。(2)运用活性评价方法对新结构及已知结构在内的1-19化合物进行了抗癌活性评价,所述的化合物对多种人源肿瘤有很好的抑制活性。
具体实施方式
为了使本发明的目的及优点更加清楚明白,以下结合实施例对本发明进行进一步详细说明。应当理解,此处所描述的具体实施例仅仅用以解释本发明,并不用于限定本发明。
实施例1文冠果果壳、果柄提取物1的制备方法。
取干燥文冠果果壳、果柄7kg(2011年采于内蒙古赤峰市),粉碎,然后按照重量体积比1:8加入70%乙醇,回流提取3次,每次2h。所得提取液经减压回收溶剂浓缩。浓缩液依次用等体积的乙酸乙酯和正丁醇萃取3次,得文冠果果壳、果柄正丁醇萃取物,除去溶剂,所得棕色提取物即为提取物1(350g)。
实施例2:文冠果果壳、果柄提取物2的制备方法。
取干燥文冠果果壳、果柄7kg(2011年采于内蒙古赤峰市),粉碎,然后按照重量体积比1:8加入70%乙醇,回流提取3次,每次2h。所得提取液经减压回收溶剂浓缩。浓缩液经大孔树脂(AB-8)分离纯化,以乙醇-水为溶剂进行梯度洗脱,收集30%-80%乙醇提取物,所得淡黄色粉末既为提取物2(250g)。
实施例3:从文冠果果壳、果柄中分离齐墩果烯五环三萜皂苷类化合物。
取干燥文冠果果壳、果柄(2011年9月采于内蒙古赤峰)9kg,按实施例1中提取物的制备方法,用70%乙醇回流提取3次,料液比1:8,每次2h,减压回收溶剂,浓缩至10L。分别用等体积的乙酸乙酯和正丁醇萃取3次,得乙酸乙酯萃取物90g,正丁醇萃取物450g。
取正丁醇萃取物450g,用硅胶开放柱色谱以二氯甲烷:甲醇:水(50:1:1-1:1:1)为流动相进行梯度洗脱,所得流份以硅胶薄层色谱为指导合并相同流份,得流份1-5。
取流份1(二氯甲烷:甲醇:水45:1:1)45g,用硅胶开放柱色谱以三氯甲烷:甲醇(30:1-1:1)为流动相梯度洗脱,收集30:1流份,用十八烷基键合硅胶为填料的制备型高效液相色谱柱制备,得化合物16,色谱条件为甲醇:水(82:18);收集20:1流份,用十八烷基键合硅胶快速色谱,以甲醇:水(50:50-100:0)为流动相梯度洗脱,其中甲醇:水(70:30)部分流份用十八烷基键合硅胶为填料的制备型高效液相色谱柱制备,得化合物14、化合物16,色谱条件为甲醇:水(83:17),甲醇:水(85:15)部分流份用十八烷基键合硅胶为填料的制备型高效液相色谱柱制备,得化合物18、19,色谱条件为甲醇:水(78:22);收集10:1流份,用Sephadex-LH20开放柱色谱处理,以甲醇为流动相等度洗脱,所得白色粉末用十八烷基键合硅胶为填料的制备型高效液相色谱柱制备,得化合物13、化合物15,色谱条件为甲醇:水(80:20)。
取流份2(二氯甲烷:甲醇:水35:1:1)20g,用硅胶开放柱色谱以三氯甲烷:甲醇(10:1-1:1)为流动相进行梯度洗脱,收集三氯甲烷:甲醇5:1的流份,此部分流份为淡黄色粉末,将其用SephadexLH-20开放柱色谱处理,以二氯甲烷:甲醇(3:7)为流动相进行等度洗脱,可得白色粉末,再经制备型高效液相,用十八烷基键合硅胶为填料的制备型高效液相色谱柱制备,可得化合物2、化合物5、化合物7,色谱条件为甲醇:水(85:15)。
取流份3(二氯甲烷:甲醇:水25:1:1)80g,用十八烷基键合硅胶快速色谱,以甲醇:水(50:50-100:0)为流动相进行梯度洗脱,收集甲醇:水(75:25)流份,用甲醇进行重结晶,可得化合物1,将重结晶剩余部分用制备型高效液相,用十八烷基键合硅胶为填料的制备型高效液相色谱柱制备,可得化合物8、化合物10、化合物11、化合物12,色谱条件为甲醇:水(60:40)。
取流份4(二氯甲烷:甲醇:水15:1:1)40g,用大孔树脂(D101)开放柱色谱,以乙醇:水(10:90-100:0)为流动相进行梯度洗脱,收集乙醇:水(70:0)流份,此部分流份为淡黄色粉末,将其用十八烷基键合硅胶快速色谱,以甲醇:水(30:70-100:0)为流动相进行梯度洗脱,收集甲醇:水(65:35)部分流份,
将此部分流份用制备型高效液相,用十八烷基键合硅胶为填料的制备型高效液相色谱柱制备制备,可得化合物3、化合物4、化合物6、化合物9,色谱条件为甲醇:水(75:25)。
化合物1:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-吡喃葡萄糖醛酸基-21,22-二-O-当归酰基-R1-barrigenol
白色针晶(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(400MHz,pridine-d5):δ3.27(1H,dd,J=11.6,4.6Hz,H-3),5.51(1H,brs,H-12);C-3-GlcUA:4.90(1H,d,J=7.6Hz,H-1′);C-2′-Gal:5.36(1H,d,J=7.7Hz,H-1″);C-3′-Ara:6.06(1H,d,J=2.0Hz,H-1″′).13CNMR(100MHz,pridine-d5):δ:39.4(C-1),26.4(C-2),89.6(C-3),38.6(C-4),55.3(C-5),18.5(C-6),36.1(C-7),40.7(C-8),46.8(C-9),36.7(C-10),23.7(C-11),125.1(C-12),143.4(C-13),47.4(C-14),67.2(C-15),73.1(C-16),48.1(C-17),41.2(C-18),46.6(C-19),36.5(C-20),78.3(C-21),73.3(C-22),27.6(C-23),16.5(C-24),15.5(C-25),17.3(C-26),21.0(C-27),62.8(C-28),29.2(C-29),19.9(C-30),104.9(C-3-GlcUA-1′),78.6(C-2′),86.1(C-3′),71.5(C-4′),77.0(C-5′),172.0(C-6′),104.6(C-2′-Gal-1″),73.2(C-2″),74.9(C-3″),69.5(C-4″),76.4(C-5″),61.5(C-6″),110.9(C-3′-Ara-1″′),83.3(C-2″′),77.3(C-3″′),85.2(C-4″′),62.0(C-5″′),167.4(C-21-Ang-1),128.6(C-21-Ang-2),137.1(C-21-Ang-3),15.6(C-21-Ang-4),20.7(C-21-Ang-5),167.8(C-22-Ang-1),128.8(C-22-Ang-2),136.2(C-22-Ang-3),15.4(C-22-Ang-4),20.4(C-22-Ang-5).
化合物2:3-O-β-D-吡喃葡萄糖基-28-O-(2″-O-α-L-吡喃鼠李糖基)-β-D-吡喃葡萄糖基-16-deoxybarringtogenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(400MHz,pridine-d5):δ3.38(1H,dd,J1=4.6Hz,J2=11.6Hz,H-3),5.54(1H,brs,H-12);C-3-Glc:4.93(1H,d,J=7.8Hz,H-1′);C-28-Glc:4.73(1H,d,J=7.5Hz,H-1″);C-2′-Rha:6.61(1H,brs,H-1″′).13CNMR(100MHz,pridine-d5):δ39.5(C-1),26.3(C-2),88.5(C-3),39.0(C-4),55.4(C-5),19.4(C-6),32.6(C-7),39.8(C-8),47.6(C-9),36.6(C-10),23.7(C-11),123.5(C-12),142.9(C-13),41.6(C-14),26.0(C-15),18.2(C-16),42.9(C-17),41.9(C-18),46.1(C-19),36.1(C-20),76.6(C-21),72.6(C-22),28.0(C-23),16.5(C-24),15.5(C-25),16.8(C-26),25.5(C-27),74.5(C-28),30.1(C-29),18.4(C-30),106.6(C-3-glc-1′),74.5(C-2′),78.0(C-3′),71.5(C-4′),78.5(C-5′),62.4(C-6′),103.3(C-28-glc-1″′),80.0(C-2″′),75.6(C-3″′),71.6(C-4″′),77.6(C-5″′),62.7(C-6″′),100.3(C-2″′-Rha-1″″),72.3(C-2″″),72.0(C-3″″),74.1(C-4″″),68.8(C-5″″),18.7(C-6″″).
化合物3:3-O-(6′-O-β-D-吡喃葡萄糖基-3′-O-当归酰基)-β-D-吡喃葡萄糖基-28-O-(6″-O-β-D-吡喃葡萄糖基-2″-O-α-L-吡喃鼠李糖基)-β-D-吡喃葡萄糖基-16-deoxybarringtogenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(400MHz,pridine-d5):δ3.30(1H,dd,J=4.2Hz,11.5Hz,H-3),5.39(1H,brs,H-12);C-3-Glc:4.87(1H,d,J=7.8Hz,H-1′);C-6′-glc:5.11(1H,d,J=7.7Hz,H-1″);C-28-glc:4.74(1H,overlapped,H-1″′);C-2″′-Rha:6.54(1H,brs,H-1″″);C-6″′-glc:5.04(1H,d,J=7.74Hz,H-1″″′).13CNMR(100MHz,pridine-d5):δ38.9(C-1),26.7(C-2),89.4(C-3),36.5(C-4),55.7(C-5),18.5(C-6),32.7(C-7),40.3(C-8),48.0(C-9),36.9(C-10),24.0(C-11),123.9(C-12),143.1(C-13),42.1(C-14),26.3(C-15),18.3(C-16),43.3(C-17),41.7(C-18),46.5(C-19),36.3(C-20),76.8(C-21),75.1(C-22),28.2(C-23),16.9(C-24),16.0(C-25),17.0(C-26),25.9(C-27),75.9(C-28),30.5(C-29),20.8(C-30),103.7(C-3-glc-1′),73.4(C-2′),79.3(C-3′),69.6(C-4′),76.5(C-5′),70.2(C-6′),105.6(C-6′-glc-1″),75.2(C-2″),78.4(C-3″),71.6(C-4″),78.1(C-5″),62.7(C-6″),168.1(C-3′-Ang-1),129.0(C-3′-Ang-2),137.0(C-3′-Ang-3),20.8(C-3′-Ang-4),16.0(C-3′-Ang-5),106.8C-28-glc-1″′),80.0(C-2″′),75.5(C-3″′),71.7(C-″′),76.9(C-5″′),70.0(C-6″′),100.9(C-2″′-Rha-1″″),72.5(C-2″″),72.5(C-3″″),74.3(C-4″″),69.3(C-5″″),19.0(C-6″″),105.7(C-6″′-glc-1″″′),75.2(C-2″″′),78.4(C-3″″′),71.6(C-4″″′),78.4(C-5″″′),62.7(C-6″″′).
化合物4:3-O-(6′-O-β-D-吡喃葡萄糖基-3′-O-当归酰基)-β-D-吡喃葡萄糖基-28-O-(2″-O-α-L-吡喃鼠李糖基)-β-D-吡喃葡萄糖基-16-deoxybarringtogenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(400MHz,pridine-d5):δ3.30(1H,dd,J=11.5,4.2Hz,H-3),5.39(1H,brs,H-12);C-3-Glc:4.87(1H,d,J=7.8Hz,H-1′);C-6′-glc:5.11(1H,d,J=7.7Hz,H-1″);C-28-glc:4.74(1H,overlapped,H-1″′);C-2″′-Rha:6.54(1H,brs,H-1″″);C-6″′-glc:5.04(1H,d,J=7.74Hz,H-1″″′).13CNMR(100MHz,pridine-d5):δ39.5(C-1),25.5(C-2),89.0(C-3),38.5(C-4),55.4(C-5),18.7(C-6),32.5(C-7),40.0(C-8),47.6(C-9),36.6(C-10),23.7(C-11),123.5(C-12),142.9(C-13),41.7(C-14),26.3(C-15),18.4(C-16),42.9(C-17),41.0(C-18),46.2(C-19),36.1(C-20),76.5(C-21),75.5(C-22),27.8(C-23),16.7(C-24),15.7(C-25),16.5(C-26),26.0(C-27),74.5(C-28),30.2(C-29),19.4(C-30),106.5(C-3-glc-1′),73.2(C-2′),79.0(C-3′),69.4(C-4′),76.5(C-5′),69.7(C-6′),105.3(C-6′-glc-1″),74.9(C-2″),78.2(C-3″),71.5(C-4″),78.1(C-5″),62.4(C-6″),167.8(C-3′-Ang-1),128.7(C-3′-Ang-2),136.6(C-3′-Ang-3),20.5(C-3′-Ang-4),15.5(C-3′-Ang-5),103.3(C-28-glc-1″′),80.0(C-2″′),74.7(C-3″′),71.3(C-4″′),77.6(C-5″′),62.4(C-6″′),100.3(C-2″′-Rha-1″″),72.3(C-2″″),72.0(C-3″″),74.7(C-4″″),68.8(C-5″″),18.2(C-6″″).
化合物5:16-deoxybarringtogenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):δ3.47(1H,dd,J=11.1,5.1Hz,H-3),5.3122(1H,t,J=3.3Hz,H-12),4.37(1H,d,J=10.0Hz,H-21),3.83(1H,d,J=9.9Hz,H-22).13CNMR(150MHz,pridine-d5):δ39.1(1),28.1(C-2),78.0(C-3),39.3(C-4),55.7(C-5),18.7(C-6),32.9(C-7),40.1(C-8),47.9(C-9),37.2(C-10),23.8(C-11),123.1(C-12),143.7(C-13),41.9(C-14),25.7(C-15),17.8(C-16),43.4(C-17),42.2(C-18),46.7(C-19),36.4(C-20),76.7(C-21),76.8(C-22),28.7(C-23),16.5(C-24),15.7(C-25),16.8(C-26),26.2(C-27),67.9(C-28),30.3(C-29),19.1(C-30).
化合物6:3-O-(2′-O-β-D-吡喃半乳糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-21,22-二-O-当归酰基-R1-barrigenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):δ5.55(1H,brs,H-12),C-3-glcU:5.03(1H,d,7.6Hz,H-1′);C-2′-Gal:5.21(1H,d,7.7Hz,H-1″),13CNMR(150MHz,pridine-d5):δ38.9(C-1),26.6(C-2),89.1(C-3),39.5(C-4),55.5(C-5),18.7(C-6),36.3(C-7),40.9(C-8),47.1(C-9),36.9(C-10),23.9(C-11),125.4(C-12),143.7(C-13),47.7(C-14),67.5(C-15),73.5(C-16),48.3(C-17),41.4(C-18),46.8(C-19),36.7(C-20),78.6(C-21),73.3(C-22),28.0(C-23),16.7(C-24),15.6(C-25),17.5(C-26),21.2(C-27),63.1(C-28),29.5(C-29),20.2(C-30),105.3(C-3-glcU-1′),83.7(C-2′),77.4(C-3′),72.8(C-4′),76.9(C-5′),169.6(C-6′),52.1(C-6′-OCH3),107.1(C-2′-glc-1″),74.6(C-2″),74.9(C-3″),69.5(C-4″),76.7(C-5″),61.2(C-6″),167.7(C-21-Ang-1),128.9(C-21-Ang-2),136.4(C-21-Ang-3),15.8(C-21-Ang-4),20.6(C-21-Ang-5),168.1(C-22-Ang-1),129.1(C-22-Ang-2),137.4(C-22-Ang-3),15.9(C-22-Ang-4),21.0(C-22-Ang-5),
化合物7:21,22-二-O-当归酰基-R1-barrigenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):δ3.14(1H,brs,H-3),5.59(1H,t,J=3.4Hz,H-12),6.74(1H,d,J=10.3Hz,H-21),6.63(1H,d,J=10.3Hz,H-22).13CNMR(150MHz,pridine-d5):δ39.1(C-1),27.9(C-2),78.1(C-3),39.0(C-4),55.3(C-5),18.9(C-6),36.6(C-7),40.8(C-8),47.5(C-9),37.0(C-10),23.8(C-11),125.2(C-12),143.4(C-13),47.0(C-14),67.3(C-15),73.3(C-16),48.1(C-17),41.3(C-18),46.6(C-19),36.1(C-20),78.3(C-21),73.1(C-22),28.4(C-23),16.4(C-24),15.7(C-25),17.4(C-26),20.9(C-27),62.9(C-28),29.2(C-29),20.0(C-30),167.4(C-21-Ang-1),128.6(C-21-Ang-2),136.1(C-21-Ang-3),15.4(C-21-Ang-4),20.3(C-21-Ang-5),167.9(C-22-Ang-1),128.8(C-22-Ang-2),137.1(C-22-Ang-3),15.6(C-22-Ang-4),20.7(C-22-Ang-5).
化合物8:3-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-21-O-(3″″,4″″-二-O-当归酰基)-β-D-吡喃呋糖基-22-O-乙酰基-barringtogenolC
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):δ3.14(1H,dd,J=11.6,4.6Hz,H-3),5.40(1H,brd,H-12),C-3-GlcUA:4.83(1H,d,J=7.6Hz,H-1′);C-2′-Gal:5.30(1H,d,J=7.7Hz,H-1″);C-3′-Ara:5.98(1H,d,J=2.2Hz,H-1″′);C-21-Fuc:4.92(1H,d,J=7.7Hz,H-1″″).13CNMR(150MHz,pridine-d5):δ38.7(C-1),26.4(C-2),89.9(C-3),39.6(C-4),55.7(C-5),20.1(C-6),33.0(C-7),40.3(C-8),46.9(C-9),37.0(C-10),23.8(C-11),123.5(C-12),142.8(C-13),41.7(C-14),34.7(C-15),66.3(C-16),46.6(C-17),39.9(C-18),47.6(C-19),36.7(C-20),92.1(C-21),70.9(C-22),27.4(C-23),16.6(C-24),15.5(C-25),16.9(C-26),27.8(C-27),61.7(C-28),29.7(C-29),18.3(C-30),105.0(C-3-GlcUA-1′),78.6(C-2′),85.9(C-3′),71.2(C-4′),76.2(C-5′),170.0(C-6′),52.1(C-6′-OCH3),104.7(C-2′-Gal-1″),73.4(C-2″),75.0(C-3″),69.6(C-4″),76.6(C-5″),61.7(C-6″),111.0(C-3′-Ara-1″′),83.5(C-2″′),77.5(C-3″′),85.4(C-4″′),62.3(C-5″′),106.2(C-21-Fuc-1″″),69.4(C-2″″),74.2(C-3″″),69.6(C-4″″),67.8(C-5″″),16.3(C-6″″),167.2(C-3″″-Ang-1),127.7(C-3″″-Ang-2),138.4(C-3″″-Ang-3),15.8(C-3″″-Ang-4),20.6(C-3″″-Ang-5),167.3(C-4″″-Ang-1),127.9(C-4″″-Ang-2),138.8(C-4″″-Ang-3),15.9(C-4″″-Ang-4),20.4(C-4″″-Ang-5),170.6(C-22-OCOCH3),20.6(C-22-OCOCH3),52.1(C-6′-OCH3).
化合物93-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21-O-(3″″,4″″-二-O-当归酰基)-β-D-吡喃呋糖基-22-O-乙酰基-barringtogenolC
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):δ3.23(1H,dd,J=11.7Hz,J=4.3Hz,H-3),5.41(1H,brs,H-12),C-3-GlcUA:4.91(1H,d,J=7.6Hz,H-1′);C-2′-Gal:5.36(1H,d,J=7.8Hz,H-1″);C-3′-Ara:6.06(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.7(C-1),26.6(C-2),89.6(C-3),39.7(C-4),55.8(C-5),18.4(C-6),33.1(C-7),40.0(C-8),46.9(C-9),36.8(C-10),23.8(C-11),123.4(C-12),143.1(C-13),41.6(C-14),34.8(C-15),68.7(C-16),47.8(C-17),40.0(C-18),47.8(C-19),37.8(C-20),85.7(C-21),73.9(C-22),27.9(C-23),16.6(C-24),15.6(C-25),16.9(C-26),27.5(C-27),63.9(C-28),30.2(C-29),20.1(C-30),105.2(C-3-GlcUA-1′),76.5(C-2′),86.1(C-3′),71.4(C-4′),78.7(C-5′),169.6(C-6′),104.8(C-2′-Gal-1″),73.5(C-2″),75.1(C-3″),69.7(C-4″),76.7(C-5″),61.8(C-6″),111.1(C-3′-Ara-1″′),83.6(C-2″′),77.6(C-3″′),85.4(C-4″′),62.2(C-5″′),105.4(C-21-Fuc-1″″),70.2(C-2″″),74.4(C-3″″),71.4(C-4″″),68.9(C-5″″),16.8(C-6″″),167.4(C-3″″-Ang-1),127.9(C-3″″-Ang-2),138.1(C-3″″-Ang-3),15.9(C-3″″-Ang-4),20.6(C-3″″-Ang-5),167.5(C-4″″-Ang-1),128.2(C-4″″-Ang-2),139.0(C-4″″-Ang-3),16.1(C-4″″-Ang-4),20.8(C-4″″-Ang-5),171.6(C-22-OCOCH3),22.1(C-22-OCOCH3),65.1(C-6′-n-Bu-1),30.8(C-6′-n-Bu-2),19.2(C-6′-n-Bu-3),13.7(C-6′-n-Bu-4).
化合物103-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-16-O-乙酰基-21,22-O-二-当归酰基-barringtogenolC
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):δ3.23(1H,dd,J=11.8,4.4Hz,H-3),5.42(1H,brs,H-12),C-3-GlcUA:4.88(1H,d,J=7.6Hz,H-1′);C-2′-Gal:5.35(1H,d,J=7.8Hz,H-1″);C-3′-Ara:6.06(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.6(C-1),26.5(C-2),89.9(C-3),39.6(C-4),55.6(C-5),18.2(C-6),33.0(C-7),39.9(C-8),46.8(C-9),36.7(C-10),23.7(C-11),125.1(C-12),140.9(C-13),41.1(C-14),30.7(C-15),72.1(C-16),47.1(C-17),39.5(C-18),46.9(C-19),36.1(C-20),78.0(C-21),72.4(C-22),27.8(C-23),16.6(C-24),15.5(C-25),16.7(C-26),26.9(C-27),63.3(C-28),29.5(C-29),19.7(C-30),105.2(C-3-GlcUA-1′),76.3(C-2′),85.9(C-3′),71.4(C-4′),78.6(C-5′),170.0(C-6′),104.8(C-2′-Gal-1″),73.4(C-2″),75.2(C-3″),69.7(C-4″),76.7(C-5″),61.8(C-6″),111.1(C-3′-Ara-1″′),83.6(C-2″′),77.6(C-3″′),85.4(C-4″′),62.2(C-5″′),167.7(C21-Ang-1),128.5(C21-Ang-2),138.5(C21-Ang-3),15.9(C21-Ang-4),21.0(C21-Ang-5),167.2(C22-Ang-1),128.3(C22-Ang-2),138.2(C22-Ang-3),15.7(C22-Ang-4),20.9(C22-Ang-5),52.3(C-6′-OCH3),170.1(C16-OCOCH3),22.0(C16-OCOCH3).
化合物113-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21-O-环氧化当归酰基-22-O-当归酰基-barringtogenolC
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):δ3.23(1H,dd,J=11.8,4.4Hz,H-3),5.49(1H,brs,H-12),C-3-GlcUA:4.92(1H,d,J=7.4Hz,H-1′);C-2′-Gal:5.33(1H,d,J=7.7Hz,H-1″);C-3′-Ara:5.99(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.7(C-1),26.6(C-2),89.9(C-3),39.7(C-4),55.7(C-5),18.4(C-6),33.0(C-7),40.0(C-8),46.9(C-9),36.8(C-10),23.7(C-11),124.4(C-12),142.6(C-13),41.6(C-14),34.8(C-15),68.6(C-16),48.2(C-17),40.0(C-18),47.0(C-19),36.5(C-20),80.6(C-21),73.0(C-22),
27.9(C-23),16.6(C-24),15.6(C-25),16.8(C-26),27.5(C-27),63.3(C-28),29.5(C-29),20.3(C-30),105.2(C-C-3-GlcUA-1′),76.5(C-2′),86.0(C-3′),71.4(C-4′),78.7(C-5′),169.6(C-6′),104.8(C-2′-Gal-1″),73.4(C-2″),75.1(C-3″),69.7(C-4″),76.7(C-5″),61.8(C-6″),111.1(C-3′-Ara-1″′),83.6(C-2″′),77.5(C-3″′),85.4(C-4″′),62.2(C-5″′),169.8(C-21-epoxya-1),60.2(C-21-epoxya-2),59.9(C-21-epoxya-3),13.9(C-21-epoxya-4),19.9(C-21-epoxya-5),167.5(C-22-Ang-1),128.5(C-22-Ang-2),139.4(C-22-Ang-3),16.1(C-22-Ang-4),20.8(C-22-Ang-5),65.1(C-6′-n-Bu-1),30.8(C-6′-n-Bu-2),19.2(C-6′-n-Bu-3),13.7(C-6′-n-Bu-4).
化合物123-O-(3′-O-当归酰基)-β-D-吡喃葡萄糖基-28-O-(2″-O-α-L-吡喃鼠李糖基)-β-D-吡喃葡萄糖基-16-deoxy-barringtogenolC
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):δ3.37(1H,dd,J=11.7,4.4Hz,H-3),5.49(1H,brs,H-12),C-3-Glc:4.97(1H,d,J=7.7Hz,H-1′);C-28-Gal:4.79(1H,d,J=7.9Hz,H-1″);C-2″-Rha:6.68(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ39.5(C-1),25.8(C-2),89.0(C-3),38.7(C-4),55.6(C-5),18.4(C-6),32.8(C-7),40.3(C-8),47.9(C-9),36.8(C-10),24.0(C-11),123.9(C-12),143.2(C-13),41.9(C-14),26.5(C-15),18.4(C-16),43.2(C-17),41.3(C-18),46.4(C-19),36.4(C-20),76.8(C-21),74.8(C-22),28.1(C-23),16.9(C-24),15.7(C-25),16.8(C-26),26.3(C-27),74.9(C-28),30.4(C-29),19.6(C-30),106.7(C-3-glc-1′),73.6(C-2′),79.4(C-3′),69.5(C-4′),76.8(C-5′),62.3(C-6′),168.2(C-3′-Ang-1),129.0(C-3′-Ang-2),136.8(C-3′-Ang-3),15.9(C-3′-Ang-4),20.8(C-3′-Ang-5),103.6(C-28-glc-1″′),80.3(C-2″′),77.9(C-3″′),71.7(C-4″′),78.1(C-5″′),62.6(C-6″′),100.5(C-2″′-Rha-1″″),72.6(C-2″″),72.3(C-3″″),74.3(C-4″″),69.1(C-5″″),18.9(C-6″″).
化合物133-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21-O-(3″″,4″″-二-O-当归酰基)-α-L-吡喃鼠李糖基-22-O-乙酰基-barringtogenolC
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):5.47(1H,brs,H-12),C-3-GlUA:4.88(1H,d,J=7.3Hz,H-1′);C-2′-Gal:5.34(1H,d,J=7.5Hz,H-1″);C-3′-Ara:6.03(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.8(C-1),26.6(C-2),89.9(C-3),39.7(C-4),55.7(C-5),18.4(C-6),33.0(C-7),40.0(C-8),46.9(C-9),36.7(C-10),23.9(C-11),124.1(C-12),142.9(C-13),41.8(C-14),34.8(C-15),70.0(C-16),46.6(C-17),40.4(C-18),47.6(C-19),37.1(C-20),92.1(C-21),76.7(C-22),27.8(C-23),16.6(C-24),15.6(C-25),16.9(C-26),27.5(C-27),62.2(C-28),29.8(C-29),20.2(C-30),105.2(C-3-GlcUA-1′),76.5(C-2′),86.0(C-3′),71.3(C-4′),78.7(C-5′),169.6(C-6′),104.8(C-2′-Gal-1″),73.5(C-2″),75.1(C-3″),69.7(C-4″),76.7(C-5″),61.7(C-6″),111.1(C-3′-Ara-1″′),83.6(C-2″′),77.5(C-3″′),85.4(C-4″′),62.3(C-5″′),106.2(C-21-Rha-1″″),71.2(C-2″″),74.3(C-3″″),70.9(C-4″″),69.7(C-5″″),19.3(C-6″″),167.3(C-3″″-Ang-1),128.0(C-3″″-Ang-2),138.9(C-3″″-Ang-3),16.0(C-3″″-Ang-4),20.7(C-3″″-Ang-5),167.3(C-4″″-Ang-1),127.8(C-4″″-Ang-2),138.5(C-4″″-Ang-3),15.9(C-4″″-Ang-4),20.2(C-4″″-Ang-5),170.7(C-22-OCOCH3),20.5(C-22-OCOCH3),65.1(C-6′-n-Bu-1),30.8(C-6′-n-Bu-2),19.2(C-6′-n-Bu-3),13.7(C-6′-n-Bu-4).
化合物143-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21,22-二-O-当归酰基-R1-barrigenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):5.54(1H,brs,H-12),C-3-GlUA:4.90(1H,d,J=7.6Hz,H-1′);C-2′-Gal:5.33(1H,d,J=7.7Hz,H-1″);C-3′-Ara:6.01(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.9(C-1),26.6(C-2),89.9(C-3),39.6(C-4),55.6(C-5),18.8(C-6),36.3(C-7),41.0(C-8),47.1(C-9),37.0(C-10),24.0(C-11),125.4(C-12),143.7(C-13),47.7(C-14),67.5(C-15),73.6(C-16),48.4(C-17),41.4(C-18),46.9(C-19),36.7(C-20),78.6(C-21),73.4(C-22),7.8(C-23),16.7(C-24),15.7(C-25),17.5(C-26),21.2(C-27),63.1(C-28),29.5(C-29),20.2(C-30),105.2(C-3-GlcUA-1′),76.5(C-2′),86.1(C-3′),71.4(C-4′),78.7(C-5′),169.6(C-6′),104.8(C-2′-Gal-1″),73.6(C-2″),75.1(C-3″),69.7(C-4″),76.7(C-5″),61.8(C-6″),111.1(C-3′-Ara-1″′),83.6(C-2″′),77.6(C-3″′),85.4(C-4″′),62.3(C-5″′),167.7(C-21-Ang-1),128.9(C-21-Ang-2),136.5(C-21-Ang-3),15.8(C-21-Ang-4),21.0(C-21-Ang-5),168.1(C-22-Ang-1),129.1(C-22-Ang-2),137.4(C-22-Ang-3),15.9(C-22-Ang-4),21.2(C-22-Ang-5),65.1(C-6′-n-Bu-1),30.8(C-6′-n-Bu-2),19.2(C-6′-n-Bu-3),13.7(C-6′-n-Bu-4).
化合物153-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21,22-二-O-当归酰基-barringogenolC
白色粉末(甲醇),10%浓硫酸乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):5.46(1H,brs,H-12),C-3-GlUA:4.92(1H,d,J=7.6Hz,H-1′);C-2′-Gal:5.36(1H,d,J=7.7Hz,H-1″);C-3′-Ara:6.05(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.7(C-1),26.6(C-2),89.9(C-3),39.7(C-4),55.7(C-5),18.4(C-6),33.1(C-7),40.0(C-8),46.9(C-9),36.4(C-10),23.8(C-11),123.9(C-12),142.8(C-13),41.6(C-14),34.8(C-15),70.0(C-16),46.6(C-17),40.4(C-18),47.6(C-19),37.1(C-20),92.1(C-21),76.7(C-22),27.8(C-23),16.6(C-24),15.6(C-25),16.9(C-26),27.5(C-27),62.2(C-28),29.8(C-29),20.2(C-30),105.2(C-3-GlcUA-1′),76.5(C-2′),86.1(C-3′),71.4(C-4′),78.7(C-5′),169.6(C-6′),104.8(C-2′-Gal-1″),73.6(C-2″),75.1(C-3″),69.7(C-4″),76.7(C-5″),61.6(C-6″),111.1(C-3′-Ara-1″′),83.6(C-2″′),77.5(C-3″′),85.4(C-4″′),62.2(C-5″′),167.7(C-21-Ang-1),128.9(C-21-Ang-2),137.0(C-21-Ang-3),15.8(C-21-Ang-4),20.8(C-21-Ang-5),168.1(C-22-Ang-1),129.0(C-22-Ang-2),137.2(C-22-Ang-3),15.9(C-22-Ang-4),21.0(C-22-Ang-5),65.1(C-6′-n-Bu-1),30.8(C-6′-n-Bu-2),19.2(C-6′-n-Bu-3),13.7(C-6′-n-Bu-4).化合物163-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-24-羟基-21,22-二-O-当归酰基-R1-barrigenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):5.54(1H,brs,H-12),C-3-GlUA:4.89(1H,d,J=7.3Hz,H-1′);C-2′-Gal:5.51(1H,d,J=7.5Hz,H-1″);C-3′-Ara:6.06(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.7(C-1),26.6(C-2),91.4(C-3),43.6(C-4),55.9(C-5),18.8(C-6),36.5(C-7),41.0(C-8),47.0(C-9),36.8(C-10),24.2(C-11),125.2(C-12),143.7(C-13),47.7(C-14),67.5(C-15),73.6(C-16),48.3(C-17),41.1(C-18),46.9(C-19),36.3(C-20),78.6(C-21),73.3(C-22),22.2(C-23),63.1(C-24),15.7(C-25),17.4(C-26),21.0(C-27),63.3(C-28),29.5(C-29),20.2(C-30),104.8(C-3-GlcUA-1′),78.6(C-2′),86.5(C-3′),71.4(C-4′),77.4(C-5′),169.3(C-6′),103.9(C-2′-Glc-1″),75.5(C-2″),78.2(C-3″),69.5(C-4″),78.6(C-5″),61.3(C-6″),111.3(C-3′-Ara-1″′),83.6(C-2″′),77.9(C-3″′),85.4(C-4″′),62.2(C-5″′),167.7(C-21-Ang-1),128.9(C-21-Ang-2),136.5(C-21-Ang-3),15.7(C-21-Ang-4),21.0(C-21-Ang-5),168.1(C-22-Ang-1),129.1(C-22-Ang-2),137.4(C-22-Ang-3),15.9(C-22-Ang-4),21.2(C-22-Ang-5),65.1(C-6′-n-Bu-1),30.81(C-6′-n-Bu-2),19.21(C-6′-n-Bu-3),13.71(C-6′-n-Bu-4).
化合物173-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-24-羟基-21,22-二-O-当归酰基-R1-barrigenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):5.54(1H,brs,H-12),C-3-GlUA:4.89(1H,d,J=7.3Hz,H-1′);C-2′-Gal:5.51(1H,d,J=7.5Hz,H-1″);C-3′-Ara:6.06(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.6(C-1),26.6(C-2),91.5(C-3),43.6(C-4),55.9(C-5),18.8(C-6),36.5(C-7),41.0(C-8),46.9(C-9),36.8(C-10),24.2(C-11),125.2(C-12),143.7(C-13),47.7(C-14),67.5(C-15),73.5(C-16),48.3(C-17),41.3(C-18),46.9(C-19),36.3(C-20),78.4(C-21),73.3(C-22),22.2(C-23),63.1(C-24),15.9(C-25),17.3(C-26),21.0(C-27),63.3(C-28),29.5(C-29),20.2(C-30),105.2(C-3-GlcUA-1′),76.5(C-2′),86.0(C-3′),71.3(C-4′),78.7(C-5′),169.6(C-6′),104.8(C-2′-Glc-1″),73.5(C-2″),75.1(C-3″),69.7(C-4″),76.7(C-5″),61.7(C-6″),111.1(C-3′-Ara-1″′),83.6(C-2″′),77.5(C-3″′),85.4(C-4″),′62.3(C-5″′),167.3(C-21-Ang-1),128.0(C-21-Ang-2),138.9(C-21-Ang-3),16.0(C-21-Ang-4),20.7(C-21-Ang-5),167.3(C-22-Ang-1),127.8(C-22-Ang-2),138.5(C-22-Ang-3),15.9(C-22-Ang-4),20.2(C-22-Ang-5),52.3(C-6′-OCH3).
化合物183-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-甲基酯-O-吡喃葡萄糖醛酸基-24-羟基-21,22-二-O-当归酰基-barringogenolC
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):5.54(1H,brs,H-12),C-3-GlUA:4.89(1H,d,J=7.3Hz,H-1′);C-2′-Gal:5.51(1H,d,J=7.5Hz,H-1″);C-3′-Ara:6.06(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.4(C-1),26.5(C-2),91.6(C-3),43.6(C-4),56.0(C-5),18.4(C-6),33.1(C-7),41.6(C-8),46.7(C-9),36.4(C-10),24.0(C-11),125.2(C-12),142.7(C-13),41.6(C-14),34.8(C-15),68.6(C-16),48.0(C-17),40.0(C-18),47.2(C-19),36.3(C-20),78.7(C-21),73.5(C-22),27.5(C-23),63.2(C-24),15.5(C-25),16.6(C-26),27.5(C-27),63.5(C-28),29.5(C-29),20.3(C-30),104.8(C-3-GlcUA-1′),78.7(C-2′),86.3(C-3′),71.5(C-4′),77.5(C-5′),169.8(C-6′),103.9(C-2′-Glc-1″),75.5(C-2″),78.2(C-3″),69.5(C-4″),78.7(C-5″),61.3(C-6″),111.2(C-3′-Ara-1″′),83.6(C-2″′),77.8(C-3″′),85.4(C-4″′),62.3(C-5″′),167.7(C-21-Ang-1),128.9(C-2),137.1(C-3),15.8(C-4),20.8(C-5),168.1(C-22-Ang-1),129.0(C-2),137.2(C-3),15.9(C-4),21.0(C-5),52.3(C-6′-OCH3).
化合物193-O-(3′-O-α-L-呋喃阿拉伯糖基-2′-O-β-D-吡喃半乳糖基)-β-D-6′-丁基酯-O-吡喃葡萄糖醛酸基-21-O-当归酰基-22-O-(2-甲基)-丁酰基-R1-barrigenol
白色粉末(甲醇),10%浓硫酸/乙醇溶液显紫色。1HNMR(600MHz,pridine-d5):5.54(1H,brs,H-12),C-3-GlUA:4.91(1H,d,J=7.3Hz,H-1′);C-2′-Gal:5.53(1H,d,J=7.5Hz,H-1″);C-3′-Ara:6.03(1H,brs,H-1″′).13CNMR(150MHz,pridine-d5):δ38.9(C-1),26.5(C-2),89.9(C-3),39.6(C-4),55.5(C-5),18.8(C-6),36.4(C-7),40.9(C-8),47.1(C-9),36.9(C-10),24.0(C-11),125.2(C-12),143.7(C-13),47.7(C-14),67.5(C-15),72.9(C-16),48.5(C-17),41.4(C-18),46.8(C-19),36.7(C-20),78.4(C-21),73.1(C-22),27.8(C-23),16.7(C-24),15.7(C-25),17.5(C-26),21.1(C-27),63.1(C-28),29.5(C-29),20.2(C-30),105.2(C-3-GlcUA-1′),76.4(C-2′),86.0(C-3′),71.3(C-4′),78.7(C-5′),169.6(C-6′),104.8(C-2′-Gal-1″),73.4(C-2″),75.1(C-3″),69.7(C-4″),76.7(C-5″),61.8(C-6″),111.1(C-3′-Ara-1″′),83.6(C-2″′),77.5(C-3″′),85.4(C-4″′),62.2(C-5″′),167.5(C-21-Ang-1),128.6(C-21-Ang-2),138.7(C-21-Ang-3),15.8(C-21-Ang-4),21.1(C-21-Ang-5),176.4(C-22-MB-1),41.0(C-22-MB-2),29.6(C-22-MB-3),11.84(C-22-MB-4),17.0(C-22-MB-5),65.1(C-6′-n-Bu-1),30.8(C-6′-n-Bu-2),19.2(C-6′-n-Bu-3),13.7(C-6′-n-Bu-4).
实施例4:19个三萜皂苷类化合物及两种文冠果提取物的体外抗人脑胶质瘤(U87-MG)、人肝癌细胞(HepG-2)、人胰腺癌细胞(PANC-1)、人胃癌细胞(NCI-N87)、人结肠癌细胞(Colo-320DM)的活性测定
通过CCK-8检测试剂盒检测化合物1-19和2种提取物对5种人源肿瘤细胞株(Colo-320DM,HepG-2、U87-MG、PANC-1、NCI-N87)的增殖抑制作用IC50。实验操作
(1)细胞培养
收集对数生长期细胞,计数,用完全培养基重新悬浮细胞,然后调整细胞浓度至合适浓度,接种96孔板,每孔接种100μl细胞悬液,最后细胞在37℃,100%相对湿度,5%CO2培养箱中孵育24小时。
(2)样品制备
用DMSO稀释化合物至相应浓度。
(3)IC50实验
(a)接种细胞于96孔板,每孔加100μl细胞悬液,于37℃,100%相对湿度,5%CO2培养箱中孵育24小时。
(b)加入用DMSO稀释的待测化合物,设置10个浓度点。
(c)加药后的细胞置于37℃,100%相对湿度,5%CO2培养箱中孵育72小时;
(d)吸弃培养基,加入含10%CCK-8的完全培养基置于37℃培养箱中孵育2~6小时,染色。
(e)酶标仪上测定450nm波长处的吸光度,以650nm处吸光度作为参比,计算抑制率。
(5)数据处理
按下式计算药物对肿瘤细胞生长的抑制率:
肿瘤细胞生长抑制率%=[(Ac-As)/(Ac-Ab)]×100%
As:样品的OA(细胞+CCK-8+待测化合物)
Ac:阴性对照的OA(细胞+CCK-8+DMSO)
Ab:阳性对照的OA(培养基+CCK-8+DMSO)
采用软件GraphpadPrism5拟合IC50曲线并计算出IC50值。
19个化合物及两种文冠果提取物的IC50值见下表
文冠果提取物的IC50值见下表
Claims (10)
1.三萜皂苷类化合物,其特征在于,其化学结构如下:
其中,R1可以为当归酰基、环氧当归酰基或者双当归酰基取代的呋糖基;R2可以为当归酰基、乙酰基或者2-甲基丁酰基;R3为三糖基或者双糖基取代;R4为羟基或者乙酰基;R5为羟基或者氢;R6为甲基或者羟甲基;R7为单糖基、双糖基、三糖基、当归酰基取代的糖基、正丁酯基取代的糖基、甲酯基取代的糖基。
2.权利要求1所述化合物,其特征在于,选自:
3.一种药物组合物,包含权利要求1或2所述的三萜皂苷类化合物和药学上可接受的载体。
4.文冠果果壳提取物,其特征在于,采用以下方法提取:
取干燥文冠果果壳、果柄粉碎,然后按照重量体积比1:2-1:8加入50%-70%乙醇,回流提取1-3次,每次0.5-4h,所得提取液经减压回收溶剂浓缩,浓缩液依次用1-5倍体积的乙酸乙酯、正丁醇萃取等体积的乙酸乙酯和正丁醇萃取1-5次,得文冠果正丁醇萃取物,即得提取物1。
5.文冠果果壳提取物,其特征在于,采用以下方法提取:
取干燥文冠果果壳,粉碎,然后按照重量体积比1:2-1:8加入50%-70%乙醇,回流提取1-3次,每次0.5-4h,所得提取液经减压回收溶剂浓缩,浓缩液经大孔树脂AB-8分离纯化,以乙醇-水为溶剂进行梯度洗脱,收集30%-80%乙醇提取物,即得提取物2。
6.如权利要求1或2所述的三萜皂苷类化合物的制备方法,其特征在于,
取干燥文冠果果壳、果柄粉碎,然后按照重量体积比1:2-1:8加入50%-70%乙醇,回流提取1-3次,每次0.5-4h,所得提取液经减压回收溶剂浓缩,浓缩液依次用1-5倍体积的乙酸乙酯、正丁醇萃取等体积的乙酸乙酯和正丁醇萃取1-5次,得文冠果正丁醇萃取物,即得提取物1。
或取干燥文冠果果壳,粉碎,然后按照重量体积比1:2-1:8加入50%-70%乙醇,回流提取1-3次,每次0.5-4h,所得提取液经减压回收溶剂浓缩,浓缩液经大孔树脂AB-8分离纯化,以乙醇-水(0%,10%,30%,50%,80%,95%)为溶剂进行梯度洗脱,收集30%-80%乙醇提取物,即得提取物2;
应用硅胶柱色谱对提取物1或2进行分离,用二氯甲烷:甲醇:水30:1:1~1:1:1进行梯度洗脱,所得流份可经薄层检识后合并,所得流份应用中低压或HPLC色谱制备分离,以甲醇:水(10:90~100:0)或乙腈:水(10:90~100:0)进行梯度洗脱制备的化合物,或流份以反复硅胶柱色谱法,以氯仿-甲醇或二氯甲烷-甲醇(100:0~0:100)为流动相梯度洗脱,所得流份经薄层检识后合并,流份再用SephadexLH-20脱色素,以甲醇/水为流动相,分离制备得到化合物。
所述有机溶剂为甲醇、乙醇、丙酮、正丁醇、乙酸乙酯、石油醚、氯仿、二氯甲烷中的一种或几种。所述提取温度在于30-100℃,提取时间0.5-4h;所述分离方法为综合色谱分离法。
7.具有如下结构的三萜皂苷类化合物的制备方法,其特征在于,取干燥文冠果果壳、果柄粉碎,然后按照重量体积比1:2-1:8加入50%-70%乙醇,回流提取1-3次,每次0.5-4h,所得提取液经减压回收溶剂浓缩,浓缩液依次用1-5倍体积的乙酸乙酯、正丁醇萃取等体积的乙酸乙酯和正丁醇萃取1-5次,得文冠果正丁醇萃取物,即得提取物1。
或取干燥文冠果果壳,粉碎,然后按照重量体积比1:2-1:8加入50%-70%乙醇,回流提取1-3次,每次0.5-4h,所得提取液经减压回收溶剂浓缩,浓缩液经大孔树脂AB-8分离纯化,以乙醇-水(0%,10%,30%,50%,80%,95%)为溶剂进行梯度洗脱,,收集30%-80%乙醇提取物,即得提取物2;
应用硅胶柱色谱对提取物1或2进行分离,用二氯甲烷:甲醇:水30:1:1~1:1:1进行梯度洗脱,所得流份可经薄层检识后合并,所得流份应用中低压或HPLC色谱制备分离,以甲醇:水(10:90~100:0)或乙腈:水(10:90~100:0)进行梯度洗脱制备的化合物,或流份以反复硅胶柱色谱法,以氯仿-甲醇或二氯甲烷-甲醇(100:0~0:100)为流动相梯度洗脱,所得流份经薄层检识后合并,流份再用SephadexLH-20脱色素,以甲醇/水为流动相,分离制备得到化合物。
所述有机溶剂为甲醇、乙醇、丙酮、正丁醇、乙酸乙酯、石油醚、氯仿、二氯甲烷中的一种或几种。所述提取温度在于30-100℃,提取时间0.5-4h;所述分离方法为综合色谱分离法;
8.一种药物制剂,其特征在于,以权利要求1或2所述的化合物或权利要求3所述的组合物或权利要求4或5所述的文冠果果壳提取物作为活性成分。
9.权利要求1或2所述的化合物或权利要求3所述的组合物或权利要求4或5所述的提取物在在制备抗肿瘤药物中的应用。
10.如权利要求9所述的应用,其特征在于,所述肿瘤为脑胶质瘤、肝癌、胰腺癌、胃癌或结肠癌。
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CN109142610A (zh) * | 2018-11-13 | 2019-01-04 | 吕梁学院 | 一种文冠果中三萜类化合物的提取检验与含量测定的方法 |
CN113072608A (zh) * | 2020-01-03 | 2021-07-06 | 沈阳药科大学 | 三萜皂苷类化合物及其用途 |
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