CN1680424A - 一种活性皂苷的制备方法和用途 - Google Patents
一种活性皂苷的制备方法和用途 Download PDFInfo
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Abstract
本发明公开了具有潜在药用价值的如通式I所示皂苷的合成方法,及其在抗炎、抗癌药物和组合物中的应用。通式I中,R为H,Me,SO3 -或其它糖单元,R1可为H,CH3,CH2OH,CH2OSO3 -,COOH或其它糖单元,R2,R3可为H,OH,OSO3 -,或其它糖单元。
Description
发明领域
本发明涉及生物活性皂苷的合成和应用领域。
发明背景
天然寡糖皂苷作为糖辍合物在生理学和药理学具有很好的生物活性(Hostettmann,K.;Marston,A.Saponins;Cambridge University Press,1995)。例如,Dioscin,Polyphyllin D,Balanitin 7等皂苷就具有抗癌、杀菌的活性((a)Nakano,K.;Murakami,K.;Takaishi,Y.;Tomimatsu,T.;Nohara,T.Chem.Pharm.Bull.1989,37,116;(b)Hufford,C.D.;Liu,S.;Clark,A.M.J.Nat.Prod.1988,51,94-98;(c)Liu,C.;Chen,Y.Acta Pharm.Sinica 1984,19,799;(d)Namba,T.;Huang,X.;Shu,Y.;Huang,S.;Hattoti,M.;Kakiuchi,N.;Wang,Q.;Xu,G.Plant Medica 1989,55,501-506;(e)Zhou,J.PureAppl.Chem.1989,61,457-460);从葱科植物(Allium nutans)的根茎分离提取出的皂苷具有抗肿瘤和降低血清中胆固醇的作用(Akhov,L.S.;Musienko,M.M.;Piacente,S.;Pizza,C.;Oleszek,W.J.Agric.Food Chem.1999,47,3193-3196);从茄科植物(Solanumindicum)分离提取的皂苷具有抗菌消炎的作用(Yahara,S.;Nakamura,T.;Somera,Y.;Matsumoto,T.;Yamashita,T.;Nohara,T.Phytochemistry,1996,43,1319-1323);研究表明Solamargine结构中的鼠李糖基结构在引发细胞死亡过程中起着至关重要的作用(Chang,L.-C.;Tsai,T-R.;Wang,J.-J.;Lin,C.-N.;Kuo,K.-W.Biochem.Biophys.Res.Commun.1998,242,21-25)。上述的这些具有生物活性的皂苷以及一些N-连接的寡糖和植物多糖的部分片段都含有2-;2,3-或2,4-支化的寡糖结构部分。
围绕如何简便高效地合成寡糖和糖辍合物已开展了大量的工作,而且也发展了许多新颖的、有效的糖基化反应和合成策略((a)Toshima,K.;Tasuta,K.Chem.Rev.1993,93,1503-1531;(b)Schmidt,R.R.;Kinzy,W.Adv.Carbohydr Chem.Biochem.1994,50,21;(c)Garegg,P.J.Adv.Carbohydr.Chem.Biochem.1997,52,179)。对含有糖基结构的天然皂苷来说,传统合成方法有三种。其一,先将还原端糖基接在皂苷元上,然后对糖基部分进行保护-去保护修饰,再进行不同位置的糖基化反应,得到2-,2,3-或2,4-支化的天然皂苷。其二,先对还原端糖基进行适当修饰,用具有邻基参与的酰基保护基修饰糖基C-2位的羟基以保证接皂苷元时β-糖苷键的形成。然而,实验中也发现脱除C-2位的酰基很困难(Deng,S.;Yu,B.;Hui,Y.;Yu,B.;Han,X.Carbohydr.Res.1999,317,53-62)。而上述两种方法的缺点是路线冗长而且合成效率低。其三,先合成糖基部分,再与相应的皂苷元进行糖苷化反应,此方法由于还原端的糖基部分的C-2位上没有邻基参与效应而容易得到α、β混合物,给分离提纯带来了困难(Ikeda,T.;Miyashita,H.;Kajimoto,T.;Nohara,T.Tetrahedron Lett.2001,42,2353-2356)。考虑到上述方法的缺陷,我们发明了以下合成皂苷的简易方法,其核心是用部分保护的硫代糖苷做供体来简便合成上述含有2-;2,3-或2,4-支化的天然皂苷。
本发明通过制备相关寡糖皂苷,有助于开发抗肿瘤或抗炎症的药物,也可用于开发具有调节免疫和防癌功能的食品添加剂。
实施实例:
一般方法:旋光度在25℃时用Perkin-Elmer 241 MC自动旋光仪侧得。1H NMR由Bruker ARX 400在CDCl3中测得,以四甲基硅为内标。质谱用VG PLATFORM质谱仪,用ESI技术进样。薄层色谱(TLC)由HF254硅胶板上用30%(v/v)的硫酸甲醇溶液或紫外(UV)检测器检测。柱色谱采用100-200目的硅胶,用乙酸乙酯-石油醚(60-90℃)作为淋洗液,溶液在小于60℃时减压蒸馏,以下未特别说明的化合物都是可商购或可参照文献制备的物质。
一、薯蓣苷元β-D-木吡喃糖基-(1→3)-[α-L-鼠李吡喃糖基-(1→2)]-β-D-半乳吡喃糖的制备10
流程1是天然皂苷10的合成路线图。部分保护的半乳吡喃糖异丙硫苷3是从半乳吡喃糖异丙硫苷1经4,6位的选择性苄叉基保护(→2)及2,3位的选择性9-芴甲氧基羰基(Fmoc)保护得到。在-42℃,硫代糖苷3和薯蓣皂苷元用氮-碘代琥珀酰亚胺(NIS)和三甲基硅基三氟甲磺酸酯(TMSOTf)催化进行缩合反应得约75%的4。在0℃,等当量的化合物4和5用TMSOTf催化反应得到二糖皂苷6。不分离往反应体系加入20当量三乙胺可脱除C-3位的9-芴甲氧基羰基保护基,一釜反应得到二糖皂苷受体7,两步产率85%。用苯甲酰化木吡喃亚胺酯8做糖基化供体和受体7进行偶联得到77%的三糖皂苷9,其木吡喃糖的构象发生翻转(4C1→4C1)。1H NMR谱图上H-1的化学位移出峰在5.24ppm(J1,21.1Hz)处,H-3的化学位移出峰在5.64ppm(J2,3=J3,4=3.2Hz)处;13C NMR谱图上C-1的化学位移出峰在100.03ppm处,说明木糖与半乳糖间为β(1→3)连接,但木糖的构象为4C1而非4C1。在70℃下,化合物9用80%的醋酸水溶液脱除4,6位的苄叉基;然后在无水甲醇中,用1N的氢氧化钠水溶液(调pH约9-10)脱除糖基上的酰基保护基,得到天然皂苷10。其木吡喃糖环的构象由4C1变为4C1,可从其1H NMR谱图上化学位移5.05ppm处的H-1双峰间的偶合常数(J1,27.5Hz)看出。从起始原料出发,天然皂苷10合成流程仅仅需要六步,总产率为34%。
流程1:薯蓣苷元β-D-木吡喃糖基-(1→3)-[α-L-鼠李吡喃糖基-(1→2)]-β-D-半乳吡喃糖的制备
(1)异丙硫基4,6-二-氧-苄叉基-β-D-半乳吡喃糖苷2的制备
将β-D-半乳吡喃异丙硫苷(2.38克,10毫摩尔)溶在10毫升DMF中,加入PhCH(OMe)2(1.82克,12毫摩尔)和催化量的对甲苯磺酸(100毫克)。在65-75℃下,减压搅拌1.5-2小时,反应完毕。用饱和碳酸氢钠水溶液中和至中性,乙酸乙酯(2×50毫升)萃取,将有机相收集,用无水硫酸钠干燥,减压浓缩,剩余物用硅胶柱色谱分离纯化,以乙酸乙酯淋洗,得白色固体2(2.67克,82%):旋光值:[α]D 20-62°(c1,CHCl3);核磁1H NMR(CDCl3):δ1.34,1.38(2d,2×3H,J 6.9Hz,(CH3)2CH),3.24-3.32(m,1H,(CH3)2CH),3.53(br d,1H,J 1.2Hz,H-5),3.68(dd,1H,J 9.3,3.6Hz,H-3),3.77(t,1H,J 9.3Hz,H-2),4.02(brd,1H,J 12.5Hz,H-6a),4.24(br s,1H,H-4),4.33(br d,1H,J 12.5Hz,H-6b),4.40(d,1H,J 9.3Hz,H-1),5.53(s,1H,PhCH),7.35-7.51(m,5H,Ph)。
(2)异丙硫基3-氧-(9-芴甲氧基羰基)-4,6-二-氧-苄叉基-β-D-半乳吡喃糖苷3的制备
在0℃下,将化合物2(1.0克,3.07毫摩尔)溶在5毫升吡啶中,加入9-芴甲氧基羰基氯(872毫克,3.37毫摩尔)和催化量的DMAP(50毫克)。然后升温至室温,搅拌12小时,反应完毕。减压蒸除溶剂,剩余物用硅胶柱色谱分离纯化,以3∶1石油醚-乙酸乙酯淋洗得泡沫状3(1.48克,88%):旋光值:[α]D 20+31°(c1.8,CHCl3);核磁1H NMR(CDCl3):δ1.36,1.39(2d,2×3H,J 6.9Hz,(CH3)2CH),3.45-3.35(m,1H,(CH3)2CH),3.53(br d,1H,J 1.0Hz,H-5),4.02(dd,1H,J 12.5,1.7Hz,H-6a),4.12(t,1H,J1,2=J2,3=9.6Hz,H-2),4.29(br t,1H,J 7.6Hz,CH of Fmoc),4.34(dd,1H,J 12.5,1.5Hz,H-6b),4.43-4.46(m,3H,H-4,CH2 of Fmoc),4.49(d,1H,J 9.6Hz,H-1),4.77(dd,1H,J 9.6,3.5Hz,H-3),5.50(s,1H,PhCH),7.21-7.76(m,13H,Ph)。
(3)薯蓣苷元3-氧-(9-芴甲氧基羰基)-4,6-二-氧-苄叉基-β-D-半乳吡喃糖苷4
在-40℃,氮气保护下,将硫代糖苷3(0.2毫摩尔)和薯蓣苷元(0.2毫摩尔)溶在干燥的1毫升二氯甲烷中,分别加入0.2毫摩尔NIS和催化量的TMSOTf。搅拌30分钟,TLC检测反应完毕。三乙胺中和,减压浓缩,硅胶柱色谱分离纯化浓缩物,用石油醚-乙酸乙酯(6/1~3/1)淋洗,得纯化产物4。旋光值:[α]D 25-34°(c1.3,CHCl3);核磁1H NMR(CDCl3):δ0.788(s,3H,CH3),0.789(d,3H,J 6.2Hz,CH3),0.89-0.96(m,2H),0.97(d,3H,J 6.9Hz,CH3)),1.03(s,3H,CH3),1.04-2.38(m,22H),3.37(t,1H,J10.9Hz,H-26a),3.46-3.50(m,H-26b,H-5),3.55-3.66(m,1H,H-3α),4.04-4.09(m,2H,H-2,H-6a),4.27-4.34(m,2H,H-6b,CH of Fmoc,4.35-4.50(m,5H,H-16 of diosgenyl,H-1,H-4,CH2 of Fmoc),4.75(dd,1H,J 10.2,3.7Hz,H-3),5.34(m,H-6 of diosgenyl),5.51(s,1H,PhCH2),7.42-8.11(10H,Ph)。
(4)薯蓣苷元2,3,4-三-氧-乙酰基-α-L-鼠李吡喃糖基-(1→2)-4,6-二-氧-苄叉基-β-D-半乳吡喃糖苷7的制备
在0℃,氮气保护下,将化合物4(443毫克,0.50毫摩尔)和乙酰化鼠李糖亚胺酯5(222毫克,0.51毫摩尔)溶于5毫升干燥的二氯甲烷,加入9微升TMSOTf。搅拌1小时后,往反应体系加入过量的三乙胺(20当量),室温下继续搅拌2小时,减压浓缩,用硅胶柱色谱分离纯化浓缩物,以3∶1的石油醚-乙酸乙酯淋洗,得到泡沫状7(397毫克,两步产率84.8%)。7的物理数据:旋光值:[α]D 25-95°(c0.75,CHCl3);核磁1H NMR(CDCl3):δ0.786(s,3H,CH3),0.792(d,3H,J 5.0Hz,CH3),0.97(d,3H,J 6.9Hz,CH3),1.07(s,3H,CH3),1.21(d,3H,J 6.2Hz,H-6′),1.98,2.00,2.12(3s,3×3H,3CH3CO),3.37(t,1H,J 10.9Hz,H-26a of diosgenyl),3.45-3.50(m,H-5,H-26b ofdiosgenyl),3.58-3.67(n,1H,H-3α diosgenyl),3.75-3.85(m,2H,H-2 and H-3),4.07(brd,1H,J 12.3Hz,H-6a),4.16(d,1H,J 2.4Hz,H-4),4.31(br d,1H,H-6b),4.41(q,1H,J 7.5Hz,H-16 of diosgenyl),4.47-4.54(m,2H,H-1,H-5′),5.07(t,1H,J 10.0Hz,H-4′),5.28(dd,1H,J 10.0,3.4Hz,H-3′),5.32(d,1H,J 1.6Hz,H-1′),5.36(dd,1H,J 3.4,1.6Hz,H-2′),5.39(br d,1H,J 5.0Hz,H-6 of diosgenyl),5.54(s,1H,PhCH),7.36-7.51(m,5H,Ph).元素分析Anal.Calcd for C52H72O15:C,66.65;H,7.74.Found:C,66.83;H,7.66。
(5)薯蓣苷元2,3,4-三-氧-苯甲酰基-β-D-木吡喃糖基-(1→3)-[2,3,4-三-氧-乙酰基-α-L-鼠李吡喃糖基-(1→2)]-4,6-二-氧-苄叉基-β-D-半乳吡喃糖苷8
在0℃,氮气保护下,将化合物7(210毫克,0.22毫摩尔)和苯甲酰化木糖亚胺酯8(264毫克,0.25毫摩尔)溶在4毫升干燥的二氯甲烷,加入5微升TMSOTGf。搅拌2小时后,用三乙胺中和,减压蒸除溶剂,用硅胶柱色谱分离纯化浓缩物,以3∶1的石油醚-乙酸乙酯淋洗得到泡沫状9(238毫克,76.9%):旋光值:[α]D 25-102°(c0.5,CHCl3);核磁1H NMR(CDCl3):δ0.774(s,3H,CH3),0.780(d,3H,J 4.9Hz,CH3),0.96(d,3H,J 6.9Hz,CH3),1.02(s,3H,CH3),1.10(d,3H,J 6.1Hz,H-6II),1.87,1.94,2.03(3s,3×3H,3CH3CO),3.36(t,1H,J 10.9Hz,H-26a),3.40-3.48(m,2H,H-5I,H-26b),3.54-3.62(m,1H,H-3α),3.85(br d,1H,J 12.9Hz,H-5aIII),3.91(dd,1H,J 9.6,3.5Hz,H-3I),4.06-4.4.14(m,2H,H-2I,H-6aI),4.31(br d,1H,J 11.9Hz,H-6bI),4.40(q,1H,J 8.0Hz,H-16),4.46(d,1H,J 3.5Hz,H-4I),4.47-4.53(m,1H,H-5II),4.57(d,1H,J 7.7Hz,H-1I),4.69(dd,J 12.9,2.1Hz,H-5bIII),4.97(t,1H,J3,4=J4,5 9.9Hz,H-4II),5.07(br d,1H,J 3.0Hz,H-2III),5.20(s,1H,J 1.1Hz,H-1II),5.24-5.30(m,3H,H-3II,H-1III,H-4III),5.29(dd,1H,J 3.3,1.1Hz,H-2II),5.38(brd,1H,J 5.1Hz,H-6),5.53(s,1H,PhCH),5.64(br t,1H,J3,4=J2,3 3.2Hz,H-3III),7.08-8.06(m,20H,Ph);13C NMR(CDCl3):δ14.47,16.23,17.08,17.12,19.26,20.53,20.76,20.80(2C),28.75,29.38,30.24,31.35,31.38,31.80,32.06,36.90,37.19,38.23,39.71,40.22,41.57,50.06,56.45,58.79,62.07,65.94,66.19,66.32,66.79,67.01,68.28,68.95,69.21,69.94,71.46,71.76,75.94,77.93,80.75,83.54,97.08(C-1II),98.97(C-1I),100.03(C-1III),100.75(PhCH),109.22(C-22),121.77(C-6),140.36(C-5),164.55,165.05,165.46(3C,PhCO),169.94,169.97(3 C,CH3CO,some overlapped).元素分析Anal.Calcd for C78H92O22:C,67.81;H,6.71.Found:C,67.97;H,6.82。
(6)薯蓣苷元β-D-木吡喃糖基-(1→3)-[α-L-鼠李吡喃糖基-(1→2)]-β-D-半乳吡喃糖10
化合物9(183毫克,0.13毫摩尔)溶于15毫升80%醋酸水溶液中,加热至70℃反应。搅拌2小时后,减压蒸除溶剂,所的剩余物溶在6毫升甲醇/二氯甲烷(2∶1)混合溶剂,加入1 N氢氧化钠水溶液至pH值约9-10。室温搅拌6小时,用酸性树脂IR-120(H+)中和。抽滤,滤液浓缩,用硅胶柱色谱分离纯化浓缩物,以3∶1二氯甲烷-甲醇淋洗,得到白色固体10(113毫克,96%):核磁1H NMR(d5-pyridine):δ0.69(d,3H,J 5.3Hz,CH3),0.87(s,3H,CH3),1.05(s,3H,CH3),1.13(d,3H,J 6.9Hz,CH3),1.69(d,3H,J 6.1Hz,H-6II),3.49-3.68(m,3H),3.91(t,1H),3.98-4.04(m,1H),4.06-4.15(m,3H),4.20-4.32(m,3H),4.38-4.43(m,2H),4.53(q,1H,H-5II),4.60(dd,1H),4.73(t,1H),4.80(d,1H),4.90(d,1H),4.93(dd,1H),4.99(d,1H,J 7.7Hz,H-1I),5.05(d,1H,J 7.5Hz,H-1III),5.31(d,1H,J 4.7Hz,H-6),6.29(s,1H,H-1II).质谱ESI(-)-MS found for C44H70O16:877.2(M+Na)+。
二、薯蓣苷元β-D-葡萄吡喃糖基-(1→3)-[α-L-鼠李吡喃糖基-(1→2)]-β-D-半乳吡喃糖的制备10
流程2是天然皂苷15的合成路线图。在0℃,化合物7和1当量11用TMSOTf催化进行区域选择性缩合得β(1→3)连接为主的二糖12(88%)。此部分保护的二糖12和薯蓣苷元在NIS/TMSOTf催化下偶联,得到约63.4%的二糖皂苷13。其1HNMR谱图上,H-1的化学位移出峰在4.33 ppm处,偶合常数为7.5赫兹,说明β糖苷键的形成。化合物13和1.5当量5进行缩合反应,得到84%产率的三糖皂苷14。在70℃下,化合物14用80%的醋酸水溶液脱除苄叉基;然后,溶在甲醇中用1N的氢氧化钠水溶液(调pH约9-10)来脱除糖基上的酰基保护基,得到天然皂苷15。由此,我们从起始原料出发,经五步反应得到天然皂苷15(总产率36%)。
流程2:薯蓣苷元β-D-葡萄吡喃糖基-(1→3)-[α-L-鼠李吡喃糖基-(1→2)]-β-D-半乳吡喃糖的制备
(1)异丙硫基2,3,4,6-四-氧-苯甲酰基-β-D-葡萄吡喃糖基-(1→3)-4,6-二-氧-苄叉基-β-D-半乳吡喃糖苷12
在0℃,氮气保护下,将化合物7(443毫克,0.50毫摩尔)和苯甲酰化葡萄糖亚胺酯11(222毫克,0.51毫摩尔)溶在10毫升干燥的二氯甲烷,加入9微升TMSOTf。搅拌1小时后,用三乙胺中和,减压蒸除溶剂,用硅胶柱色谱分离纯化浓缩物,以4:1的石油醚-乙酸乙酯淋洗得到泡沫状12(511毫克,88.3%):旋光值:[α]D 25-87°(c0.25,CHCl3);核磁1H NMR(CDCl3):δ1.25,1.31(2d,2×3H,J 6.9Hz,(CH3)2CH),3.14-3.21(m,1H,(CH3)2CH),3.27(br s,1H,H-5),3.75(dd,1H,J 9.4,3.2Hz,H-3),3.83(br d,1H,J 11.8Hz,H-6a),3.90(t,1H,J1,2=J2,3 9.4Hz,H-2),4.16-4.24(m,2H,H-6b,H-5′),4.25(d,1H,J 3.2Hz,H-4),4.33(d,1H,J 9.4Hz,H-1),4.54(dd,1H,J 12.2,5.7Hz,H-6a′),4.68(dd,J 12.2,2.8Hz,H-6b′),5.39(s,1H,PhCH),5.40(d,1H,J 7.8Hz,H-1′),5.58(t,1H,J 9.6,7.8Hz,H-2′),5.68(t,1H,J3′,4′=J4′,5′9.6Hz,H-4′),5.92(t,1H,J3′,4′=J2′,3′9.6Hz,H-3′),7.25-7.94(m,25H,Ph).元素分析Anal.Calcd for C50H48O14S:C,66.36;H,5.35.Found:C,66.57;H,5.28。
(2)薯蓣苷元2,3,4,6-四-氧-苯甲酰基-β-D-葡萄吡喃糖基-(1→3)-4,6-二-氧-苄叉基-β-D-半乳吡喃糖苷13
在-42℃,氮气保护下,将化合物12(452毫克,0.50毫摩尔)和薯蓣皂苷元(207毫克,0.50毫摩尔)溶在干燥的10毫升二氯甲烷中,分别加入124毫克(0.55毫摩尔)NIS和11微升TMSOTf。搅拌45分钟后,用三乙胺中和,减压浓缩,硅胶柱色谱分离纯化浓缩物,用3∶1石油醚-乙酸乙酯淋洗,得白色固体13(394毫克,63.4%):旋光值:[α]D 25-24°(c1,CHCl3);核磁1H NMR(CDCl3):δ0.780(s,3H,CH3),0.788(d,3 H,J 6.3Hz,CH3),0.97(d,3H,J 6.9Hz,CH3),1.00(s,3H,CH3),3.23(br s,1H,H-5),3.37(t,1H,J 10.9Hz,H-26a of diosgenyl),3.45-3.57(m,H-3α and H-26b of diosgenyl),3.74(dd,1H,J 9.8,3.3Hz,H-3),3.81-3.88(m,2H,H-2,H-6a),4.15-4.22(m,3H,H-4,H-5′,H-6b),4.33(d,1H,J 7.5Hz,H-1),4.39(q,1H,J 7.5Hz,H-16 of diosgenyl),4.53(dd,1H,J 12.2,5.3Hz,H-6a′),4.68(dd,J 12.2,3.0Hz,H-6b′),5.32(br d,1H,J 5.0Hz,H-6 of diosgenyl),5.38(d,1H,J 7.9Hz,H-1′),5.40(s,1H,PhCH),5.57(dd,J 9.6,7.9Hz,H-2′),5.69(t,1H,J3′,4′=J4′,5′9.6Hz,H-4′),5.91(t,1H,J3′,4′=J2′,3′9.6Hz,H-3′),7.25-8.05(m,25H,Ph).元素分析Anal.Calcd for C74H82O17:C,71.48;H,6.65.Found:C,71.59;H,6.48。
(3)薯蓣苷元2,3,4,6-四-氧-苯甲酰基-β-D-葡萄吡喃糖基-(1→3)-[2,3,4-三-氧-乙酰基-α-L-鼠李吡喃糖基-(1→2)]-4,6-二-氧-苄叉基-β-D-半乳吡喃糖苷14
在0℃,氮气保护下,将化合物13(323毫克,0.26毫摩尔)和乙酰化鼠李糖亚胺酯5(126毫克,0.29毫摩尔)溶在4毫升干燥的二氯甲烷,加入5微升TMSOTf。搅拌2小时后,用三乙胺中和,减压蒸除溶剂,用硅胶柱色谱分离纯化浓缩物,以3∶1的石油醚-乙酸乙酯淋洗得到泡沫状14(329毫克,83.6%):旋光值:[α]D 25-44°(c1,CHCl3);核磁1H NMR(CDCl3):δ0.783(s,3H,CH3),0.791(d,3H,J 6.3Hz,CH3),0.97(d,3H,J 6.9Hz,CH3),1.01(s,3H,CH3),1.10(d,3H,J 5.9Hz,H-6II),2.02,2.08(2s,3×3H,3CH3CO),3.20(br s,1H,H-5I),3.38(t,1H,J 10.9Hz,H-26a),3.45-3.62(m,2H,H-3α,H-26b),3.91-4.06(m,2H,H-2I,H-6aI),4.07(dd,1H,J 9.5,3.6Hz,H-3I),4.18-4.22(m,2H,H-4I,H-6bI),4.25-4.30(m,1H,H-5III),4.37(d,1H,J 7.7Hz,H-1I),4.39-4.47(m,2H,H-5II,H-16),4.56(dd,1H,J 12.3,4.2Hz,H-6aIII),4.73(dd,J 12.2,3.3Hz,H-6bIII),5.06(t,1H,J3,4=J4,5 10.0Hz,H-4II),5.23(br s,1H,H-1II),5.27(d,1H,J7.8Hz,H-1III),5.34(dd,1H,J 10.1,3.6Hz,H-3II),5.36-3.91(m,3H,H-2II,H-6 andPhCH),5.55(dd,J 9.4,7.8Hz,H-2III),5.78(t,1H,J3,4=J4,5 9.4Hz,H-4III),5.91(t,1H,J3,4=J2,3 9.4Hz,H-3III),7.20-8.09(m,25H,Ph);13C NMR(CDCl3):14.47,16.24,17.09(2C),19.25,20.78(4C),28.76,29.35,30.24,31.34,31.39,31.80,32.08,36.90,37.16,38.17,39.70,40.22,41.57,50.06,56.25,56.46,62.07,62.56,66.17,66.31,66.79,68.88,69.04,69.67,70.08,71.39,72.22,72.43,72.86,72.98,75.77,76.89,77.62,80.76,96.82(C-1II),98.89(C-1I),99.09(C-1III),100.40(PhCH),109.24(C-22),121.62(C-6),140.52(C-5),165.18,165.39,165.47,165.93(4C,PhCO),169.98,170.05,170.44(3C,CH3CO).元素分析Anal.Calcd for C86H98O24:C,68.15;H,6.52.Found:C,68.31;H,6.46。
(4)薯蓣苷元β-D-葡萄吡喃糖基-(1→3)-[α-L-鼠李吡喃糖基-(1→2)]-β-D-半乳吡喃糖苷15
化合物14(256毫克,0.17毫摩尔)溶于20毫升80%醋酸水溶液中,加热至70℃反应。搅拌3小时后,减压蒸除溶剂,所的剩余物溶在9毫升甲醇/二氯甲烷(2∶1)混合溶剂中,加入1N氢氧化钠水溶液至pH值约9-10。室温搅拌6小时,用酸性树脂IR-120(H+)中和。抽滤,滤液浓缩,用硅胶柱色谱分离纯化浓缩物,以5∶2二氯甲烷-甲醇淋洗,得到白色固体15(113毫克,93%):核磁1H NMR(d5-pyridine):δ0.69(d,3H,J 5.1Hz,CH3),0.86(s,3H,CH3),1.04(s,3H,CH3),1.13(d,3H,J 6.9Hz,CH3),1.69(d,3H,J 6.1Hz,H-6II),3.49-3.60(m,2H),3.92-4.04(m,4H),4.18-4.26(m,3H),4.27-4.40(m,4H),4.47(dd,1H),4.52(q,1H,H-5II),4.60(dd,1H),4.68(t,1H),4.80(d,1H),4.90-4.95(m,3H,H-1I),5.20(d,1H,J 7.8Hz,H-1III),5.32(d,1H,J 4.2Hz,H-6),6.30(s,1H,H-1II).质谱ESI(-)-MS found for C45H72O17:907.5(M+Na)+。
Claims (8)
1、具有下列通式的化合物。
通式I
通式I中,R为H,Me,SO3 -或其它糖单元,R1可为H,CH3,CH2OH,CH2OSO3 -,COOH或其它糖单元,R2,R3可为H,OH,OSO3 -,或其它糖单元。
2、权利要求1的化合物,其中与薯蓣苷元相连的半乳糖的3位连接一个木糖,即通式I中R1=R2=H。
3、权利要求1的化合物,其中与薯蓣苷元相连的半乳糖的3位连接一个葡萄糖,即通式I中R1=CH2OH,R2=H,R3=OH。
4、权利要求1的化合物,其中与薯蓣苷元相连的半乳糖的3位连接另一个半乳糖,通式I中R1=CH2OH,R2=OH,R3=H。
5、权利要求1的化合物,其中与薯蓣苷元相连的半乳糖的3位连接一个岩藻糖,通式I中R1=CH3,R2=OH,R3=H。
6、权利要求1-5所述化合物作为主成分或辅助成分在抗癌药物及药物组合物中使用。
7、权利要求1-5所述化合物作为主成分或辅助成分在抗炎症药物及药物组合物中使用。
8、权利要求1-5所述化合物作为主成分或辅助成分,以口服或注射剂型在药物中的使用。
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