本发明属于医药领域，涉及一类对8-羟基鸟嘌呤dna糖基化酶1(8-hydroxytridinednaglycosylase1,ogg1)具有抑制活性的化合物，具体来说是基于ogg1抑制剂的一种天然或者修饰的梓醇衍生物及其应用。
背景技术：
氧化应激(ros)会导致各种细胞内生物大分子(包括蛋白质、脂质及核酸)的氧化。ros在dna上造成的氧化性碱基的主要类型是8-羟基鸟嘌呤(8-oxog)。8-羟基鸟嘌呤dna糖基化酶1(ogg1)是特异性修复8-oxog的修复蛋白，通过ogg1起始的碱基切除修复途径(ogg1-ber)将8-oxog识别出来并更正为正确的碱基。出乎意料的是，基因组上异常过量的8-oxog并不影响胚胎发育、癌前病变或小鼠的寿命[arai等，toxicology2006,221:179–186；leopoldo等，freeradicalbio.med.2015,8:1107–118]，而且ogg1-/-的小鼠对炎症没有明显的反应，表现为细胞内促炎因子的表达降低和炎症细胞浸润不足[mabley等，fasebj.2005,19:290–292]。进一步的机制研究表明ogg1识别启动子区氧化损伤的产物8-oxog时能够激活鸟苷三磷酸酶(gtpases)，进而通过丝裂原活化蛋白(map)激酶和磷脂酰肌醇3(pi3)激酶介导的kras-gtp信号转导和有丝分裂原应激相关激酶-1(msk1)加速核因子-κb(nf-κb)与dna的结合，促进炎症因子的释放和疾病的产生，而其他dna糖基化酶则无此作用[ba等,int.j.mol.sci.2014,15:16975-16997；aguilera-aguirre等,jimmunol.2014,193(9):4643-53；pan等,j.bio.chem.2016,291(49):25553-25566]。
同时，越来越多的证据表明ogg1抑制剂不仅具有提高某些癌症治疗疗效的潜力，而且具有主动抑制潜在耐药机制的潜力[preston等,mol.cancerther.2009,8:2015-2026；noren等,j.biol.chem.2011,286:44679-44690]。此外，ogg1的过表达逆转了ratsarcomaviraloncogenehomolog(ras)诱导的生长停滞，表明一些ras诱导的肿瘤可能依赖于ogg1活性来维持其肿瘤表型，并且ogg1抑制剂可用于治疗这些癌症[ramdzan等,plosbiol.2014,12:e1001807；nathan等，acschem.biol.2015,10,2334-2343]。因此，选择性ogg1抑制剂可以作为单药治疗或与dna损伤剂联合治疗癌症。
目前，报道的小分子ogg1抑制剂都是来源于化学合成[noren等,j.biol.chem.2011,286:44679-44690；visnes等,science2018,362(6416):834-839]。尚无来自于天然产物及其衍生物关于抑制ogg1活性的报道，受到传统清热中药的启发，梓醇衍生物特别是梓醇6位非极性取代的衍生物对ogg1具有显著的抑制活性。因此，梓醇衍生物有希望成为由ros引起的ogg1活化导致的各种炎性疾病、自身免疫性疾病的治疗药物。
梓醇衍生物主要分布于14个科50个属中的150种植物，被报道的天然梓醇类衍生物总共有146个，主要分为6位酯化梓醇衍生物和6位鼠李糖苷化梓醇衍生物两种类型，梓醇衍生物的药理活性同样非常广泛，主要有抗炎、抗氧化和抗肿瘤等药理活性，其中抗炎报道占到了37％。与此形成鲜明对比的是，在2013年报道的梓醇系统性综述中(liu等,currbioactcompd,2013,9:306-323.)，梓醇抗炎报道只占到了药理研究的11％。由于梓醇属于多羟基类环烯醚萜苷，通过常规的苷化或酯化选择性的在6位醇羟基上引入相应的基团是不现实的。通过文献调研，我们发现梓实和胡黄连中的6位酯化梓醇衍生物更加丰富。同时梓实和胡黄连中可用于结构修饰的梓苷(含量约为0.3％)和胡黄连苷ii(含量大于6％)含量更高。在碱性条件下，梓苷和胡黄连苷ii6位的酚羟基转变为芳氧负离子，增加了亲核能力，可以选择性地与卤代烃发生亲核取代反应，而结构中的醇羟基则不会发生此反应。反应在弱碱性条件下进行，既可避免了苷键的水解，也可减少酯键的断裂而减少副产物。从而保证了梓苷和胡黄连苷ii衍生物的顺利进行。
技术实现要素：
本发明的目的是为了提供一种天然梓醇衍生物或结构修饰新梓醇衍生物对新药物靶点ogg1抑制活性，为制备预防、缓解和/或治疗由ogg1活化所引起的疾病筛选新的药物。
本发明所述的具有ogg1抑制活性的天然梓醇衍生物是具有式i和式ii所示化学结构或/和其可药用衍生物：
其中，式i和式ii中的r1、r2、r3、r4、r5各自独立选自氢、烷基或酰基。所述的烷基选自c1～c4的烷基；所述的酰基选自c1～c4的酰基或选自肉桂酰基、苯环取代型肉桂酰基、苯甲酰基、苯环取代型苯甲酰基。
式i中的r1、r2、r3为氢、肉桂酰基、对羟基肉桂酰基、咖啡酸酰基、阿魏酸酰基、异阿魏酸酰基、3,4-二甲氧基肉桂酰基、苯甲酰基、对羟基苯甲酰基、香草酰基、藜芦酰基、异香草酰基、3,4-二羟基苯甲酰基，乙酰基的任意一种；式ii中的r4、r5为氢、肉桂酰基、对羟基肉桂酰基、咖啡酸酰基、阿魏酸酰基、异阿魏酸酰基、3,4-二甲氧基肉桂酰基、苯甲酰基、对羟基苯甲酰基、香草酰基、藜芦酰基、异香草酰基、3,4-二羟基苯甲酰基，乙酰基的任意一种。
作为更进一步优选方案，所述式i化合物具有如下结构式：
i-1:r1＝乙酰基,r2＝乙酰基,r3＝3,4-二甲氧基肉桂酰基
i-2:r1＝乙酰基,r2＝肉桂酰基,r3＝乙酰基
i-3:r1＝乙酰基,r2＝肉桂酰基,r3＝肉桂酰基
i-4:r1＝肉桂酰基,r2＝乙酰基,r3＝氢
i-5:r1＝氢,r2＝氢,r3＝肉桂酰基
i-6:r1＝氢,r2＝氢,r3＝对羟基肉桂酰基
i-7:r1＝氢,r2＝氢,r3＝阿魏酰基
i-8:r1＝阿魏酰基,r2＝氢,r3＝氢。
作为更进一步优选方案，所述式ii化合物具有如下结构式：
ii-1:r4＝4-羟基-3,5-二甲氧基苯甲酰基,r5＝氢
ii-2:r4＝氢,r5＝肉桂酰基
ii-3:r4＝4-羟基-3-甲氧基苯甲酰基,r5＝氢
ii-4:r4＝氢,r5＝阿魏酰基
ii-5:r4＝阿魏酰基,r5＝氢
ii-6:r4＝异阿魏酰基,r5＝氢
ii-7:r4＝4-羟基苯甲酰基,r5＝氢
ii-8:r4＝4-羟基肉桂酰基,r5＝氢
ii-9:r4＝咖啡酰基,r5＝氢。
式i所示化合物可来源于天然提取物，其中的式i-1～i-8化合物可来源于齿叶玄参(scrophulariadentataroyleexbenth.)提取物，式ii-1～ii-10化合物可来源于梓(catalpaovatag.don)或胡黄连(picrorhizascrophulariiflora.pennell)或水蔓青[veronicalinariifoliapall.cxlink.sub.dilatata(nakaietkitagawa)hong.]提取物。
本发明所述的具有ogg1抑制活性的修饰的梓醇衍生物是具有式iii和式iv所示化学结构或/和其可药用衍生物：
式iii和式iv中的r为：
具有1-12个碳原子的烷基，其为支链或非支链的，且未被取代或被以下基团取代一次或次：卤素、羟基、氰基、c1-4烷氧基、氧或它们的组合，且其中任选一个或多个-ch2ch2-基团在这种情况下被-ch＝ch-或-c≡c-取代；
或者具有3-10个碳原子的环烷基，其未被取代或被以下基团取代一次或多次：卤素、羟基、氧、氰基、具有1-4个碳原子的烷基、具有1-4个碳原子的烷氧基，或它们的组合；
或者具有4-16个碳原子的烷氧基，其未被取代或在环烷基部分和/或烷基部分被以下基团取代一次或多次：卤素、氧、氰基、羟基、c1-4-烷基、c1-4-烷氧基，或它们的组合；
或者具有6-14个碳原子的芳基，其未被取代或被以下基团取代一次或多次：卤素、cf3、ocf3、烷基、羟基、烷氧基、硝基、亚甲二氧基、亚乙二氧基、氰基，或它们的组合；
或者芳基烷基，其中芳基部分具有6-14个碳原子，而烷基部分为支链或非支链的，并具有1-5个碳原子，所述芳基烷基未被取代或在芳基部分被以下基团取代一次或多次：卤素、cf3、ocf3、烷基、羟基、烷氧基、硝基、亚甲二氧基、亚乙二氧基、氰基，或它们的组合，且其中在烷基部分中，一个或多个-ch2ch2-基团各自任选被-ch＝ch-或-c≡c-取代，且一个或多个-ch2-基团各自任选被-o-或-nh-取代，和/或烷基部分任选被卤素、氧、羟基、氰基，或它们的组合取代；
或者具有5-14个碳原子的部分不饱和碳环基团，其未被取代或被以下基团取代一次或多次：卤素、烷基、烷氧基、羟基、硝基、氰基、氧，或它们的组合；
或者杂环基，其为饱和、部分饱和或不饱和的，具有5-10个环原子，其中至少一个环原子为n、o或s原子，其未被取代或被以下基团取代一次或多次：卤素、羟基、芳基、烷基、烷氧基、氰基、三氟甲基、硝基、氧，或它们的组合；
或者杂环烷基，其中杂环部分为饱和、部分饱和或不饱和的，并具有5-10个环原子，其中至少一个环原子为n、o或s原子，且烷基部分为支链或非支链的，并具有1-5个碳原子，所述杂环烷基未被取代或在杂环部分被以下基团取代一次或多次：卤素、ocf3、羟基、芳基、烷基、烷氧基、氰基、cf3、硝基、氧，或它们的组合，其中在烷基部分中，一个或多个-ch2ch2-基团各自任选被-ch＝ch-或-c≡c-取代，且一个或多个-ch2-基团各自任选被-o-或-nh-取代，和/或烷基部分任选被卤素、氧、羟基、氰基，或它们的组合取代。
作为一种优选方案，式iii和式iv的r为：烷基、苄基、取代苄基、联苯苄基、蒽甲基、喹啉甲基、吖啶甲基或二苯甲基。
作为更进一步优选方案，所述式iii和式iv化合物具有如下结构式：
所述的可药用梓醇衍生物优选为药学上可接受的盐或溶剂化物。
本发明所述的梓醇衍生物，以梓苷和胡黄连苷ii6位选择性修饰新梓醇衍生物或/和其可药用衍生物作为活性成分用于制备预防、缓解和/或治疗由ogg1活化所引起的疾病的药物和保健食品。
进一步说，本发明所述的疾病包括但不限于：炎症疾病、自身免疫性疾病、病毒感染性疾病、肿瘤和/或它们的并发症。
本发明所述的药物可以各种给药途径给予患者，包括但不限于口服、透皮、肌肉、皮下和静脉注射。
本发明提供的梓醇衍生物对ogg1具有显著的抑制作用，在制备新型的抗炎药物方面具有良好的应用前景。本发明所公开的基于梓苷和胡黄连苷ii结构修饰的梓醇衍生物的制备方法，为首次合成，与从植物中寻找显著抑制ogg1活性的梓醇衍生物相比，更加快捷高效。
本发明和已有技术相比，其技术进步是显著的。实验证明本发明所述的式(i)、式(ii)、式(iii)和式(iv)化合物或其水合物、药学上可接受的盐、互变异构体、立体异构体、前体化合物对8-羟基鸟嘌呤dna糖基化酶1(8-hydroxytridinednaglycosylase1,ogg1)具有显著的抑制抑制，在制备抗炎药物和抗肿瘤药物上有着广阔的应用空间。
具体实施方式
下面结合实施例对本发明作进一步详细、完整地说明，但并不因此限制本发明；本领域的技术人员根据下述内容所作的一些非本质的改进或替换均属于本发明的保护范围。
下列实施例中未注明具体条件的实验方法，通常按照常规条件或按照制造厂商所建议的条件。
实施例1：式i天然梓醇衍生物的制备
将4.1kg齿叶玄参药材用体积分数为95％的乙醇水溶液回流提取3次，每次回流2小时，每次用乙醇水溶液40l，合并提取液，减压浓缩得浸膏(约570g)；向该浸膏中加约3倍量(1500ml)水混悬后，依次用石油醚(1500ml×3)、乙酸乙酯(1500ml×3)萃取，收集乙酸乙酯萃取液；减压回收乙酸乙酯后进行硅胶柱层析，依次用石油醚和乙酸乙酯进行梯度洗脱(10:1～0:1)；将所得流分用硅胶柱层析：先用石油醚-乙醇混合溶剂进行梯度洗脱(体积比由10:1至3:1)，然后用反向柱层析：用甲醇水溶液进行梯度洗脱(甲醇的体积分数由50％至70％)，最后用sephadexlh-20分离纯化(洗脱剂为甲醇)，即得化合物i-1至i-8，均为白色固体粉末。
化合物i-1
1hnmr(400mhz,cd3od)：δh6.40(1h,dd,j＝1.5/5.9hz,3-h)，2.49(1h,m,5-h)，4.07(1h,d,j＝8.1hz,6-h)，3.67(1h,brs,7-h)，2.59(1h,dd,j＝7.7/9.6hz,9-h)，4.16(1h,d,j＝13.1hz,10β-h)，3.82(1h,d,j＝13.1hz,10α-h)，4.77(1h,d,j＝7.9hz,1′-h)，3.40(1h,t,j＝9.0hz,3′-h)，3.92(1h,dd,j＝1.9/11.9hz,6′β-h)，3.62(1h,dd,j＝6.6/11.9hz,6′α-h)，5.31(1h,dd,j＝3.4/1.7hz,2″-h)，5.36(1h,dd,j＝3.4/10.0hz,3″-h)，5.17(1h,t,j＝10.0hz,4″-h)，4.07(1h,dd,j＝6.2/10.0hz,5″-h)，1.22(3h,d,j＝6.2hz,6″-h)，7.67(1h,d,j＝15.9hz,7″′-h)，6.42(1h,d,j＝15.9hz,8″′-h)，7.24(1h,d,j＝1.9hz,h-2″′)，6.98(1h,d,j＝8.4hz,h-5″′)，7.19(1h,dd,j＝1.9/8.4hz,h-6″′)，2.17(3h,s,come)，1.93(3h,s,come)，3.87(3h,s,ome)，3.87(3h,s,ome′)；13c-nmr(100mhz,cd3od)：δc95.3(c-1)，142.7(c-3)，103.3(c-4)，37.3(c-5)，85.0(c-6)，59.6(c-7)，66.7(c-8)，43.4(c-9)，61.6(c-l0)，99.9(c-l′)，75.0(c-2′)，77.8(c-3′)，72.0(c-4′)，78.8(c-5′)，63.1(c-6′)，97.9(c-1")，71.4(c-2")，70.8(c-3")，72.1(c-4")，68.4(c-5")，17.9(c-6")，128.7(c-l′")，111.7(c-2"′)，151.0(c-3"′)，153.3(c-4"′)，112.7(c-5"′)，124.5(6′")，147.8(c-7),115.5(c-8)，168.1(s,co)，171.8&171.8(come×2)，20.8(come×2)，56.6(ome)，56.7(ome′)。
esi-ms(pos.)：805[m+na]+，esi-ms(neg.)：827[m+hcoo-]-。
上述数据分析结果与文献(fitoterapia,2014,98:84–90)中报道的scrodentosidea一致。
化合物i-2
esi-ms(pos.)：745[m+na]+，761[m+k]+，esi-ms(neg.)：767[m+hcoo-]-，1443[2m-h]-。1hnmr(400mhz,cd3od)：δh6.40(1h,dd,j＝1.3/6.0hz,3-h)，2.50(1h,m,5-h)，4.07(1h,d,j＝7.6hz,6-h)，3.68(1h,brs,7-h)，2.59(1h,dd,j＝6.0/9.5hz,9-h)，4.15(1h,d,j＝13.1hz,10β-h)，3.82(1h,d,j＝13.1hz,10α-h)，4.78(1h,d,j＝8.0hz,1′-h)，3.40(1h,t,j＝9.0hz,3′-h)，3.92(1h,dd,j＝1.7/11.9hz,6′β-h)，3.63(1h,dd,j＝6.6/11.9hz,6′α-h)，5.39(1h,dd,j＝3.5/9.9hz,3″-h)，5.15(1h,t,j＝9.9hz,4″-h)，4.04(1h,dd,j＝6.2/9.9hz,5″-h)，1.22(3h,d,j＝6.2hz,6″-h)，7.65(1h,d,j＝16.1hz,7″′-h)，6.44(1h,d,j＝16.1hz,8″′-h)，7.60(2h,m,h-2″′,6″′)，7.41(3h,m,h-3″′,h-4″′,h-5″′)，2.04(3h,s,come)，2.16(3h,s,come)；13c-nmr(100mhz,cd3od)：δc95.2(c-1)，142.6(c-3)，103.3(c-4)，37.3(c-5)，85.0(c-6)，59.5(c-7)，66.7(c-8)，43.4(c-9)，61.5(c-l0)，99.7(c-l′)，74.9(c-2′)，77.8(c-3′)，72.4(c-4′)，78.8(c-5′)，63.1(c-6′)，97.8(c-1")，71.4(c-2")，70.9(c-3")，71.9(c-4")，68.2(c-5")，17.9(c-6")，135.6(c-l′")，130.2(c-2"′,6′")，129.5(c-3",c-5")，131.9(c-4")，147.5(c-7),118.0(c-8)，167.3(s,co)，171.7&171.9(come×2)，20.9(come×2)；
上述数据分析结果与文献(j.nat.prod.,1993,56:606-609.)中报道的scropoliosided一致。
化合物i-3
esi-ms(pos.)：833[m+na]+；esi-ms(neg.)：855[m+hcoo-]-。1hnmr(400mhz，cd3od)：δh6.41(1h,dd,j＝1.5/5.9hz,3-h)，2.53(1h,m,5-h)，4.10(1h,d,j＝8.2hz,6-h)，3.70(1h,brs,7-h)，2.61(1h,dd,j＝7.8/9.6hz,9-h)，4.18(1h,d,j＝13.1hz,10β-h)，3.84(1h,d,j＝13.1hz,10α-h)，4.79(1h,d,j＝7.9hz,1′-h)，3.41(1h,dd,j＝8.9hz,3′-h)，3.93(1h,dd,j＝1.8/11.9hz,6′β-h)，3.64(1h,dd,j＝6.6/11.9hz,6′α-h),5.41(1h,dd,j＝1.7/3.4hz,2″-h)，5.51(1h,dd,j＝3.4/10.2hz,3″-h)，5.30(1h,t,j＝10.2hz,4″-h)，4.15(1h,dd,j＝6.2/10.2hz,5″-h)，1.26(3h,d,j＝6.2hz,6″-h)，7.61(1h,d,j＝16.0hz,7″′-h)，6.40(1h,d,j＝16.0hz,8″′-h)，7.54(2h,m,h-2″′,6″′)，7.41(6h,m,h-3″′,3″″,h-4″′,4″″,h-5″′,5″″)，7.70(1h,d,j＝16.0hz,7″″-h)，6.50(1h,d,j＝16.0hz,8″″-h)，7.51(2h,m,h-2″″,6″″)，2.18(3h,s,come)；13cnmr(100mhz,cd3od)：δc95.2(c-1)，142.6(c-3)，103.4(c-4)，37.3(c-5)，85.1(c-6)，59.6(c-7)，66.7(c-8)，43.5(c-9)，61.6(c-l0)，99.9(c-l′)，75.0(c-2′)，7.8(c-3′)，72.6(d,c-4′)，78.8(c-5′)，63.1(c-6′)，97.9(c-1")，71.6(c-2")，70.9(c-3")，71.9(c-4")，68.4(c-5")，18.0(c-6")，135.6(c-l′",1″″)，130.1(c-2"′,2″″andc-6′",6″″)，129.5(c-3"′,3″″和c-5"′,5″″)，131.9(d,c-4"′,4″″)，147.5(c-7″′or7″″)，147.8(c-7″′or7″″)，118.0(c-8″′,8″″)，167.4(c-9″′或9″″)，167.8(c-9″′或9″″)，171.8(come)，20.9(come)。
上述数据分析结果与文献(plantamedica,1988,54(2):168-170.)中报道的scropoliosideb一致。
化合物i-4
esi-ms(pos.)：703[m+na]+；esi-ms(neg.)：725[m+hcoo-]-。1hnmr(400mhz，cd3od)：δh6.39(1h,dd,j＝6.0/1.5hz,h-3)，2.49(1h,m,h-5)，4.06(1h,d,j＝8.2hz,h-6)，2.58(1h,dd,j＝9.5/7.6hz,h-9)，4.15(1h,d,j＝13.1hz,h-10a)，3.82(1h,d,j＝13.1hz,h-10b)，4.78(1h,d,j＝7.9hz,h-1′)，3.42(1h,t,j＝8.9hz,h-3′)，3.92(1h,j＝12.1/2.0hz,h-6′b)，5.03(1h,brs,h-1″)，5.32(1h,dd,j＝3.4/1.7hz,h-2″)，5.23(1h,dd,j＝9.9/3.4hz,h-3″)，1.33(3h,d,j＝6.2hz,h-6″)，7.61(2h,m,h-2″′,6″′)，7.41(3h,m,h-3″′,4″′,5″′)，7.71(1h,d,j＝16.0hz,h-7″′)，6.52(1h,d,j＝16.0hz,h-8″′)，2.12(come,s)，5.03-5.13(3h,m,h-1,4,1″)，3.60-3.67(3h,m,h-7,6′a,5″)，3.23-3.31(4h,m,h-2′,4′,5′,4″)。
上述数据分析结果与文献(phytochemistry,1995,40(5):1569-1571.)中报道的scorodioside一致。
化合物i-5
esi-ms(pos.)：661[m+na]+；esi-ms(neg.)：683[m+hcoo-]-。1hnmr(400mhz,cd3od)：δh6.39(1h,dd,j＝1.6/6.2hz,h-3)，2.43(1h,m,h-5)，4.04(1h,d,j＝7.7hz,h-6)，3.66(1h,brs,h-7)，2.57(1h,dd,j＝8.1/9.5hz,h-9)，4.15(1h,d,j＝13.2hz,h-10a)，3.82(1h,d,j＝13.2hz,h-10b)，4.77(1h,d,j＝8.1hz,h-1′)，3.40(1h,t,j＝9.1hz,h-3′)，3.62(1h,dd,j＝6.4/12.1hz,h-6′α)，5.00(1h,brs,h-1″)，1.18(3h,d,j＝6.2,h-6″)，7.62(2h,m,h-2″′,6″′)，7.41(3h,m,h-3″′,4″′,5″′)，7.74(1h,d,j＝16.0hz,h-7″′)，6.58(1h,d,j＝16.0hz,h-8″′)，5.05-5.12(3h,m,h-1,h-4,h-4″)，3.20-3.31(4h,h-2′,4′,5′,3″)，3.89-3.94(4h,h-6′β,2″,5″)。
上述数据分析结果与文献(phytochemistry,1999,50:619-627.)中报道的6-o-α-l-(4″-o-trans-cinnamoyl)rhamnopyranosylcatalpol一致。
化合物i-6
esi-ms(pos.)：721[m+na]+；esi-ms(neg.)：743[m+hcoo-]-。1hnmr(400mhz，cd3od)：δh6.39(1h,dd,j＝1.6/6.0hz,h-3)，2.42(1h,m,h-5)，4.04(1h,d,j＝8.3hz,h-6)，3.66(1h,brs,h-7)，2.59(1h,dd,j＝7.8/9.6hz,h-9)，4.16(1h,d,j＝13.1hz,h-10β)，3.82(1h,d,j＝13.1hz,h-10α)，4.77(1h,d,j＝7.9hz,h-1′)，3.40(1h,t,j＝9.0hz,h-3′)，3.62(1h,dd,j＝6.6/12.0hz,h-6′α)，5.00(1h,d,j＝1.0hz,h-1″)，1.18(3h,d,j＝6.3hz,h-6″)，7.68(1h,d,j＝16.0hz,h-7″′)，6.47(1h,d,j＝16.0hz,h-8″′)，7.24(1h,d,j＝1.8hz,h-2″′)，6.98(1h,d,j＝8.3hz,h-5″′)，7.20(1h,dd,j＝1.8/8.3hz,h-6″′)，3.87(6h,s,ome×2)，5.05-5.11(3h,h-1,h-4,h-4″)，3.23-3.31(3h,h-2′,4′,5′)，3.89-3.94(4h,h-6′β,2”,3″,5″)。
上述数据分析结果与文献(phytochemistry,1999,50:619-627.)中报道的lagotisosided一致。
化合物i-7
esi-ms(pos.):707[m+na]+,esi-ms(neg.):683[m-h]-.1hnmr(400mhz,cd3od):δh6.38(1h,brd,j＝5.7hz,h-3),2.42(1h,m,h-5),4.03(1h,d,j＝8.1hz,h-6),3.66(1h,brs,h-7),2.57(1h,dd,j＝8.0/9.0hz,h-9),4.16(1h,d,j＝13.1hz,h-10a),3.82(1h,d,j＝13.1hz,h-10b),4.78(1h,d,j＝7.9hz,h-1′),3.41(1h,t,j＝9.0hz,h-3′),3.63(1h,dd,j＝6.6/11.8hz,h-6′a),4.99(1h,brs,h-1″),1.18(3h,d,j＝6.2hz,h-6″),7.21(1h,s,h-2″′),6.82(1h,d,j＝8.0hz,h-5″′),7.10(1h,d,j＝8.0hz,h-6″′),7.65(1h,d,j＝15.9hz,h-7″′),6.41(1h,d,j＝15.9hz,h-8″′),5.05-5.10(3h,m,h-1,h-4,h-4″),3.20-3.35(4h,h-2′,4′,5′,3″),3.86-3.94(4h,h-6′b2″,5″).13cnmr(100mhz,cd3od):δc95.3(c-1),142.5(c-3),103.6(c-4),37.4(c-5),84.2(c-6),59.6(c-7),66.7(c-8),43.4(c-9),61.6(c-l0),99.8(c-l′),74.9(c-2′),77.8(c-3′),71.9(c-4′),78.7(c-5′),63.1(c-6′),100.6(c-1"),72.6(c-2"),70.4(c-3"),75.4(c-4"),68.4(c-5"),18.0(c-6"),127.9(c-1″′),111.9(c-2″′),150.8(c-3″′),149.5(c-4″′),115.6(c-5″′),124.3(c-6″′),147.3(c-7″′),116.6(c-8″′),169.0(c-9″′),56.6(ome).
上述数据分析结果与文献(phytochemistry,1991,30(6):1917-1920.)中报道的6-o-α-l-(4”-o-feruloyl)rhamnopyranosylcatalpol一致。
化合物i-8
esi-ms(pos.):707[m+na]+,esi-ms(neg.):683[m-h]-.1hnmr(400mhz,cd3od):δh6.39(1h,dd,j＝6.0/1.7hz,h-3),2.45(1h,m,h-5),4.04(1h,d,j＝8.2hz,h-6),3.67(1h,brs,h-7),2.59(1h,dd,j＝7.8/8.9hz,h-9),4.17(1h,d,j＝13.1hz,h-10a),3.82(1h,d,j＝13.1hz,h-10b),4.79(1h,d,j＝7.9hz,h-1′),3.42(1h,t,j＝9.0hz,h-3′),3.64(1h,dd,j＝6.7/11.9hz,h-6′a),5.05(1h,d,j＝1.3hz,h-1″),5.17(1h,dd,j＝3.4/1.3hz,h-2″),3.95(1h,dd,j＝3.4/9.6hz,h-3″),3.51(1h,t,j＝9.6hz,h-4″),3.77(1h,dd,j＝9.6/6.2hz,h-5″),1.33(3h,d,j＝6.2hz,h-6″),7.24(1h,d,j＝1.5hz,h-2″′),6.84(1h,d,j＝8.3hz,h-5″′),7.11(1h,dd,j＝8.3/1.5hz,h-6″′),7.68(1h,d,j＝15.9hz,h-7″′),6.46(1h,d,j＝15.9hz,h-8″′),3.92(3h,s,ome)；13cnmr(100mhz,cd3od):δc95.3(c-1),142.4(c-3),103.6(c-4),37.4(c-5),84.5(c-6),59.6(c-7),66.7(c-8),43.4(c-9),61.6(c-l0),99.8(c-l′),75.0(c-2′),77.8(c-3′),71.9(c-4′),78.7(c-5′),63.1(c-6′),97.8(c-1"),74.4(c-2"),70.7(c-3"),74.3(c-4"),70.4(c-5"),18.2(c-6"),127.9(c-1″′),111.8(c-2″′),150.9(c-3″′),149.5(c-4″′),115.4(c-5″′),124.5(c-6″′),147.6(c-7″′),116.6(c-8″′),168.8(c-9″′),56.6(ome).
上述数据分析结果与文献(journalofnaturalproducts.1990,53:107-111)中报道的6-o-α-l-(2”-o-feruloyl)rhamnopyranosylcatalpol一致。
实施例2：式ii天然梓醇衍生物的制备
胡黄连根茎1kg，粉碎为粗粉，用10倍量甲醇加热回流提取3次，浓缩后加200-300目硅胶拌样，用300-400目硅胶柱层析，经氯仿-甲醇(1:20-1:5)梯度洗脱，得到2个流份。其中流份2用反相ods柱层析，经甲醇-水(10％-30％)梯度洗脱，所得胡黄连苷ii流份进行sephadexlh-20柱纯化(50％甲醇)，分离得到ii-1～ii-6，均为白色粉末。
梓实10kg，粉碎为粗粉，用10倍量75％乙醇加热回流提取3次，每次2h，提取液经减压回收乙醇至无醇味，用等量二氯甲烷萃取3次脱脂。剩余水层浓缩至一定体积后，通过d101大孔树脂柱进行初步分离，分别收集水、20％乙醇、40％乙醇、60％乙醇、80％乙醇、95％乙醇洗脱流份，40％和60％乙醇洗脱流份分别通过硅胶柱色谱、mci柱色谱、sephadexlh-20柱色谱、ods柱色谱共分离得到ii-5，ii-7，ii-8，ii-9，均为白色粉末。
将15kg水蔓菁药材用体积分数为95％的乙醇水溶液回流提取3次，每次回流2小时，每次用乙醇水溶液75l，合并提取液，减压浓缩得浸膏(约5.6kg)；向该浸膏中加约5倍量(30l)水混悬后，用二氯甲烷(20l×3)萃取，得水层于二氯甲烷层。将水层浓缩至10l上大孔树脂梯度洗脱，梯度为水，20％乙醇，40％乙醇，60％乙醇，80％乙醇，95％乙醇，每个梯度75l。对40％乙醇洗脱部位(约795g)进行分离，减压回收40％乙醇洗脱部位后进行硅胶柱层析，依次用二氯甲烷和甲醇进行梯度洗脱(20:1～0:1)；将所得流分用反相层析：先用mci层析(甲醇体积分数30％,35％,40％)，后用ods柱层析(甲醇体积分数25％,27.5％，30％,32.5％,35％)，最后用sephadexlh-20纯化，(洗脱剂为甲醇-水＝1：1)，即得化合物1，2，3，4，5；对水洗脱部位(约1265g)进行分离，减压回收部分水洗脱部位后进行硅胶柱层析，依次用乙酸乙酯和甲醇进行梯度洗脱(50:1～0:1)；将所得流分用反相层析：先用mci层析(甲醇体积分数0％,5％,10％)，后用sephadexlh-20纯化，(洗脱剂为甲醇-水或二氯甲烷-甲醇＝1：1)，即得化合物ii-3，ii-5，ii-8，ii-9，ii-10，均为白色粉末。
化合物ii-1
esi-ms(pos.):565[m+na]+,esi-ms(neg.):541[m-h-]-.molecularformula:c24h30o14,molecularweight:542。1hnmr(500mhz,cd3od)：δh5.11(1h,d,j＝9.6hz,h-1),6.43(1h,brd,j＝5.9hz,h-3),4.98(1h,dd,j＝5.9/5.0hz,h-4),2.60(1h,m,h-5),5.07(1h,brd,j＝8.1hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,d,j＝13.2hz,h-10a),3.74(1h,m,h-10b),4.62(1h,d,j＝7.8hz,h-1′),3.43(1h,dd,j＝6.9/11.7hz,h-6′a),7.25(1h,s,h-2″,6″),3.82(6h,ome×2).13cnmr(125mhz,cd3od):δc93.0(c-1),141.1(c-3),101.9(c-4),35.2(c-5),79.9(c-6),58.3(c-7),65.9(c-8),41.8(c-9),58.5(c-l0),97.9(c-l′),73.5(c-2′),76.4(c-3′),70.3(c-4′),77.5(c-5′),61.4(c-6′),118.6(c-1″),107.1(c-2″,6″),147.7(c-3″,5″),141.3(c-4″),165.7(c-7″),56.1(ome×2).
上述数据分析结果与文献(中华中医药杂志,2017,32(5):2070-2074.)中报道的胡黄连苷ⅵ一致。
化合物ii-2
esi-ms(pos.):510[m+nh4]+,esi-ms(neg.):551[m+ch3coo-]-.1hnmr(600mhz,cd3od):δh4.88(1h,m,h-1),6.32(1h,dd,j＝1.4/6.0hz,h-3),5.02(1h,dd,j＝6.0/5.0hz,h-4),2.24(1h,m,h-5),3.79(1h,brd,j＝8.0hz,h-6),3.41(1h,brs,h-7),2.54(1h,dd,j＝9.6/7.9hz,h-9),4.16(1h,d,j＝13.0hz,h-10a),3.66(1h,d,j＝13.0hz,h-10b),4.79(1h,d,j＝7.9hz,h-1′),3.29(1h,m,h-2′),3.43(2h,m,h-3′,4′),3.56(1h,m,h-5′),4.45(1h,dd,j＝5.6/11.9hz,h-6′a),4.53(1h,dd,j＝11.9/2.0hz,h-6′b),7.62(2h,m,h-2″,6″),7.41(3h,m,h-3″,4″,5″),7.71(1h,d,j＝16.0hz,h-7″),6.56(1h,d,j＝16.0hz,h-8″).13cnmr(150mhz,cd3od):δc95.4(c-1),141.9(c-3),104.2(c-4),39.2(c-5),79.8(c-6),62.5(c-7),66.2(c-8),43.5(c-9),62.0(c-l0),99.9(c-l′),74.9(c-2′),77.6(c-3′),71.7(c-4′),76.0(c-5′),64.3(c-6′),135.7(c-1″),130.2(c-2″,6″),129.5(c-3″,5″),131.8(c-4″),146.8(c-7″),118.8(c-8″),168.5(c-9″)。
上述数据分析结果与文献(中国天然产物,2006,4(1):36-39.)中报道的胡黄连苷i一致。
化合物ii-3
esi-ms(pos.):530[m+nh4]+,esi-ms(neg.):511[m-h-]-.1hnmr(600mhz,cd3od)：δh5.20(1h,d,j＝9.2hz,h-1),6.38(1h,dd,j＝1.2/5.9hz,h-3),5.01(1h,dd,j＝5.9/4.2hz,h-4),2.59(1h,m,h-5),5.13(1h,brd,j＝7.1hz,h-6),3.75(1h,brs,h-7),2.63(1h,m,h-9),4.19(1h,d,j＝13.2hz,h-10a),3.85(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.9hz,h-1′),3.27(2h,m,h-2′,4′),3.33(1h,m,h-5′),3.41(1h,t,j＝9.0hz,h-3′),3.65(1h,dd,j＝6.8/12.0hz,h-6′a),3.95(1h,dd,j＝1.9/12.0hz,h-6′b),7.57(1h,d,j＝1.8hz,h-2″),6.86(1h,d,j＝8.3hz,h-5″),7.60(1h,dd,j＝8.3/1.8hz,h-6″),3.91(3h,s,och3).13cnmr(150mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),81.9(c-6),60.4(c-7),67.0(c-8),43.3(c-9),61.4(c-l0),99.8(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),122.2(c-1″),113.7(c-2″),153.2(c-3″),149.0(c-4″),116.1(c-5″),125.5(c-6″),168.0(c-7″),56.6(och3)。
上述数据分析结果与文献(中国医药工业杂志,2007,38(3):221-226)中报道的胡黄连苷ii一致。
化合物ii-4
esi-ms(pos.):556[m+nh4]+,esi-ms(neg.):537[m-h-]-.1hnmr(600mhz,cd3od):δh4.86(1h,m,h-1),6.32(1h,dd,j＝1.7/6.0hz,h-3),5.02(1h,dd,j＝6.0/4.8hz,h-4),2.23(1h,m,h-5),3.79(1h,brd,j＝8.1hz,h-6),3.41(1h,brs,h-7),2.54(1h,dd,j＝9.7/7.7hz,h-9),4.16(1h,d,j＝13.0hz,h-10a),3.66(1h,d,j＝13.0hz,h-10b),4.78(1h,d,j＝7.9hz,h-1′),3.29(1h,m,h-2′),3.42(2h,m,h-3′,4′),3.55(1h,ddd,j＝8.2/5.6/2.3hz,h-5′),4.45(1h,dd,j＝5.6/11.9hz,h-6′a),4.50(1h,dd,j＝11.9/2.3hz,h-6′b),7.20(1h,d,j＝1.8hz,h-2″),7.08(1h,dd,j＝8.2/1.8hz,h-5″),6.82(1h,d,j＝8.2hz,h-6″),7.62(1h,d,j＝15.9hz,h-7″′),6.39(1h,d,j＝15.9hz,h-8″),3.90(3h,s,och3).13cnmr(150mhz,cd3od):δc95.5(c-1),141.9(c-3),104.2(c-4),39.3(c-5),79.8(c-6),62.6(c-7),66.3(c-8),43.5(c-9),62.0(c-l0),99.9(c-l′),74.9(c-2′),77.6(c-3′),71.7(c-4′),76.1(c-5′),64.1(c-6′),127.7(c-1″),111.8(c-2″),149.6(c-3″),150.9(c-4″),116.7(c-5″),124.4(c-6″),147.3(c-7″),115.4(c-8″),169.1(c-9″),56.6(och3).
上述数据分析结果与文献(journalofnaturalproducts,1980,43(6):649-707)中报道的胡黄连苷iii一致。
化合物ii-5
esi-ms(pos.):556[m+nh4]+,esi-ms(neg.):537[m-h-]-.1hnmr(600mhz,cd3od)：δh5.17(1h,d,j＝9.1hz,h-1),6.38(1h,dd,j＝1.2/5.9hz,h-3),4.99(1h,dd,j＝5.9/4.4hz,h-4),2.61(2h,m,h-5,9),5.03(1h,brd,j＝7.8hz,h-6),3.71(1h,brs,h-7),4.17(1h,d,j＝13.2hz,h-10a),3.84(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.9hz,h-1′),3.27(2h,m,h-2′,4′),3.31(1h,m,h-5′),3.41(1h,t,j＝9.1hz,h-3′),3.65(1h,dd,j＝6.8/12.0hz,h-6′a),3.93(1h,dd,j＝1.8/12.0hz,h-6′b),7.22(1h,d,j＝1.6hz,h-2″),6.82(1h,d,j＝8.1hz,h-5″),7.10(1h,dd,j＝8.1/1.6hz,h-6″),7.67(1h,d,j＝15.9hz,h-7″),6.43(1h,d,j＝15.9hz,h-8″),3.90(3h,s,och3).13cnmr(150mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),81.5(c-6),60.4(c-7),67.0(c-8),43.3(c-9),61.4(c-l0),99.8(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),127.8(c-1″),111.9(c-2″),149.5(c-3″),151.0(c-4″),116.6(c-5″),124.5(c-6″),147.6(c-7″),115.0(c-8″),169.1(c-9″),56.6(och3)。
上述数据分析结果与文献(plantamedica,1989,55(5):467-469)中报道的6-o-e-feruloylcatalpol一致。
化合物ii-6
esi-ms(pos.):556[m+nh4]+,esi-ms(neg.):537[m-h-]-.1hnmr(600mhz,cd3od)：δh5.17(1h,d,j＝9.2hz,h-1),6.38(1h,dd,j＝1.6/5.8hz,h-3),4.99(1h,dd,j＝5.8/4.2hz,h-4),2.60(1h,m,h-5),5.04(1h,dd,j＝7.9/1.1hz,h-6),3.71(1h,d,j＝1.1hz,h-7),2.63(1h,dd,j＝9.2/7.7hz,h-9),4.17(1h,d,j＝13.2hz,h-10a),3.84(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.9hz,h-1′),3.27(2h,m,h-2′,4′),3.34(1h,m,h-5′),3.41(1h,t,j＝9.0hz,h-3′),3.65(1h,dd,j＝6.7/12.0hz,h-6′a),3.93(1h,dd,j＝2.1/12.0hz,h-6′b),7.09(1h,d,j＝2.1hz,h-2″),6.94(1h,d,j＝8.4hz,h-5″),7.05(1h,dd,j＝8.4/2.1hz,h-6″),7.63(1h,d,j＝15.9hz,h-7″′),6.37(1h,d,j＝15.9hz,h-8″),3.89(3h,s,och3).13cnmr(150mhz,cd3od):δc95.2(c-1),142.5(c-3),103.1(c-4),36.9(c-5),81.5(c-6),60.4(c-7),67.0(c-8),43.3(c-9),61.4(c-l0),99.8(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),128.9(c-1″),115.1(c-2″),148.9(c-3″),152.1(c-4″),112.6(c-5″),115.5(c-6″),147.5(c-7″),122.8(c-8″),169.0(c-9″),56.5(och3)。
上述数据分析结果与文献(helveticachimicaacta,1979,62(2):535-539.)中报道的米内苷(minecoside)一致。
化合物ii-7
esi-ms(pos.):500[m+nh4]+,esi-ms(neg.):481[m-h-]-.molecularformula:c22h26o12,molecularweight:482。1hnmr(600mhz,cd3od)：δh5.15(1h,d,j＝9.1hz,h-1),6.34(1h,dd,j＝1.2/6.0hz,h-3),4.96(1h,dd,j＝6.0/4.1hz,h-4),2.63(1h,m,h-5),5.07(1h,brd,j＝6.9hz,h-6),3.71(1h,brs,h-7),2.59(1h,m,h-9),4.15(1h,d,j＝13.2hz,h-10a),3.81(1h,d,j＝13.2hz,h-10b),4.77(1h,d,j＝7.9hz,h-1′),3.26(2h,m,h-2′,4′),3.30(1h,m,h-5′),3.39(1h,t,j＝9.1hz,h-3′),3.62(1h,dd,j＝6.6/12.0hz,h-6′a),3.90(1h,dd,j＝1.8/12.0hz,h-6′b),7.87(2h,d,j＝8.8hz,h-2″,6″),6.81(2h,d,j＝8.8hz,h-3″,5″).13cnmr(150mhz,cd3od):δc95.2(c-1),142.5(c-3),103.1(c-4),36.8(c-5),81.7(c-6),60.4(c-7),67.0(c-8),43.3(c-9),61.4(c-l0),99.8(c-l′),74.9(c-2′),78.7(c-3′),71.8(c-4′),77.8(c-5′),63.0(c-6′),121.8(c-1″),133.1(c-2″,6″),116.4(c-3″,5″),163.9(c-4″),168.0(c-7″).
上述数据分析结果与文献(中成药,2012,34(12):2381-2384.)中报道的梓苷一致。
化合物ii-8
esi-ms(pos.):526[m+nh4]+,esi-ms(neg.):507[m-h-]-.molecularformula:c24h28o12，molecularweight:508。1hnmr(600mhz,c5d5n):δh5.57(1h,m,h-1),6.47(1h,dd,j＝5.7hz,h-3),5.12(1h,dd,j＝5.9/3.6hz,h-4),2.93(2h,m,h-5,9),5.29(1h,d,j＝6.7hz,h-6),3.99(1h,brs,h-7),4.57(1h,d,j＝13.3hz,h-10a),4.46(1h,d,j＝13.3hz,h-10b),5.57(1h,d,j＝7.8hz,h-1′),4.18(1h,dd,j＝7.8,9.0hz,h-2′),4.34(1h,t,j＝9.1hz,h-3′),4.27(1h,t,j＝9.0hz,h-4′),4.06(1h,m,h-5′),4.39(1h,dd,j＝11.9/5.4hz,h-6′a),4.55(1h,dd,j＝11.9/2.0hz,h-6′b),7.63(2h,d,j＝8.5hz,h-2″,6″),7.19(2h,d,j＝8.5hz,
h-3″,5″),8.00(1h,d,j＝15.9hz,h-7″,),6.61(1h,d,j＝15.9hz,h-8″).13cnmr(150mhz,c5d5n):δc95.0(c-1),141.9(c-3),102.8(c-4),36.7(c-5),80.7(c-6),59.8(c-7),67.3(c-8),43.5(c-9),60.5(c-l0),100.5(c-l′),75.4(c-2′),79.5(c-3′),71.8(c-4′),78.7(c-5′),62.9(c-6′),126.3(c-1″),131.2(c-2″,6″),117.2(c-3″,5″),162.0(c-4″),146.3(c-7″),114.8(c-8″),167.7(c-9″).
以上述数据分析结果与文献(中草药,1994,25(5):227-228.)中报道的specioside一致。
化合物ii-9
esi-ms(pos.):525[m+h]+,esi-ms(neg.):1047[2m-h-]-.molecularformula:c24h28o13，molecularweight:524.1hnmr(400mhz,cd3od),δh5.17(1h,d,j＝9.2hz,h-1),6.37(1h,brd,j＝6.0hz,h-3),4.98(1h,dd,j＝6.0/4.2hz,h-4),2.62(2h,m,h-5,9),5.03(1h,brd,j＝7.5hz,h-6),3.70(1h,brs,h-7),4.17(1h,d,j＝13.2hz,h-10a),3.83(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.8hz,h-1′),3.27(2h,m,h-2′,4′),3.42(1h,t,j＝8.9hz,h-3′),3.65(1h,dd,j＝6.5/12.0hz,h-6′a),3.93(1h,brd,j＝12.0hz,h-6′b),7.07(1h,d,j＝1.2hz,h-2″),6.79(1h,d,j＝8.1hz,h-5″),6.97(1h,dd,j＝8.1/1.2hz,h-6″),7.60(1h,d,j＝15.9hz,h-7″′),6.32(1h,d,j＝15.9hz,h-8″).13cnmr(100mhz,cd3od),δc95.2(c-1),142.5(c-3),103.1(c-4),36.9(c-5),81.4(c-6),60.4(c-7),67.0(c-8),43.3(c-9),61.4(c-l0),99.8(c-l′),75.0(c-2′),78.7(c-3′),71.9(c-4′),77.8(c-5′),63.0(c-6′),127.8(c-1″),114.6(c-2″),146.9(c-3″),149.9(c-4″),116.7(c-5″),123.3(c-6″),147.8(c-7″),115.3(c-8″),169.1(c-9″).
上述数据分析结果与文献(journalofnaturalproducts.1980,43(6):649-707.)中报道的6-o-咖啡酰基梓醇(nudifloside/verminoside)一致。
esi-ms(pos.)：516[m+nh4]+；esi-ms(neg.)：497[m-h-]-。1hnmr(600mhz，cd3od):δh5.19(1h,d,j＝9.2hz,h-1),6.38(1h,d,j＝5.7hz,h-3),5.00(1h,dd,j＝3.7/5.9hz,h-4),2.65(1h,d,j＝2.1hz,h-5),5.09(1h,d,j＝6.9hz,h-6),3.74(1h,d,j＝1.0hz,h-7),2.62(1h,d,j＝7.5hz,h-9),4.18(1h,d,j＝13.2hz,h-10a),3.84(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.9hz,h-1’),3.25～3.46(4h,m,h-2’,3’,4’,5’),3.93(1h,dd,j＝1.9/11.9hz,h-6’a),3.65(1h,dd,j＝6.6/12.0hz,h-6’b),7.47(1h,m,h-2”),6.82(1h,d,j＝8.8hz,h-5”),7.46(1h,m,h-6”)；13cnmr(150mhz，cd3od):δc95.1(c-1),142.4(c-3),103.0(c-4),36.8(c-5),81.6(c-6),60.3(c-7),66.8(c-8),43.2(c-9),61.3(c-10),99.7(c-1’),74.8(c-2’),78.7(c-3’),71.8(c-4’),77.7(c-5’),62.9(c-6’),122.0(c-1”),116.0(c-2”),146.3(c-3”),152.2(c-4”),117.5(c-5”),123.9(c-6”),168.0(c-7”).
上述数据分析结果与文献(archivesofpharmacalresearch,2009,32(2):207-213)中报道的verproside一致。
实施例3梓苷经结构修饰获得梓醇衍生物的制备
在反应瓶中加入梓苷24mg(0.05mmol)和3mln,n-二甲基甲酰胺(dmf)，室温搅拌下加入r1x(0.10mmol)(表1)和无水k2co3(21mg,0.15mmol)，于30℃反应至终点(tlc跟踪)。加入适量100-200目硅胶拌样，减压回收溶剂至呈流沙状，经硅胶和mci柱层析分离得到相应的式iii类化合物，收率在50％-98％之间。
表1制备新梓醇衍生物的底物试剂
iii-1：1hnmr(600mhz,c5d5n)：δh5.53(1h,d,j＝9.1hz,h-1),6.43(1h,dd,j＝1.4/5.9hz,h-3),5.06(1h,dd,j＝5.9/4.1hz,h-4),2.91(1h,m,h-5),5.28(1h,brd,j＝7.6hz,h-6),3.97(1h,brs,h-7),2.88(1h,m,h-9),4.50(1h,d,j＝13.3hz,h-10a),4.42(1h,d,j＝13.3hz,h-10b),5.51(1h,d,j＝7.9hz,h-1′),4.13(1h,dd,j＝7.9/8.9hz,h-2′),4.28(1h,t,j＝8.9hz,h-3′),4.21(1h,t,j＝8.9hz,h-4′),3.99(1h,m,h-5′),4.32(1h,dd,j＝11.9/5.5hz,h-6′a),4.50(1h,m,h-6′b),8.13(2h,d,j＝8.9hz,h-2″,6″),7.19(2h,d,j＝8.9hz,h-3″,5″),8.11(2h,d,j＝7.9hz,h-2″′,6″′),7.43(2h,t,j＝7.9hz,h-3″′,5″′),7.54(1h,m,h-4″′),5.74(2h,s,h-8″′).13cnmr(150mhz,c5d5n):δc95.0(c-1),141.9(c-3),102.7(c-4),36.7(c-5),81.3(c-6),59.7(c-7),67.4(c-8),43.5(c-9),60.4(c-l0),100.5(c-l′),75.4(c-2′),79.4(c-3′),71.8(c-4′),78.7(c-5′),62.9(c-6′),123.5(c-1″),132.6(c-2″,6″),115.4(c-3″,5″),163.2(c-4″),166.5(c-7″),135.4(c-1″′),129.6(c-2″′,6″′),128.7(c-3″′,5″′),134.5(c-4″′),194.3(c-7″′),71.3(c-8″′).hresims:calcdforc30h32nao13[m+na]+623.1735,found:623.1752.
iii-2：1hnmr(600mhz,cd3od)：δh5.20(1h,d,j＝9.2hz,h-1),6.38(1h,dd,j＝1.2/6.0hz,h-3),5.00(1h,dd,j＝6.0/4.2hz,h-4),2.68(1h,m,h-5),5.14(1h,brd,j＝7.2hz,h-6),3.77(1h,brs,h-7),2.65(1h,m,h-9),4.18(1h,d,j＝13.2hz,h-10a),3.86(1h,d,j＝13.2hz,h-10b),4.81(1h,d,j＝7.9hz,h-1′),3.28(2h,m,h-2′,4′),3.42(1h,t,j＝9.1hz,h-3′),3.34(1h,m,h-5′),3.66(1h,dd,j＝6.7/12.0hz,h-6′a),3.90(1h,dd,j＝12.0/1.7hz,h-6′b),8.04(2h,d,j＝8.9hz,h-2″,6″),7.09(2h,d,j＝8.9hz,h-3″,5″),4.60(2h,s,h-2″′).13cnmr(150mhz,cd3od):δc95.2(c-1),142.6(c-3),103.0(c-4),36.9(c-5),82.0(c-6),60.4(c-7),67.1(c-8),43.3(c-9),61.4(c-l0),99.8(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),124.3(c-1″),133.0(c-2″,6″),115.9(c-3″,5″),163.4(c-4″),167.6(c-7″),173.4(c-l″′),68.0(c-2″′)。hresims:calcdforc24h29nnao13[m+na]+562.1531,found:562.1542.
iii-3：1hnmr(600mhz,cd3od)：δh5.20(1h,d,j＝9.4hz,h-1),6.39(1h,dd,j＝6.0/1.7hz,h-3),5.01(1h,dd,j＝6.0/4.3hz,h-4),2.69(1h,m,h-5),5.15(1h,dd,j＝8.0/1.0hz,h-6),3.77(1h,d,j＝1.0hz,h-7),2.66(1h,m,h-9),4.19(1h,d,j＝13.2hz,h-10a),3.86(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.9hz,h-1′),3.27(2h,m,h-2′,4′),3.42(1h,t,j＝9.0hz,h-3′),3.33(1h,m,h-5′),3.65(1h,dd,j＝12.0/6.7hz,h-6′a),3.94(1h,dd,j＝12.0/2.0hz,h-6′b),8.07(2h,d,j＝9.0hz,h-2″,6″),7.18(2h,d,j＝9.0hz,h-3″,5″),7.10(3h,m,h-3″′,4″′,5″′),4.85(2h,s,h-8″′),2.18(6h,ch3×2).13cnmr(150mhz,cd3od):δc95.2(c-1),142.6(c-3),103.0(c-4),36.9(c-5),82.0(c-6),60.4(c-7),67.1(c-8),43.3(c-9),61.4(c-l0),99.8(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),124.5(c-1″),133.0(c-2″,6″),116.0(c-3″,5″),163.5(c-4″),167.6(c-7″),134.8(c-l″′),137.2(c-2″′,6″′),129.3(c-3″′,5″′),128.8(c-4″′),169.6(c-7″′),68.4(c-8″′),18.5(ch3×2)。hresims:calcdforc32h37nnao13[m+na]+666.2157,found:666.2162.
iii-4：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.6hz,h-1),6.43(1h,dd,j＝1.7/5.9hz,h-3),4.97(1h,dd,j＝5.9/4.5hz,h-4),2.58(1h,m,h-5),5.09(1h,dd,j＝8.1/1.0hz,h-6),3.69(1h,brs,h-7),2.46(1h,dd,j＝9.6/7.9hz,h-9),3.92(1h,dd,j＝13.2/4.5hz,h-10a),3.74(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.17(2h,m,h-3′,5′),3.43(1h,m,h-6′b),7.95(2h,d,j＝8.9hz,h-2″,6″),7.12(2h,d,j＝8.9hz,h-3″,5″),8.12(2h,dd,j＝8.9/5.5hz,h-2″′,6″′),7.43(2h,t,j＝8.9hz,h-3″′,5″′),5.72(2h,s,h-8″′),4.35(1h,m,10-oh),4.57(1h,brs,6′-oh).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.8(c-1″),131.4(c-2″,6″),114.8(c-3″,5″),162.1(c-4″),165.3(c-7″),166.4(c-1″′),131.4(c-2″′or6″′),131.1(c-2″′or6″′),116.1(c-3″′or5″′),115.9(c-3″′or5″′),164.4(c-4″′),192.6(c-7″′),70.2(c-8″′).hresims:calcdforc30h31fnao13[m+na]+641.1641,found:641.1654.
iii-5：1hnmr(600mhz,cd3od)：δh5.20(1h,d,j＝9.0hz,h-1),6.38(1h,brd,j＝6.0hz,h-3),5.00(1h,dd,j＝6.0/4.6hz,h-4),2.68(1h,m,h-5),5.14(1h,brd,j＝7.6hz,h-6),3.76(1h,brs,h-7),2.65(1h,m,h-9),4.18(1h,d,j＝13.2hz,h-10a),3.86(1h,d,j＝13.2hz,h-10b),4.81(1h,d,j＝7.9hz,h-1′),3.28(2h,m,h-2′,4′),3.43(5h,m,h-3′,ch2,ch2′),3.34(1h,m,h-5′),3.65(1h,dd,j＝11.9/6.6hz,h-6′a),3.94(1h,brd,j＝11.9hz,h-6′b),8.02(2h,d,j＝8.5hz,h-2″,6″),7.04(2h,d,j＝8.5hz,h-3″,5″),4.89(2h,s,h-2″′),1.26(3h,t,j＝7.0hz,ch3),1.15(3h,t,j＝7.1hz,ch3′).13cnmr(150mhz,cd3od):δc95.2(c-1),142.6(c-3),103.0(c-4),36.9(c-5),82.0(c-6),60.4(c-7),67.0(c-8),43.3(c-9),61.4(c-l0),99.8(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),124.0(c-1″),132.9(c-2″,6″),115.8(c-3″,5″),164.0(c-4″),169.0(c-l″′),67.5(c-2″′),42.7(ch2),41.8(ch2′),14.5(ch3),13.2(ch3′)。hresims:calcdforc28h36no13[m-h]-594.2192,found:594.2179.
iii-6：1hnmr(500mhz,dmso-d6)：δh5.12(1h,d,j＝9.6hz,h-1),6.43(1h,dd,j＝1.7/5.9hz,h-3),4.98(1h,dd,j＝5.9/4.5hz,h-4),2.58(1h,m,h-5),5.09(1h,dd,j＝8.1/1.1hz,h-6),3.72(1h,brs,h-7),2.48(1h,m,h-9),3.93(1h,dd,j＝13.3/4.8hz,h-10a),3.72(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.05(2h,m,h-2′,4′),3.17(2h,m,h-3′,5′),3.43(1h,m,h-6′b),7.98(2h,d,j＝9.0hz,h-2″,6″),7.15(2h,d,j＝9.0hz,h-3″,5″),5.50(2h,s,ar-o-ch2-),7.86(1h,d,j＝8.3hz,h-3″′),7.72(1h,dd,j＝8.3/2.0hz,h-4″′),7.86(1h,d,j＝2.0hz,h-6″′),3.81(3h,s,och3).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.2(c-3),101.8(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.5(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),122.0(c-1″),131.7(c-2″,6″),114.9(c-3″,5″),162.1(c-4″),165.3(c-7″),67.2(ar-ch2-o-),140.0(c-1″′),127.7(c-2″′),132.4(c-3″′),130.8(c-4″′),126.4(c-5″′),131.1(c-6″′),166.1(c-7″′),52.4(och3″′).hresims:calcdforc31h33brclo14[m+cl]-743.0748,found:743.0761.
iii-7：1hnmr(500mhz,dmso-d6)：δh5.12(1h,d,j＝9.6hz,h-1),6.43(1h,dd,j＝1.7/5.9hz,h-3),4.97(1h,dd,j＝5.9/4.5hz,h-4),2.58(1h,m,h-5),5.09(1h,dd,j＝8.1/1.0hz,h-6),3.72(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,brd,j＝12.7hz,h-10a),3.74(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.43(1h,m,h-6′b),7.96(2h,d,j＝9.0hz,h-2″,6″),7.14(2h,d,j＝9.0hz,h-3″,5″),5.76(2h,s,ar-o-ch2-),8.12(2h,d,j＝8.4hz,h-2″′,6″′),7.89(2h,d,j＝8.4hz,h-3″′,5″′),7.78(2h,brd,j＝7.3hz,h-2″″,6″″),7.52(2h,brt,j＝7.3hz,h-3″″,5″″),7.45(1h,brt,j＝7.3hz,h-4″″).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.8(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.8(c-1″),131.4(c-2″,6″),114.8(c-3″,5″),162.2(c-4″),165.3(c-7″),70.3(ar-o-ch2-),133.0(c-1″′),129.2(c-2″′,6″′),127.0(c-3″′,5″′),145.3(c-6″′),193.5(c-7″′),138.8(c-1″″),127.1(c-2″″,6″″),128.7(c-3″″,5″″),128.6(c-6″″).hresims:calcdforc36h35o13[m-h]-675.2083,found:675.2088.
iii-8：1hnmr(500mhz,cd3od)：δh5.20(1h,d,j＝9.2hz,h-1),6.38(1h,dd,j＝1.4/6.0hz,h-3),5.00(1h,dd,j＝6.0/4.1hz,h-4),2.69(1h,m,h-5),5.13(1h,dd,j＝7.8/1.0hz,h-6),3.75(1h,brs,h-7),2.67(1h,m,h-9),4.18(1h,d,j＝13.2hz,h-10a),3.85(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.9hz,h-1′),3.27(2h,m,h-2′,4′),3.41(1h,t,j＝9.1hz,h-3′),3.34(1h,m,h-5′),3.65(1h,dd,j＝6.7/12.0hz,h-6′a),3.94(1h,dd,j＝12.0/2.1hz,h-6′b),7.98(2h,brd,j＝9.0hz,h-2″,6″),6.96(2h,brd,j＝9.0hz,h-3″,5″),4.90(1h,m,h-1″′),2.00(2h,m,h-2″′,5″′),1.80(4h,m,h-2″′,3″′,4″′,5″′),1.67(2h,m,h-3″′,4″′).13cnmr(125mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),81.8(c-6),60.4(c-7),67.0(c-8),43.4(c-9),61.5(c-l0),99.9(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.9(c-5′),63.1(c-6′),122.7(c-1″),132.9(c-2″,6″),116.4(c-3″,5″),164.1(c-4″),167.9(c-7″),81.1(c-l″′),33.9(c-2″′,5″′),25.1(c-3″′,4″′)。hresims:calcdforc27h33o12[m-h]+549.1978,found:549.1975.
iii-9：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.8hz,h-1),6.43(1h,dd,j＝5.9/1.4hz,h-3),4.98(1h,dd,j＝5.9/4.9hz,h-4),2.58(1h,m,h-5),5.08(1h,d,j＝8.1hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,dd,j＝13.2/5.0hz,h-10a),3.72(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.05(2h,m,h-2′,4′),3.17(2h,m,h-3′,5′),3.43(1h,m,h-6′b),7.96(2h,d,j＝8.8hz,h-2″,6″),7.14(2h,d,j＝8.8hz,h-3″,5″),5.16(2h,s,-ch2-o-),7.28(2h,d,j＝8.2hz,h-2″′,6″′),7.41(2h,d,j＝8.2hz,h-3″′,5″′),2.47(3h,s,sch3).13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.8(c-6),58.2(c-7),65.8(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.6(c-1″),131.5(c-2″,6″),115.0(c-3″,5″),162.4(c-4″),165.3(c-7″),69.2(-ch2-o-),132.9(c-1″′),125.9(c-2″′,6″′),128.6(c-3″′,5″′),138.1(c-4″′),14.6(sch3″′).hresims:calcdforc30h33o12s[m-h]-617.1698,found:617.1684.
iii-10：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.8hz,h-1),6.42(1h,dd,j＝5.9/1.8hz,h-3),4.97(1h,dd,j＝5.9/4.5hz,h-4),2.58(1h,m,h-5),5.08(1h,dd,j＝8.1/1.0hz,h-6),3.71(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,brd,j＝13.2hz,h-10a),3.73(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.05(2h,m,h-2′,4′),3.17(2h,m,h-3′,5′),3.43(1h,m,h-6′b),7.97(2h,brd,j＝8.9hz,h-2″,6″),7.16(2h,d,j＝8.9hz,h-3″,5″),5.23(2h,s,-ch2-o-),7.75(1h,d,j＝1.9hz,h-2″′),7.67(1h,d,j＝8.3hz,h-5″′),7.47(1h,dd,j＝8.3/1.9hz,h-6″′).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.9(c-1″),131.6(c-2″,6″),115.0(c-3″,5″),162.1(c-4″),165.3(c-7″),67.9(-ch2-o-),137.7(c-1″′),129.6(c-2″′),130.6(c-3″′),131.2(c-4″′),130.8(c-5″′),128.0(c-6″′).hresims:calcdforc29h30cl2nao12[m+na]+663.1007,found:663.1010.
iii-11：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.6hz,h-1),6.42(1h,dd,j＝5.9/1.7hz,h-3),4.97(1h,dd,j＝5.9/4.5hz,h-4),2.58(1h,m,h-5),5.08(1h,dd,j＝8.1/1.1hz,h-6),3.71(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,dd,j＝13.3/5.1hz,h-10a),3.72(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.05(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.43(1h,m,h-6′b),7.97(2h,brd,j＝8.9hz,h-2″,6″),7.16(2h,brd,j＝8.9hz,h-3″,5″),5.33(2h,s,-ch2-o-),7.66(2h,brd,j＝8.3hz,h-2″′,6″′),7.87(2h,d,j＝8.3hz,h-3″′,5″′).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.2(c-3),101.8(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.5(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),122.0(c-1″),131.6(c-2″,6″),115.0(c-3″,5″),162.1(c-4″),165.3(c-7″),68.6(-ch2-o-),142.2(c-1″′),128.2(c-2″′,6″′),132.5(c-3″′,5″′),110.7(c-4″′),118.7(cn″′).hresims:calcdforc30h31nnao12[m+na]+620.1738,found:620.1741.
iii-12：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.6hz,h-1),6.42(1h,dd,j＝5.9/1.7hz,h-3),4.96(1h,dd,j＝5.9/4.6hz,h-4),2.58(1h,m,h-5),5.08(1h,brd,j＝8.2hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,dd,j＝13.3/5.1hz,h-10a),3.72(2h,m,h-10b,6′a),4.62(1h,d,j＝7.8hz,h-1′),3.05(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.42(1h,m,h-6′b),7.97(2h,brd,j＝8.9hz,h-2″,6″),7.22(2h,brd,j＝8.9hz,h-3″,5″),5.48(2h,s,-ch2-o-),7.68(1h,d,j＝8.5hz,h-3″′),8.43(1h,d,j＝8.5hz,h-4″′),8.00(1h,brd,j＝8.5hz,h-6″′),7.63(1h,brt,j＝8.5hz,h-7″′),7.80(1h,brt,j＝8.5hz,h-8″′),8.03(1h,brd,j＝8.5hz,h-9″′).13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.8(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.9(c-1″),131.6(c-2″,6″),115.0(c-3″,5″),162.3(c-4″),165.3(c-7″),71.0(-ch2-o-),156.9(c-2″′),119.6(c-3″′),137.2(c-4″′),127.2(c-5″′),128.0(c-6″′),126.7(c-7″′),130.0(c-8″′),128.6(c-9″′),147.0(c-10″′).hresims:calcdforc32h34no12[m+h]+624.2076,found:624.2066.
iii-13：1hnmr(500mhz,dmso-d6)：δh5.10(1h,d,j＝9.6hz,h-1),6.42(1h,dd,j＝5.9/1.7hz,h-3),4.97(1h,dd,j＝5.9/4.6hz,h-4),2.58(1h,m,h-5),5.08(1h,dd,j＝8.2/1.0hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,dd,j＝13.3/5.2hz,h-10a),3.72(2h,m,h-10b,6′a),4.62(1h,d,j＝7.8hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.42(1h,m,h-6′b),7.96(2h,brd,j＝8.9hz,h-2″,6″),7.14(2h,brd,j＝8.9hz,h-3″,5″),5.18(2h,s,-ch2-o-),7.27(2h,brd,j＝8.3hz,h-2″′,6″′),7.76(2h,brd,j＝8.3hz,h-3″′,5″′).13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.8(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.7(c-1″),131.5(c-2″,6″),115.0(c-3″,5″),162.3(c-4″),165.3(c-7″),68.8(-ch2-o-),136.3(c-1″′),130.0(c-2″′,6″′),137.3(c-3″′,5″′),94.2(c-4″′).hresims:calcdforc29h31inao12[m+na]+721.0752,found:721.0771.
iii-14：1hnmr(500mhz,dmso-d6)：δh5.13(1h,d,j＝9.9hz,h-1),6.45(1h,brd,j＝5.8hz,h-3),4.99(1h,brt,j＝5.2hz,h-4),2.61(1h,m,h-5),5.11(1h,brd,j＝8.3hz,h-6),3.74(1h,brs,h-7),3.94(1h,dd,j＝13.2/5.1hz,h-10a),3.74(2h,m,h-10b,6′a),4.63(1h,d,j＝7.8hz,h-1′),3.05(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.44(1h,m,h-6′b),8.03(2h,brd,j＝8.7hz,h-2″,6″),7.33(2h,brd,j＝8.7hz,h-3″,5″),6.17(2h,s,-ch2-o-),8.35(2h,d,j＝8.8hz,h-1″′,8″′),7.59(4h,m,h-2″′,3″′,6″′,7″′),8.17(2h,d,j＝8.3hz,h-4″′,5″′),8.74(1h,s,h-10″′).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.2(c-3),101.8(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.8(c-1″),131.5(c-2″,6″),115.0(c-3″,5″),163.0(c-4″),165.4(c-7″),62.7(-ch2-o-),126.8(c-1″′,8″′),125.3(c-2″′,7″′),124.1(c-3″′,6″′),129.0(c-4″′,5″′),126.7(c-9″′),128.9(c-10″′),130.5(c-4a″′,10a″′),131.0(c-8a″′,9a″′).hresims:calcdforc37h36nao12[m+na]+695.2099,found:695.2112.
iii-15：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.7hz,h-1),6.42(1h,dd,j＝5.9/1.7hz,h-3),4.97(1h,dd,j＝5.9/4.6hz,h-4),2.57(1h,m,h-5),5.07(1h,dd,j＝8.1/0.9hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,dd,j＝13.3/5.1hz,h-10a),3.72(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.43(1h,m,h-6′b),7.95(2h,brd,j＝8.8hz,h-2″,6″),7.14(2h,brd,j＝8.8hz,h-3″,5″),5.15(2h,s,-ch2-o-),7.21(2h,brd,j＝8.0hz,h-2″′,6″′),7.36(2h,brd,j＝8.0hz,h-3″′,5″′),2.57(2h,t,j＝7.6hz,h-7″),1.54(2h,quint,j＝7.6hz,h-8″),1.29(2h,sext,j＝7.6hz,h-9″),0.89(3h,t,j＝7.6hz,h-10″).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.5(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.6(c-1″),131.5(c-2″,6″),114.9(c-3″,5″),162.6(c-4″),165.4(c-7″),69.5(-ch2-o-),133.6(c-1″′),128.0(c-2″′,6″′),128.4(c-3″′,5″′),142.3(c-4″′),34.6(c-7″′),33.1(c-8″′),21.7(c-9″′),13.8(c-10″′).hresims:calcdforc33h39o12[m-h]-627.2447,found:627.2458.
iii-16：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.2hz,h-1),6.43(1h,dd,j＝5.9/1.5hz,h-3),4.97(1h,dd,j＝5.9/4.8hz,h-4),2.58(1h,m,h-5),5.08(1h,brd,j＝8.1hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,dd,j＝13.2/5.1hz,h-10a),3.73(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.42(1h,m,h-6′b),7.96(2h,brd,j＝8.9hz,h-2″,6″),7.14(2h,brd,j＝8.9hz,h-3″,5″),5.14(2h,s,-ch2-o-),6.62(2h,d,j＝2.2hz,h-2″′,6″′),6.46(1h,t,j＝2.2hz,h-4″′),3.74(6h,s,och3″′×2).13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.8(c-6),58.2(c-7),65.8(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.6(c-1″),131.5(c-2″,6″),114.9(c-3″,5″),162.4(c-4″),165.3(c-7″),69.4(-ch2-o-),138.7(c-1″′),105.5(c-2″′,6″′),160.6(c-3″′,5″′),92.9(c-4″′),55.2(och3″′×2).hresims:calcdforc31h35o14[m-h]-631.2032,found:631.2045.
iii-17：1hnmr(500mhz,dmso-d6+d2o)：δh5.10(1h,d,j＝9.6hz,h-1),6.41(1h,dd,j＝5.9/1.7hz,h-3),4.95(1h,dd,j＝5.9/4.6hz,h-4),2.56(1h,m,h-5),5.07(1h,dd,j＝8.0/1.0hz,h-6),3.69(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,d,j＝13.3hz,h-10a),3.71(2h,m,h-10b,6′a),4.61(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.17(2h,m,h-3′,5′),3.42(1h,dd,j＝11.9/6.8hz,h-6′b),7.96(2h,brd,j＝8.9hz,h-2″,6″),7.17(2h,brd,j＝8.9hz,h-3″,5″),5.36(2h,s,-ch2-o-),7.72(2h,d,j＝8.8hz,h-2″′,6″′),8.25(1h,brd,j＝8.8hz,h-3″′,5″′).13cnmr(125mhz,dmso-d6+d2o):δc93.2(c-1),141.4(c-3),102.0(c-4),35.4(c-5),80.1(c-6),58.5(c-7),66.1(c-8),41.9(c-9),58.7(c-l0),98.1(c-l′),73.5(c-2′),77.5(c-3′),70.3(c-4′),76.3(c-5′),61.4(c-6′),122.2(c-1″),131.8(c-2″,6″),115.2(c-3″,5″),162.2(c-4″),165.6(c-7″),68.5(-ch2-o-),141.4(c-1″′),128.6(c-2″′,6″′),123.9(c-3″′,5″′),147.3(c-4″′).hresims:calcdforc29h30no14[m-h]-616.1672,found:616.1682.
iii-18：1hnmr(500mhz,dmso-d6+d2o)：δh5.10(1h,d,j＝9.6hz,h-1),6.41(1h,dd,j＝5.9/1.5hz,h-3),4.96(1h,dd,j＝5.9/4.8hz,h-4),2.57(1h,m,h-5),5.08(1h,brd,j＝8.3hz,h-6),3.70(1h,brs,h-7),2.47(1h,m,h-9),3.93(1h,d,j＝13.2hz,h-10a),3.71(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.19(2h,m,h-3′,5′),3.42(1h,dd,j＝11.9/6.7hz,h-6′b),7.97(2h,brd,j＝8.9hz,h-2″,6″),7.23(2h,brd,j＝8.9hz,h-3″,5″),5.64(2h,s,-ch2-o-),7.68(1h,brd,j＝7.5hz,h-2″′),7.51(1h,brt,j＝7.5hz,h-3″′),8.06(1h,brd,j＝7.5hz,h-4″′),7.94(1h,brd,j＝8.3hz,h-5″′),7.58(2h,m,h-6″′,7″′),7.97(1h,brd,j＝8.3hz,h-2″′).13cnmr(125mhz,dmso-d6+d2o):δc93.2(c-1),141.4(c-3),102.0(c-4),35.4(c-5),80.1(c-6),58.5(c-7),66.1(c-8),41.9(c-9),58.7(c-l0),98.1(c-l′),73.5(c-2′),77.5(c-3′),70.3(c-4′),76.3(c-5′),61.4(c-6′),121.9(c-1″),131.8(c-2″,6″),115.3(c-3″,5″),162.8(c-4″),165.7(c-7″),68.4(-ch2-o-),131.3(c-1″′),127.3(c-2″′),125.7(c-3″′),128.8(c-4″′),133.6(c-4a″′),129.2(c-5″′),126.9(c-6″′),126.4(c-7″′),124.0(c-8″′),132.0(c-8a″′).hresims:calcdforc33h33o12[m-h]-621.1978,found:621.1982.
iii-19：1hnmr(500mhz,dmso-d6+d2o)：δh5.10(1h,d,j＝9.5hz,h-1),6.41(1h,dd,j＝5.9/1.7hz,h-3),4.96(1h,dd,j＝5.9/4.5hz,h-4),2.56(1h,m,h-5),5.07(1h,dd,j＝8.1/1.0hz,h-6),3.70(1h,brs,h-7),2.48(1h,m,h-9),3.93(1h,d,j＝13.3hz,h-10a),3.71(2h,m,h-10b,6′a),4.61(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.42(1h,dd,j＝11.9/6.8hz,,h-6′b),7.97(2h,brd,j＝8.9hz,h-2″,6″),7.18(2h,brd,j＝8.9hz,h-3″,5″),5.24(2h,s,-o-ch2-),7.30(2h,d,j＝8.2hz,h-2″′,6″′),7.50(2h,d,j＝8.2hz,h-3″′,5″′),7.43(1h,dd,j＝7.7/1.1hz,h-3″″),7.61(1h,td,j＝7.7/1.1hz,h-4″″),7.48(1h,td,j＝7.7/1.1hz,h-5″″),7.73(1h,dd,j＝7.7/1.1hz,h-6″″).13cnmr(125mhz,dmso-d6+d2o):δc93.3(c-1),141.4(c-3),102.0(c-4),35.4(c-5),80.1(c-6),58.5(c-7),66.1(c-8),42.0(c-9),58.7(c-l0),98.1(c-l′),73.5(c-2′),77.6(c-3′),70.3(c-4′),76.4(c-5′),61.5(c-6′),121.9(c-1″),131.8(c-2″,6″),115.3(c-3″,5″),162.8(c-4″),165.7(c-7″),69.6(-o-ch2-),140.5(c-1″′),128.1(c-2″′,6″′),128.6(c-3″′,5″′),141.1(c-4″′),135.7(c-1″″),131.0(c-2″″),130.8(c-3″″),129.6(c-4″″),131.9(c-5″″),127.9(c-6″″),168.8(c-7″″),52.3(och3″″).hresims:calcdforc37h38nao14[m+na]+729.2154,found:729.2154.
iii-20：1hnmr(500mhz,dmso-d6+d2o)：δh5.09(1h,d,j＝9.6hz,h-1),6.41(1h,dd,j＝5.9/1.5hz,h-3),4.95(1h,dd,j＝5.9/4.6hz,h-4),2.55(1h,m,h-5),5.07(1h,d,j＝8.1hz,h-6),3.69(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,d,j＝13.3hz,h-10a),3.71(2h,m,h-10b,6′a),4.61(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.17(2h,m,h-3′,5′),3.42(1h,dd,j＝12.0/6.8hz,h-6′b),7.96(2h,d,j＝8.9hz,h-2″,6″),7.16(2h,d,j＝8.9hz,h-3″,5″),5.33(2h,s,-ch2-o-),7.72(2h,d,j＝8.3hz,h-2″′,6″′),7.94(2h,d,j＝8.3hz,h-3″′,5″′),3.19(3h,s,so2ch3).13cnmr(125mhz,dmso-d6+d2o):δc93.2(c-1),141.4(c-3),102.0(c-4),35.4(c-5),80.1(c-6),58.5(c-7),66.1(c-8),41.9(c-9),58.7(c-l0),98.1(c-l′),73.5(c-2′),77.5(c-3′),70.3(c-4′),76.3(c-5′),61.4(c-6′),122.1(c-1″),131.9(c-2″,6″),115.3(c-3″,5″),162.4(c-4″),165.6(c-7″),68.8(-ch2-o-),142.7(c-1″′),127.5(c-2″′,6″′),128.5(c-3″′,5″′),140.4(c-4″′),43.8(so2ch3″′).hresims:calcdforc30h34nao14s[m+na]+673.1561,found:673.1556.
iii-21：1hnmr(500mhz,dmso-d6)：δh5.13(1h,d,j＝9.7hz,h-1),6.44(1h,dd,j＝5.9/1.7hz,h-3),4.98(1h,dd,j＝5.9/4.8hz,h-4),2.60(1h,m,h-5),5.10(1h,m,h-6),3.73(1h,brs,h-7),3.93(1h,dd,j＝13.3/5.3hz,h-10a),3.75(2h,m,h-10b,6′a),4.63(1h,d,j＝7.8hz,h-1′),3.05(2h,m,h-2′,4′),3.19(2h,m,h-3′,5′),3.44(1h,m,h-6′b),8.02(2h,brd,j＝8.8hz,h-2″,6″),7.32(2h,brd,j＝8.8hz,h-3″,5″),6.24(2h,s,-ch2-o-),8.46(2h,d,j＝8.8hz,h-1″′,8″′),7.70(2h,td,j＝8.8/1.0hz,h-2″′,7″′),7.89(2h,td,j＝8.8/1.0hz,h-3″′,6″′),8.02(2h,d,j＝8.8hz,h-4″′,5″′).13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),122.1(c-1″),131.5(c-2″,6″),115.1(c-3″,5″),162.5(c-4″),165.3(c-7″),61.8(-ch2-o-),126.8(c-1″′,8″′),124.6(c-2″′,7″′),130.3(c-3″′,6″′),129.8(c-4″′,5″′),148.0(c-9″′),137.8(c-4a″′,10a″′),124.9(c-8a″′,9a″′).hresims:calcdforc36h36no12[m+h]+674.2232,found:674.2236.
iii-22：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.7hz,h-1),6.42(1h,dd,j＝5.9/1.7hz,h-3),4.97(1h,dd,j＝5.9/4.5hz,h-4),2.58(1h,m,h-5),5.08(1h,dd,j＝8.1/1.0hz,h-6),3.71(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,dd,j＝13.3/5.1hz,h-10a),3.73(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.05(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.43(1h,m,h-6′b),7.97(2h,brd,j＝8.8hz,h-2″,6″),7.18(2h,brd,j＝8.8hz,h-3″,5″),5.25(2h,s,-ch2-o-),7.87(2h,brd,j＝8.6hz,h-2″′,6″′),7.59(2h,brd,j＝8.6hz,h-3″′,5″′),7.75(1h,d,j＝1.7hz,h-3″″),6.55(1h,dd,j＝1.7/1.5hz,h-4″″),8.50(1h,d,j＝1.5hz,h-5″″).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.1(c-3),101.7(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.5(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.7(c-1″),131.5(c-2″,6″),115.0(c-3″,5″),162.6(c-4″),165.4(c-7″),69.0(-ch2-o-),139.4(c-1″′),129.1(c-2″′,6″′),118.4(c-3″′,5″′),134.2(c-4″′),141.1(c-3″″),107.9(c-4″″),127.8(c-5″″).hresims:calcdforc32h35n2o12[m+h]+639.2185,found:639.2177.
iii-23：1hnmr(400mhz,dmso-d6)：δh5.09(1h,d,j＝9.8hz,h-1),6.40(1h,brd,j＝5.8hz,h-3),4.97(1h,brt,j＝5.3hz,h-4),2.55(1h,m,h-5),5.06(1h,m,h-6),3.67(1h,brs,h-7),2.46(1h,m,h-9),3.91(1h,dd,j＝13.3/5.1hz,h-10a),3.72(2h,m,h-10b,6′a),4.60(1h,d,j＝7.7hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),7.89(2h,brd,j＝8.8hz,h-2″,6″),7.16(2h,brd,j＝8.8hz,h-3″,5″),6.68(1h,s,-ch-o-),7.50(4h,d,j＝7.5hz,h-c-2″′,6″′,c-2″″,6″″),7.35(4h,t,j＝7.5hz,h-c-3″′,5″′,c-3″″,5″″),7.27(2h,s,t,j＝7.5hz,h-4″″,4″″).13cnmr(100mhz,dmso-d6):δc93.1(c-1),141.2(c-3),101.8(c-4),35.2(c-5),79.9(c-6),58.3(c-7),65.9(c-8),41.8(c-9),58.6(c-l0),98.0(c-l′),73.5(c-2′),77.5(c-3′),70.3(c-4′),76.5(c-5′),61.5(c-6′),121.8(c-1″),131.5(c-2″,6″),116.2(c-3″,5″),161.5(c-4″),165.4(c-7″),80.1(-ch-o-),141.0(c-1″′,1″″),126.6(c-2″′,6″′,2″″,6″″),128.8(c-3″′,5″′,c-3″″,5″″),127.9(c-4″″,4″″).hresims:calcdforc35h36nao12[m+na]+671.2099,found:671.2106.
实施例4胡黄连苷ii经结构修饰获得梓醇衍生物的制备
在反应瓶中加入胡黄连25mg(0.05mmol)和3mln,n-二甲基甲酰胺(dmf)，室温搅拌下加入r1x(0.10mmol)(表1)和无水k2co3(21mg,0.15mmol)，于30℃反应至终点(tlc跟踪)。加入适量100-200目硅胶拌样，减压回收溶剂至呈流沙状，经硅胶和mci柱层析分离得到相应的式iv类化合物，收率在50％-98％之间。
iv-1：1hnmr(500mhz,dmso-d6)：δh5.10(1h,d,j＝9.6hz,h-1),6.41(1h,dd,j＝5.9/1.7hz,h-3),4.96(1h,dd,j＝5.8/4.5hz,h-4),2.58(1h,m,h-5),5.07(1h,dd,j＝8.1/1.0hz,h-6),3.71(1h,brs,h-7),2.47(1h,dd,j＝9.6/7.9hz,h-9),3.90(1h,dd,j＝13.3/4.9hz,h-10a),3.73(2h,m,h-10b,6′a),4.61(1h,d,j＝7.9hz,h-1′),3.02(2h,m,h-2′,4′),3.16(2h,m,h-3′,5′),3.41(1h,m,h-6′b),7.50(1h,d,j＝2.0hz,h-2″),7.02(1h,d,j＝8.6hz,h-5″),7.54(1h,dd,j＝8.6/2.0hz,h-6″),3.85(3h,s,och3),8.01(2h,dd,j＝8.0/1.2hz,h-2″′,6″′),7.58(2h,t,j＝8.0hz,h-3″′,5″′),7.54(1h,dt,j＝8.0/1.2hz,h-4″′),5.72(2h,s,h-8″′),4.32(1h,dd,,j＝7.3/5.4hz,10-oh),4.55(1h,dd,,j＝7.5/4.8hz,10-oh),.13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.8(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.8(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.8(c-1″),112.3(c-2″),151.9(c-3″),148.5(c-4″),112.6(c-5″),123.2(c-6″),165.4(c-7″),55.7(och3),134.2(c-1″′),128.9(c-2″′,6″′),127.9(c-3″′,5″′),133.9(c-4″′),193.9(c-7″′),70.5(c-8″′).hresims:calcdforc31h33o14[m-h]-629.1876,found:629.1875.
iv-2：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.6hz,h-1),6.42(1h,brd,j＝5.8hz,h-3),4.97(1h,brt,j＝5.1hz,h-4),2.59(1h,m,h-5),5.09(1h,brd,j＝8.1hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.90(1h,dd,j＝13.3/4.9hz,h-10a),3.74(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.42(1h,m,h-6′b),7.50(1h,d,j＝1.4hz,h-2″),7.00(1h,d,j＝8.5hz,h-5″),7.60(1h,dd,j＝8.5/1.4hz,h-6″),3.85(3h,s,och3),4.55(2h,s,h-2″′),7.41(1h,s,n-h),7.39(1h,s,n-h′),4.36(1h,dd,,j＝7.3/5.4hz,10-oh),4.58(1h,dd,,j＝7.4/4.7hz,10-oh),13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.2(c-3),101.8(c-4),35.2(c-5),80.0(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.5(c-l0),97.9(c-l′),73.5(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.5(c-6′),122.2(c-1″),112.3(c-2″),151.8(c-3″),148.8(c-4″),112.9(c-5″),123.3(c-6″),165.5(c-7″),55.8(och3),169.4(c-l″′),67.3(c-2″′)。hresims:calcdforc25h30no14[m-h]-568.1672,found:568.1667.
iv-3：1hnmr(500mhz,dmso-d6)：δh5.12(1h,d,j＝9.6hz,h-1),6.42(1h,dd,j＝5.9/1.8hz,h-3),4.97(1h,dd,j＝5.9/4.5hz,h-4),2.59(1h,m,h-5),5.09(1h,dd,j＝8.1/1.0hz,h-6),3.71(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,dd,j＝13.2/4.7hz,h-10a),3.73(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.05(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),7.52(1h,m,h-2″),7.05(1h,d,j＝8.6hz,h-5″),7.57(1h,dd,j＝8.6/2.0hz,h-6″),3.87(3h,s,och3),5.75(2h,s,ar-o-ch2-),8.11(2h,d,j＝8.5hz,h-2″′,6″′),7.88(2h,d,j＝8.5hz,h-3″′,5″′),7.77(2h,brd,j＝7.3hz,h-2″′,6″′),7.52(2h,brt,j＝7.3hz,h-3″′,5″′),7.45(1h,td,j＝7.3/1.1hz,h-4″′).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.2(c-3),101.9(c-4),35.2(c-5),80.0(c-6),58.3(c-7),66.0(c-8),41.9(c-9),58.5(c-l0),97.9(c-l′),73.5(c-2′),77.5(c-3′),70.3(c-4′),76.5(c-5′),61.5(c-6′),121.9(c-1″),112.4(c-2″),152.0(c-3″),148.6(c-4″),112.7(c-5″),123.3(c-6″),165.5(c-7″),55.8(och3),70.6(ar-o-ch2-),133.1(c-1″′),129.2(c-2″′,6″′),127.1(c-3″′,5″′),145.3(c-6″′),193.5(c-7″′),138.9(c-1″″),127.1(c-2″″,6″″),128.7(c-3″″,5″″),128.6(c-6″″).hresims:calcdforc37h37o14[m-h]-705.2189,found:705.2206.
iv-4：1hnmr(500mhz,cd3od):δh5.21(1h,d,j＝9.2hz,h-1),6.39(1h,dd,j＝5.9/1.6hz,h-3),5.02(1h,dd,j＝5.9/4.2hz,h-4),2.66(1h,m,h-5),5.16(1h,dd,j＝7.9/1.1hz,h-6),3.77(1h,d,j＝1.1hz,h-7),2.70(1h,m,h-9),4.19(1h,d,j＝13.2hz,h-10a),3.87(1h,d,j＝13.2hz,h-10b),4.81(1h,d,j＝7.9hz,h-1′),3.28(2h,m,h-2′,4′),3.34(1h,m,h-5′),3.43(1h,t,j＝9.0hz,h-3′),3.66(1h,dd,j＝12.0/6.7hz,h-6′a),3.94(1h,dd,j＝12.0/2.1hz,h-6′b),7.63(1h,d,j＝2.0hz,h-2″),7.07(1h,d,j＝8.5hz,h-5″),7.61(1h,dd,j＝8.5/2.0hz,h-6″),3.88(3h,s,och3″),5.53(2h,s,ar-o-ch2-),7.91(1h,d,j＝8.4hz,h-3″′),7.70(1h,dd,j＝8.4/2.0hz,h-4″′),7.96(1h,d,j＝2.0hz,h-6″′),3.94(3h,s,och3″′).13cnmr(125mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),82.1(c-6),60.4(c-7),67.1(c-8),43.4(c-9),61.4(c-l0),99.9(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.9(c-5′),63.1(c-6′),124.1(c-1″),113.9(c-2″),153.9(c-3″),150.9(c-4″),114.0(c-5″),125.1(c-6″),168.1(c-7″),56.8(och3),69.6(ar-ch2-o-),142.5(c-1″′),128.7(c-2″′),132.1(c-3″′),130.0(c-4″′),128.4(c-5″′),131.9(c-6″′),167.8(c-7″′),53.0(och3″′).hresims:calcdforc32h35brclo15[m+cl]-773.0853,found:773.0871.
iv-5：1hnmr(500mhz,cd3od):δh5.20(1h,d,j＝9.1hz,h-1),6.38(1h,dd,j＝6.0/1.6hz,h-3),5.01(1h,dd,j＝6.0/4.1hz,h-4),2.65(1h,m,h-5),5.14(1h,dd,j＝7.8/1.1hz,h-6),3.77(1h,d,j＝1.1hz,h-7),2.68(1h,m,h-9),4.19(1h,d,j＝13.2hz,h-10a),3.86(1h,d,j＝13.2hz,h-10b),4.81(1h,d,j＝8.0hz,h-1′),3.28(2h,m,h-2′,4′),3.34(1h,m,h-5′),3.42(1h,t,j＝9.0hz,h-3′),3.65(1h,dd,j＝12.0/6.7hz,h-6′a),3.94(1h,dd,j＝12.0/2.1hz,h-6′b),7.57(1h,d,j＝2.0hz,h-2″),7.00(1h,d,j＝8.6hz,h-5″),7.68(1h,dd,j＝8.6/2.0hz,h-6″),3.86(3h,s,och3″),4.90(1h,m,h-1″′),1.97(2h,m,h-2″′,5″′),1.84(4h,m,h-2″′,3″′,4″′,5″′),1.66(2h,m,h-3″′,4″′).13cnmr(125mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),81.9(c-6),60.4(c-7),67.0(c-8),43.4(c-9),61.4(c-l0),99.9(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),122.9(c-1″),114.1(c-2″),153.9(c-3″),151.0(c-4″),114.5(c-5″),125.1(c-6″),167.9(c-7″),56.7(och3),81.8(c-l″′),33.9(c-2″′,5″′),25.1(c-3″′,4″′).hresims:calcdforc28h35o13[m-h]-579.2083,found:579.2080.
iv-6：1hnmr(500mhz,dmso-d6)：δh5.12(1h,d,j＝9.3hz,h-1),6.43(1h,brd,j＝5.6hz,h-3),4.98(1h,brt,j＝5.1hz,h-4),2.59(1h,m,h-5),5.09(1h,brd,j＝8.1hz,h-6),3.71(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,dd,j＝13.2/5.0hz,h-10a),3.73(2h,m,h-10b,6′a),4.62(1h,d,j＝7.8hz,h-1′),3.04(2h,m,h-2′,4′),3.19(2h,m,h-3′,5′),7.49(1h,d,j＝1.2hz,h-2″),7.18(1h,d,j＝8.6hz,h-5″),7.61(1h,dd,j＝8.6/1.2hz,h-6″),3.83(3h,s,och3),5.15(2h,s,ar-ch2-o-),7.28(2h,d,j＝8.2hz,h-2″′,6″′),7.40(2h,d,j＝8.2hz,h-3″′,5″′),2.47(3h,s,sch3).13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.8(c-4),35.2(c-5),79.9(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.8(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.6(c-1″),112.1(c-2″),152.2(c-3″),148.8(c-4″),112.7(c-5″),123.3(c-6″),165.5(c-7″),55.6(och3),69.5(ar-ch2-o-),132.9(c-1″′),125.9(c-2″′,6″′),128.7(c-3″′,5″′),138.1(c-4″′),14.6(sch3).hresims:calcdforc31h35o13s[m-h]-647.1804,found:647.1796.
iv-7：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.6hz,h-1),6.42(1h,dd,j＝5.6/1.6hz,h-3),4.97(1h,dd,j＝5.9/4.7hz,h-4),2.59(1h,m,h-5),5.08(1h,dd,j＝8.1/0.7hz,h-6),3.71(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,dd,j＝13.2/5.0hz,h-10a),3.73(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),7.51(1h,d,j＝1.9hz,h-2″),7.17(1h,d,j＝8.6hz,h-5″),7.62(1h,dd,j＝8.6/1.9hz,h-6″),3.84(3h,s,och3),5.21(2h,s,-ch2-o-),7.73(1h,d,j＝1.8hz,h-2″),7.67(1h,brd,j＝8.3hz,h-5″),7.45(1h,dd,j＝8.3/1.8hz,h-6″).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.2(c-3),101.8(c-4),35.2(c-5),80.0(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.5(c-l0),97.9(c-l′),73.5(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),122.0(c-1″),112.2(c-2″),151.8(c-3″),148.8(c-4″),112.8(c-5″),123.3(c-6″),165.5(c-7″),55.7(och3),68.4(-ch2-o-),137.7(c-1″′),129.7(c-2″′),130.7(c-3″′),131.2(c-4″′),130.8(c-5″′),128.1(c-6″′).hresims:calcdforc30h31cl2o13[m-h]-669.1147,found:669.1155.
iv-8：1hnmr(500mhz,cd3od):δh5.20(1h,d,j＝9.0hz,h-1),6.38(1h,brd,j＝5.9hz,h-3),4.99(1h,m,h-4),2.65(1h,m,h-5),5.14(1h,brd,j＝6.7hz,h-6),3.76(1h,brs,h-7),2.66(1h,m,h-9),4.18(1h,d,j＝13.2hz,h-10a),3.86(1h,d,j＝13.2hz,h-10b),4.81(1h,d,j＝8.0hz,h-1′),3.28(2h,m,h-2′,4′),3.35(1h,m,h-5′),3.43(1h,m,h-3′),3.66(1h,dd,j＝11.9/6.6hz,h-6′a),3.94(1h,dd,j＝11.9/1.9hz,h-6′b),7.60(1h,m,h-2″),7.06(1h,m,h-5″),7.64(1h,m,h-6″),3.90(3h,s,och3″),5.25(2h,s,-ch2-o-),7.64(2h,m,h-2″′,6″′),7.73(2h,m,h-3″′,5″′).13cnmr(125mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),82.1(c-6),60.4(c-7),67.0(c-8),43.4(c-9),61.4(c-l0),99.9(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),122.8(c-1″),113.9(c-2″),153.8(c-3″),150.9(c-4″),114.1(c-5″),125.0(c-6″),167.7(c-7″),56.7(och3),70.8(-ch2-o-),144.0(c-1″′),129.2(c-2″′,6″′),133.6(c-3″′,5″′),112.8(c-4″′),119.8(cn″′).hresims:calcdforc31h33nnao13[m+na]+650.1844,found:650.1839.
iv-9：1hnmr(500mhz,dmso-d6)：δh5.12(1h,d,j＝9.6hz,h-1),6.42(1h,dd,j＝5.9/1.6hz,h-3),4.97(1h,dd,j＝5.9/4.8hz,h-4),2.59(1h,m,h-5),5.08(1h,brd,j＝8.1hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,dd,j＝13.3/4.7hz,h-10a),3.74(2h,m,h-10b,6′a),4.63(1h,d,j＝7.8hz,h-1′),3.05(2h,m,h-2′,4′),3.19(2h,m,h-3′,5′),7.53(1h,d,j＝2.0hz,h-2″),7.22(1h,d,j＝8.6hz,h-5″),7.60(1h,dd,j＝8.6/2.0hz,h-6″),3.88(3h,s,och3),5.46(2h,s,-ch2-o-),7.67(1h,d,j＝8.5hz,h-3″′),8.43(1h,d,j＝8.5hz,h-4″′),8.00(1h,brd,j＝8.5hz,h-6″′),7.63(1h,brt,j＝8.5hz,h-7″′),7.79(1h,brt,j＝8.5hz,h-8″′),8.02(1h,brd,j＝8.5hz,h-9″′).13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.8(c-4),35.2(c-5),80.0(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),122.0(c-1″),112.2(c-2″),152.0(c-3″),148.8(c-4″),112.8(c-5″),123.4(c-6″),165.4(c-7″),55.8(och3),71.4(-ch2-o-),156.9(c-2″′),119.6(c-3″′),137.2(c-4″′),127.3(c-5″′),128.0(c-6″′),126.8(c-7″′),130.0(c-8″′),128.6(c-9″′),147.0(c-10″′).hresims:calcdforc33h36no13[m+h]+654.2181,found:654.2185.
iv-10：1hnmr(500mhz,dmso-d6)：δh5.11(1h,d,j＝9.9hz,h-1),6.43(1h,brd,j＝5.9hz,h-3),4.97(1h,brt,j＝5.2hz,h-4),2.59(1h,m,h-5),5.08(1h,brd,j＝8.1hz,h-6),3.71(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,dd,j＝13.2/5.0hz,h-10a),3.73(2h,m,h-10b,6′a),4.62(1h,d,j＝7.8hz,h-1′),3.04(2h,m,h-2′,4′),3.19(2h,m,h-3′,5′),7.49(1h,brs,h-2″),7.16(1h,d,j＝8.6hz,h-5″),7.61(1h,brd,j＝8.6hz,h-6″),3.83(3h,s,och3),5.16(2h,s,ar-ch2-o-),-),7.26(2h,brd,j＝8.1hz,h-2″′,6″′),7.75(2h,brd,j＝8.1hz,h-3″′,5″′).13cnmr(125mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.8(c-4),35.2(c-5),80.0(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.4(c-l0),97.8(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.8(c-1″),112.1(c-2″),152.0(c-3″),148.8(c-4″),112.7(c-5″),123.3(c-6″),165.4(c-7″),55.7(och3),69.2(-ch2-o-),136.3(c-1″′),130.1(c-2″′,6″′),137.3(c-3″′,5″′),94.2(c-4″′).hresims:calcdforc30h33inao13[m+na]+751.0858,found:751.0858.
iv-11：1hnmr(500mhz,dmso-d6)：δh5.12(1h,d,j＝9.7hz,h-1),6.43(1h,dd,j＝5.9/1.7hz,h-3),4.97(1h,dd,j＝5.7/4.6hz,h-4),2.58(1h,m,h-5),5.08(1h,dd,j＝8.1/0.9hz,h-6),3.71(1h,brs,h-7),2.48(1h,m,h-9),3.92(1h,dd,j＝13.3/5.1hz,h-10a),3.73(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.05(2h,m,h-2′,4′),3.17(2h,m,h-3′,5′),7.49(1h,d,j＝1.9hz,h-2″),7.20(1h,d,j＝8.5hz,h-5″),7.62(1h,dd,j＝8.5/1.9hz,h-6″),3.83(3h,s,och3),5.13(2h,s,-ch2-o-),-),7.21(2h,brd,j＝7.9hz,h-2″′,6″′),7.36(2h,brd,j＝7.9hz,h-3″′,5″′),2.58(2h,t,j＝7.7hz,h-7″),1.54(2h,quint,j＝7.7hz,h-8″),1.31(2h,sext,j＝7.7hz,h-9″),0.89(3h,t,j＝7.7hz,h-10″).13cnmr(125mhz,dmso-d6):δc93.0(c-1),141.1(c-3),101.8(c-4),35.2(c-5),80.0(c-6),58.2(c-7),65.9(c-8),41.8(c-9),58.3(c-l0),97.9(c-l′),73.4(c-2′),77.5(c-3′),70.2(c-4′),76.4(c-5′),61.3(c-6′),121.9(c-1″),112.0(c-2″),152.7(c-3″),148.8(c-4″),113.1(c-5″),123.5(c-6″),165.5(c-7″),55.5(och3),63.0(-ch2-o-),133.6(c-1″′),128.1(c-2″′,6″′),128.4(c-3″′,5″′),142.3(c-4″′),34.6(c-7″′),33.1(c-8″′),21.7(c-9″′),13.8(c-10″′).hresims:calcdforc34h42nao13[m+na]+681.2518,found:681.2522.
iv-12：1hnmr(500mhz,dmso-d6+d2o)：δh5.12(1h,d,j＝9.7hz,h-1),6.42(1h,dd,j＝5.9/1.6hz,h-3),4.98(1h,dd,j＝5.9/4.6hz,h-4),2.60(1h,m,h-5),5.10(1h,dd,j＝8.1/1.0hz,h-6),3.72(1h,brs,h-7),2.52(1h,m,h-9),3.94(1h,d,j＝13.3hz,h-10a),3.71(2h,m,h-10b,6′a),4.62(1h,d,j＝7.8hz,h-1′),3.05(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),7.48(1h,d,j＝2.0hz,h-2″),7.74(1h,dd,j＝8.4/2.0hz,h-6″),3.67(3h,s,och3),6.10(2h,s,-ch2-o-),8.29(2h,d,j＝8.9hz,h-1″′,8″′),7.58(5h,m,h-5″,2″′,3″′,6″′,7″′),8.16(2h,d,j＝8.0hz,h-4″′,5″′),8.73(1h,s,h-10″′).13cnmr(125mhz,dmso-d6+d2o):δc93.4(c-1),141.5(c-3),102.1(c-4),35.2(c-5),80.3(c-6),58.7(c-7),66.2(c-8),42.0(c-9),58.8(c-l0),98.2(c-l′),73.6(c-2′),77.6(c-3′),70.4(c-4′),76.4(c-5′),61.5(c-6′),122.2(c-1″),112.3(c-2″),153.1(c-3″),149.1(c-4″),113.4(c-5″),123.9(c-6″),166.0(c-7″),55.8(och3),63.3(-ch2-o-),127.3(c-1″′,8″′),125.8(c-2″′,7″′),124.3(c-3″′,6″′),129.3(c-4″′,5″′),126.9(c-9″′),129.3(c-10″′),131.0(c-4a″′,10a″′),131.3(c-7a″′,8a″′).hresims:calcdforc38h37o13[m-h]-701.2240,found:701.2247.
iv-13：1hnmr(500mhz,cd3od):δh5.19(1h,d,j＝9.2hz,h-1),6.37(1h,dd,j＝5.9/1.4hz,h-3),5.02(1h,dd,j＝5.9/4.1hz,h-4),2.68(1h,m,h-5),5.14(1h,dd,j＝7.8/1.0hz,h-6),3.76(1h,s,h-7),2.65(1h,m,h-9),4.18(1h,d,j＝13.2hz,h-10a),3.86(1h,d,j＝13.2hz,h-10b),4.81(1h,d,j＝7.9hz,h-1′),3.28(2h,m,h-2′,4′),3.34(1h,m,h-5′),3.42(1h,t,j＝9.0hz,h-3′),3.66(1h,dd,j＝12.0/6.6hz,h-6′a),3.94(1h,dd,j＝12.0/2.0hz,h-6′b),7.58(1h,d,j＝2.0hz,h-2″),7.03(1h,d,j＝8.5hz,h-5″),7.64(1h,dd,j＝8.5/2.0hz,h-6″),3.89(3h,s,och3″),5.10(2h,s,-o-ch2-),6.60(2h,d,j＝2.2hz,h-2″′,6″′),6.41(1h,t,j＝2.2hz,h-4″′),3.76(6h,s,och3″′×2).13cnmr(125mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),82.0(c-6),60.4(c-7),67.0(c-8),43.4(c-9),61.4(c-l0),99.9(c-l′),75.0(c-2′),78.8(c-3′),71.9(c-4′),77.8(c-5′),63.1(c-6′),123.7(c-1″),113.9(c-2″),154.2(c-3″),150.8(c-4″),114.1(c-5″),125.0(c-6″),167.8(c-7″),56.7(och3),71.8(-ch2-o-),140.5(c-1″′),106.4(c-2″′,6″′),162.7(c-3″′,5″′),100.9(c-4″′),55.9(2×och3″′).hresims:calcdforc32h37o15[m-h]-661.2138,found:661.2149.
iv-14：1hnmr(500mhz,dmso-d6+d2o)：δh5.10(1h,d,j＝9.7hz,h-1),6.42(1h,dd,j＝5.9/1.7hz,h-3),4.96(1h,dd,j＝5.8/4.6hz,h-4),2.58(1h,m,h-5),5.08(1h,dd,j＝8.0/1.0hz,h-6),3.70(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,d,j＝13.3hz,h-10a),3.71(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.03(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.42(1h,dd,j＝12.0/6.9hz,h-6′b),7.51(1h,d,j＝1.9hz,h-2″),7.17(1h,d,j＝8.5hz,h-5″),7.61(1h,dd,j＝8.5/1.9hz,h-6″),3.85(3h,s,och3),5.36(2h,s,-ch2-o-),-),7.72(2h,d,j＝8.8hz,h-2″′,6″′),8.26(1h,brd,j＝8.8hz,h-3″′,5″′).13cnmr(125mhz,dmso-d6+d2o):δc93.1(c-1),141.3(c-3),101.9(c-4),35.3(c-5),80.2(c-6),58.4(c-7),66.0(c-8),41.9(c-9),58.5(c-l0),98.0(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.3(c-5′),61.4(c-6′),122.2(c-1″),112.3(c-2″),151.9(c-3″),149.0(c-4″),113.0(c-5″),123.5(c-6″),165.6(c-7″),55.9(och3),68.9(-ch2-o-),144.5(c-1″′),128.6(c-2″′,6″′),123.8(c-3″′,5″′),147.3(c-4″′).hresims:calcdforc30h32no15[m-h]-646.1777,found:646.1787.
iv-15：1hnmr(500mhz,cd3od):δh5.21(1h,d,j＝9.2hz,h-1),6.39(1h,dd,j＝5.9/1.4hz,h-3),5.02(1h,dd,j＝5.9/4.1hz,h-4),2.70(1h,m,h-5),5.15(1h,dd,j＝7.9/1.0hz,h-6),3.77(1h,brs,h-7),2.65(1h,m,h-9),4.19(1h,d,j＝13.2hz,h-10a),3.86(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.9hz,h-1′),3.27(2h,m,h-2′,4′),3.41(1h,t,j＝9.0hz,h-3′),3.65(1h,dd,j＝11.9/6.6hz,h-6′a),3.94(1h,dd,j＝11.9/2.0hz,h-6′b),7.62(1h,d,j＝2.0hz,h-2″),7.25(1h,d,j＝8.5hz,h-5″),7.72(1h,dd,j＝8.5/2.0hz,h-6″),3.85(3h,s,och3″),5.63(2h,s,-o-ch2-),7.64(1h,brd,j＝7.2hz,h-2″′),7.47(1h,brt,j＝7.2hz,h-3″′),8.12(1h,brd,j＝7.2hz,h-4″′),7.88(1h,brd,j＝8.2hz,h-5″′),7.54(2h,m,h-6″′,7″′),7.91(1h,brd,j＝8.2hz,h-2″′).13cnmr(125mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),82.1(c-6),60.4(c-7),67.1(c-8),43.4(c-9),61.4(c-l0),99.9(c-l′),75.0(c-2′),78.8(c-3′),72.0(c-4′),77.9(c-5′),63.1(c-6′),123.9(c-1″),114.1(c-2″),154.4(c-3″),151.1(c-4″),114.4(c-5″),125.0(c-6″),167.8(c-7″),56.7(och3),70.7(-ch2-o-),133.1(c-1″′),128.0(c-2″′),126.4(c-3″′),129.8(c-4″′),135.4(c-4a″′),130.3(c-5″′),127.6(c-6″′),127.1(c-7″′),125.1(c-8″′),133.5(c-8a″′).hresims:calcdforc34h35o13[m-h]-651.2083,found:651.2087.
iv-16：1hnmr(500mhz,cd3od):δh5.20(1h,d,j＝9.1hz,h-1),6.38(1h,brd,j＝5.8hz,h-3),5.00(1h,dd,j＝5.8/4.2hz,h-4),2.69(1h,m,h-5),5.15(1h,brd,j＝7.5hz,h-6),3.76(1h,brs,h-7),2.64(1h,m,h-9),4.19(1h,d,j＝13.2hz,h-10a),3.85(1h,d,j＝13.2hz,h-10b),4.80(1h,d,j＝7.9hz,h-1′),3.26(2h,m,h-2′,4′),3.41(1h,t,j＝9.0hz,h-3′),3.65(1h,dd,j＝11.9/6.6hz,h-6′a),3.92(1h,m,h-6′b),7.61(1h,d,j＝1.6hz,h-2″),7.12(1h,d,j＝8.5hz,h-5″),7.68(1h,dd,j＝8.5/1.6hz,h-6″),3.91(3h,s,och3″),5.25(2h,s,-o-ch2-),7.30(2h,d,j＝8.0hz,h-2″′,6″′),7.50(2h,d,j＝8.0hz,h-3″′,5″′),7.40(1h,brd,j＝7.5hz,h-3″″),7.57(1h,brt,j＝7.5hz,h-4″″),7.44(1h,brt,j＝7.5hz,h-5″″),7.76(1h,brd,j＝7.5hz,h-6″″).13cnmr(125mhz,cd3od):δc95.2(c-1),142.6(c-3),103.1(c-4),36.9(c-5),82.0(c-6),60.4(c-7),67.1(c-8),43.4(c-9),61.4(c-l0),99.9(c-l′),75.0(c-2′),78.8(c-3′),72.0(c-4′),77.9(c-5′),63.1(c-6′),123.8(c-1″),114.0(c-2″),154.3(c-3″),150.9(c-4″),114.2(c-5″),125.0(c-6″),167.8(c-7″),56.7(och3),71.7(-o-ch2-),142.6(c-1″′),128.7(c-2″′,6″′),129.8(c-3″′,5″′),143.3(c-4″′),137.3(c-1″″),132.6(c-2″″),131.9(c-3″″),130.8(c-4″″),132.7(c-5″″),128.6(c-6″″),171.1(c-7″″),52.6(och3″″).hresims:calcdforc38h40nao15[m-h]-759.2259,found:759.2252.
iv-17：1hnmr(500mhz,dmso-d6+d2o)：δh5.10(1h,d,j＝9.5hz,h-1),6.41(1h,dd,j＝5.9/1.6hz,h-3),4.96(1h,dd,j＝5.9/4.6hz,h-4),2.57(1h,m,h-5),5.07(1h,dd,j＝8.0/1.0hz,h-6),3.69(1h,brs,h-7),2.47(1h,m,h-9),3.92(1h,d,j＝13.3hz,h-10a),3.71(2h,m,h-10b,6′a),4.61(1h,d,j＝7.9hz,h-1′),3.04(2h,m,h-2′,4′),3.18(2h,m,h-3′,5′),3.42(1h,dd,j＝12.0/6.9hz,h-6′b),7.50(1h,d,j＝2.0hz,h-2″),7.17(1h,d,j＝8.5hz,h-5″),7.61(1h,dd,j＝8.5/2.0hz,h-6″),3.83(3h,s,och3),5.31(2h,s,-ch2-o-),7.70(2h,d,j＝8.3hz,h-2″′,6″′),7.94(2h,d,j＝8.3hz,h-3″′,5″′),3.19(3h,s,so2ch3).13cnmr(125mhz,dmso-d6+d2o):δc93.3(c-1),141.4(c-3),102.0(c-4),35.4(c-5),80.3(c-6),58.6(c-7),66.2(c-8),42.0(c-9),58.7(c-l0),98.1(c-l′),73.5(c-2′),77.6(c-3′),70.4(c-4′),76.4(c-5′),61.5(c-6′),122.3(c-1″),112.4(c-2″),152.1(c-3″),149.1(c-4″),113.1(c-5″),123.7(c-6″),165.8(c-7″),56.0(och3),69.2(-ch2-o-),142.7(c-1″′),127.5(c-2″′,6″′),128.6(c-3″′,5″′),140.5(c-4″′),43.8(so2ch3″′).hresims:calcdforc31h35o15s[m-h]-679.1702,found:679.1718.
iv-18：1hnmr(500mhz,dmso-d6)：δh5.09(1h,d,j＝9.6hz,h-1),6.40(1h,dd,j＝5.9/1.6hz,h-3),4.96(1h,dd,j＝5.9/4.5hz,h-4),2.57(1h,m,h-5),5.07(1h,dd,j＝8.0/1.0hz,h-6),3.69(1h,brs,h-7),2.47(1h,m,h-9),3.94(1h,d,j＝13.2hz,h-10a),3.71(2h,m,h-10b,6′a),4.62(1h,d,j＝7.9hz,h-1′),3.06(2h,m,h-2′,4′),3.20(2h,m,h-3′,5′),3.43(1h,dd,j＝11.8/6.8hz,h-6′b),7.49(1h,d,j＝2.0hz,h-2″),7.20(1h,d,j＝8.5hz,h-5″),7.61(1h,dd,j＝8.5/2.0hz,h-6″),3.82(3h,s,och3),5.20(2h,s,-ch2-o-),7.82(2h,brd,j＝8.6hz,h-2″′,6″′),7.56(2h,brd,j＝8.6hz,h-3″′,5″′),7.73(1h,d,j＝1.7hz,h-3″″),6.53(1h,dd,j＝1.7/1.5hz,h-4″″),8.43(1h,d,j＝1.5hz,h-5″″).13cnmr(125mhz,dmso-d6):δc93.4(c-1),141.5(c-3),102.1(c-4),35.5(c-5),80.3(c-6),58.7(c-7),66.2(c-8),42.0(c-9),58.7(c-l0),98.2(c-l′),73.7(c-2′),77.6(c-3′),70.5(c-4′),76.6(c-5′),61.6(c-6′),122.0(c-1″),112.4(c-2″),152.5(c-3″),149.1(c-4″),113.1(c-5″),123.8(c-6″),165.9(c-7″),56.0(och3),69.8(-ch2-o-),139.7(c-1″′),129.6(c-2″′,6″′),118.8(c-3″′,5″′),134.6(c-4″′),141.5(c-3″″),108.4(c-4″″),128.1(c-5″″).hresims:calcdforc33h37n2o13[m+h]+669.2290,found:669.2301.
iv-19：1hnmr(400mhz,dmso-d6)：δh5.10(1h,d,j＝9.6hz,h-1),6.41(1h,dd,j＝5.9/1.6hz,h-3),4.95(1h,dd,j＝5.9/4.6hz,h-4),2.56(1h,m,h-5),5.04(1h,m,h-6),3.68(1h,brs,h-7),2.45(1h,m,h-9),3.90(1h,m,h-10a),3.72(2h,m,h-10b,6′a),4.61(1h,d,j＝7.8hz,h-1′),3.03(2h,m,h-2′,4′),3.17(2h,m,h-3′,5′),3.43(1h,dd,j＝12.0/6.9hz,h-6′b),7.49(1h,d,j＝2.0hz,h-2″,6″,2″′,6″′,2″″,6″″),7.09(1h,d,j＝8.5hz,h-5″),3.90(3h,s,och3),6.68(1h,s,-ch-o-),7.36(4h,t,j＝7.5hz,h-c-3″′,5″′,c-3″″,5″″),7.27(2h,s,t,j＝7.5hz,h-4″″,4″″).13cnmr(100mhz,dmso-d6):δc92.9(c-1),141.1(c-3),101.8(c-4),35.1(c-5),79.9(c-6),58.1(c-7),65.8(c-8),41.8(c-9),58.4(c-l0),97.8(c-l′),73.4(c-2′),77.5(c-3′),70.3(c-4′),76.4(c-5′),61.4(c-6′),121.9(c-1″),112.4(c-2″),151.0(c-3″),149.3(c-4″),114.6(c-5″),123.0(c-6″),165.3(c-7″),55.9(och3),80.4(-ch-o-),140.9(c-1″′,1″″),126.5(c-2″′,6″′,2″″,6″″),128.6(c-3″′,5″′,c-3″″,5″″),127.8(c-4″″,4″″).hresims:calcdforc36h38nao13[m+na]+701.2205,found:701.2205.
实施例5：式i、ii、iii和iv类化合物对ogg1的抑制作用
待测化合物与含有重组人ogg1蛋白(abcam)(详细检查方法可参考已发表文献：acschembiol.2015,10(10):2334-43.)。在384孔板中加入五个不同浓度待测样品(包括阳性对照组：ogg1inhibitoro8)的10μl缓冲液(20mmtris-hcl,100mmkcl,0.1％bsa,0.01％tween-20,ph7.5)，并设置空白对照。随后加入20nl浓度为12.5μm的ogg1，室温共孵育5min。随后加入20nl的12.5μm8-oxo-gua溶液后37℃孵育40min，使用全波长扫描式多功能读数仪(filters＝ex528/20,em600/40.mirror＝top570nmwithpolarizer)进行检测，每个样品平行检测三次。
具体数值见表2，通过表2可知：
本发明所述的式i和式ii化合物对ogg1活性具有一定的抑制作用，同时发现梓醇6位连有较大的芳香性基团时(i-3)，抑制ogg1的作用显著提高。进而通过梓苷和胡黄连苷ii间接在梓醇6位引入其他基团来探讨其对ogg1的抑制活性，发现式iii和式iv化合物抑制ogg1的活性都比梓苷或胡黄连苷ii显著提高。因此，本发明所述的梓醇衍生物或/和其可药用衍生物作为活性成分用于制备预防、缓解和/或治疗由ogg1活化所引起的疾病的药物和保健食品。
表2梓醇类衍生物对ogg1的抑制作用
*阳性对照
最后有必要在此说明的是：以上实施例只用于对本发明的技术方案作进一步详细地说明，不能理解为对本发明保护范围的限制，本领域的技术人员根据本发明的上述内容作出的一些非本质的改进和调整均属于本发明的保护范围。