CN105085461B - 一类黄烷化合物，其制备方法及降糖活性 - Google Patents
一类黄烷化合物，其制备方法及降糖活性 Download PDFInfo
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- CN105085461B CN105085461B CN201410215130.7A CN201410215130A CN105085461B CN 105085461 B CN105085461 B CN 105085461B CN 201410215130 A CN201410215130 A CN 201410215130A CN 105085461 B CN105085461 B CN 105085461B
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Abstract
本发明公开一类如通式I所示的黄烷化合物，其制备方法及其在治疗和/或预防肥胖症以及糖尿病和糖耐量异常药物和保健品中的应用。该类黄烷化合物是由大花红景天中的黄烷聚合物(以ECG为聚合单元)和狭叶红景天中的黄烷聚合物(以EGCG为聚合单元)经连接有不同功能基团的硫解试剂衍生化后得到的。药理结果显示，此类黄烷化合物在降糖方面具有较好的药理学作用。
Description
技术领域
本发明涉及医药技术领域，一类黄烷化合物，其制备方法及其在抗糖尿病方面的药物和保健品用途。
背景技术
糖尿病是一种常见的内分泌代谢紊乱行疾病，糖尿病及其并发症是威胁人类健康的主要疾病，死亡率仅次于肿瘤和心血管疾病。目前，糖尿病血管病变的发生机制尚未完全确定，主要的理论有非酶糖化学说、氧化应激学说和新号传导学说。目前已上市的降糖药主要分为以下几种类型：α-葡萄糖苷酶抑制剂、噻唑烷酮类、双胍类、磺酰脲类、瑞格列奈类、二肽基肽酶-4抑制剂，它们均显示不同的毒副作用，比较典型的为噻唑烷酮类的吡格列酮，目前FDA已禁用。因此，寻找高效低毒的降糖药具有重要的意义。
α-葡萄糖苷酶位于小肠内皮刷状缘内，其主要作用是促进肠道对淀粉糊精、多糖、蔗糖及麦芽糖的分解和吸收，并将其它低聚糖分解为右旋葡萄糖、半乳糖和右旋果糖等。α-葡萄糖苷酶抑制剂通过可逆性抑制刷状缘α-葡萄糖苷酶(包括淀粉酶、麦芽糖酶、蔗糖酶、异麦芽糖酶等)延迟多糖、双糖转化成可吸收的单糖，减轻餐后血糖的升高。另外，正常情况下低位小肠已无食物成分，服用α-葡萄糖苷酶抑制类药后，肠内碳水化合物、脂肪、蛋白质等食糜可进入回肠远端，该部位是小肠胰升糖素样肽-1(GLP-1)贮量最丰富的位置，可以刺激GLP-1分泌增加，刺激胰岛素的释放，从而降低餐后血糖浓度，α-葡萄糖苷酶抑制剂是比较成熟的治疗糖尿病药物，已广泛应用于临床。
黄烷及其聚合物是广泛存在于传统药用植物中的一类化学成分，药理活性研究结果表明，黄烷类化合物具有降糖、神经保护、抗氧化、抗菌、抗病毒、抗炎等方面的活性，而黄烷聚合物近年来虽有活性方面的报道，但其研究尚未成熟，且其结构复杂，单体化合物不易提纯。文献报道，黄烷聚合物可以通过硫解的方法进行降解，得到4位被硫代的黄烷衍生物，但由于产物比较复杂，不易分离纯化，因此目前已报道的黄烷衍生物中4位被杂原子取代的衍生物较少。
本课题在前期研究的基础上，发现红景天中黄烷聚合物的聚合单元比较单一，且其黄烷3位均被没食子酰化，硫解后产物比较单一，易分离纯化，目前尚未有此类黄烷衍生物在药理活性方面的报道，因此对此类聚合物进行了进一步的衍生化合成，得到一系列已黄烷为母核的硫代衍生化物，并对其抗糖尿病活性进行了评价，药理结果显示此类衍生物具有较好的α-葡萄糖苷酶抑制活性，在对小鼠口服蔗糖耐量的影响方面，与阿卡波糖的作用类似，黄烷衍生物JP-3、JP-7、JP-12、JP-16、JP-22、JP-47可明显减少正常小鼠蔗糖负荷后的血糖升高，使血糖-时间曲线下面积AUC值明显降低。
发明内容
本发明的目的在于提供一类黄烷化合物。
本发明的另一目的在于提供一类黄烷化合物的制备方法。
本发明的再一目的在于提供一种药物组合物，其包括至少一个上述黄烷化合物及药用载体和/或赋形剂。
本发明的又一目的在于提供一类黄烷化合物在制备用于预防和/或治疗肥胖症的药物和保健品中的应用。
本发明的又一目的在于提供一类黄烷化合物在制备用于预防和/或治疗糖尿病和糖耐量异常的药物和保健品中的应用。
为解决本发明的技术问题，本发明采用如下技术方案：
本发明所述的一类黄烷化合物如通式I所示：
其中，通式I中R1选自-H、-OH；
其中，通式I中R选自取代的苄基，取代或非取代的芳杂环乙基，取代或非取代的芳杂环甲基，取代或非取代的苯，取代或非取代的脂肪基，取代或非取代的羧酸酯；
上述的“取代的苄基”指的是取代基个数为1～5的苄基，其取代基选自氢、C1～5的烷基、C1～5的烯基、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代或非取代的芳杂环乙基”指的是杂原子个数为1～3的五元或六元芳杂环乙基，其芳杂环的杂原子选自N、O、S，取代基选自氢、C1～5的烷基、C1～5的烯基、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代或非取代的芳杂环甲基”指的是杂原子个数为1～3的五元或六元芳杂环甲基，其芳杂环的杂原子选自N、O、S，取代基选自氢、C1～5的烷基、C1～5的烯基、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代的苯”指的是取代基个数为1～5的苯基，其取代基选自氢、C1～5的烷基、C1～5的烯基、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代或非取代的脂肪基”中脂肪基选自C1～5的直链或支链烷基、C1～5的直链或支链烯基、C5～6的环烷基，其取代基选自氢、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代或非取代的羧酸酯”指的是羧酸链和酯基链均为C1～5的直链或支链烷基、C1～5的直链或支链烯基，其中羧酸链和酯基链可以相同，也可以不同，其取代基选自氢、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
其中，上述的“Ra”指的是C1～5的直链或支链烷基、C1～5的直链或支链烯基。
以下提供本发明化合物各种基团的定义，除另行定义外，它们在说明书和权利要求书中统一使用。
“取代基个数为1～5”指的是取代基个数为1、2、3、4、5个。
“C1～5的直链或支链烷基”指的是含有1、2、3、4、5个碳原子的直链或支链烷基，优选甲基、乙基、丁基、异丙基。
“C1～5的直链或支链烯基”指的是含有1、2、3、4、5个碳原子的直链或支链烯基，优选烯丙基。
“C1～5的烷氧基”指的是含有1、2、3、4、5个碳原子的直链或支链烷烃通过与氧原子相连，优选甲氧基、乙氧基、丙氧基、丁氧基、异丁氧基。
“C5～6的环烷基”指的是含有5、6个碳原子的环状烷基，优选环戊基、环己基。
根据本发明优选的通式I所示的化合物包括，但不限定于通式Ia所示的化合物：
其中，R1选自H、OH；
其中，R2、R3、R4、R5、R6独立的选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基，并且R2、R3、R4、R5、R6不同时为氢。
根据本发明优选的通式I所示的R包括，但不限定于取代或非取代的吡嗪乙基、取代或非取代的嘧啶乙基、取代或非取代的哌嗪乙基、取代或非取代的吡啶乙基、取代或非取代的呋喃乙基、取代或非取代的吡咯乙基、取代或非取代的噻吩乙基、取代或非取代的噻唑乙基；
其中，取代基选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基。
根据本发明优选的通式I所示的化合物包括，但不限定于通式Ib所示的化合物：
其中，R1选自H、OH；
其中，R7、R8、R9独立的选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基。
根据本发明优选的通式I所示的R包括，但不限定于取代或非取代的吡嗪甲基、取代或非取代的嘧啶甲基、取代或非取代的哌嗪甲基、取代或非取代的吡啶甲基、取代或非取代的呋喃甲基、取代或非取代的吡咯甲基、取代或非取代的噻吩甲基、取代或非取代的噻唑甲基；
其中，取代基选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基。
根据本发明优选的通式I所示的化合物包括，但不限定于通式Ic所示的化合物：
其中，R1选自H、OH；
其中，R10、R11、R12独立的选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基。
根据本发明优选的通式I所示的化合物包括，但不限定于通式Id所示的化合物：
其中，R1选自H、OH；
其中，R13、R14、R15、R16、R17独立的选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基，并且R13、R14、R15、R16、R17不同时为氢。
本发明优选的通式I所示的R包括，但不限定于甲基、乙基、丁基、异丙基、丙烯基、异丙烯基、丁烯基、环戊基、环己基、3-甲基丁基-2-基。
本发明优选的通式I所示的R包括，但不限定于如下羧酸酯类取代基：
羧酸酯类取代基
。
本发明优选的化合物包括，但不限定于以下结构：
R1＝H的化合物结构与名称
R1＝OH的化合物结构与名称
。
本发明第二方面提供了制备本发明黄烷化合物的方法。
该类衍生物是通过对天然产物中的黄烷聚合物进行衍生化反应后分离纯化得到的。具体通过以下几个步骤实现：
1)该部位的提取参照之前中国专利，专利申请号为201010587820.7的红景天有效部位的提取方法，将含有黄烷聚合物的中药材粉碎，用6-12倍量的有机溶剂提取2-5次；将提取液过滤后进行减压浓缩，除去溶剂，即得药材总提取物；
2)将药材总提取物进行大孔吸附树脂柱分离，洗脱液减压浓缩，经冷冻干燥后即得黄烷聚合物部位；
3)将黄烷聚合物部位通过加入不同的硫代试剂(R-SH)进行硫解反应。
步骤1)中优选的有机溶剂选自甲醇、乙醇或丙酮。甲醇、乙醇或丙酮的优选浓度为30-95％(和水的混合物的质量比)；
步骤1)中为加快提交效率，提取方式优选采用50-80℃；
步骤1)中优选的含有黄烷聚合物的中药材选自原料药材选自大花红景天、狭叶红景天、高山红景天、玫瑰红景天、德钦红景天、喜马红景天、帕里红景天、菱叶红景天、四裂红景天、云南红景天、大株红景天、长鞭红景天、唐古特红景天、圣地红景天、小丛红景天、库页红景天儿茶、虎杖、大黄、密花豆、桂皮、钩藤、金鸡纳皮。
步骤2)中大孔吸附树脂柱所选流动相优选为纯水-95％乙醇梯度系统；每个梯度的洗脱体积为2-4个柱体积；
步骤2)中优选的大孔树脂选自弱极性或中性大孔树脂；
步骤2)中更优选的大孔树脂选自Diaion HP-10、20、30、40、50、DM301、NKA-9、AB-8、D101、DM130、LSA-10、LSA-20、DM-18、D312。
步骤3)中的反应通式如路线1所示：
其中，R、R1的定义与通式I中的R、R1相同；
步骤3)中还包括分离纯化步骤：取一定量的黄烷聚合物溶于质量比1:30的无水甲醇中，然后加入质量比1:0.5的硫代试剂，质量比1:0.5的48％的HBr水溶液，加热搅拌于60℃条件下反应4h后，HPLC监测反应完毕。向反应液中加入与反应液质量比5:1的蒸馏水，乙酸乙酯萃取3次，合并有机层，有机层经无水硫酸钠干燥后，浓缩至干燥得到粗品。粗品经200-300目的硅胶柱粗分后，进行LH-20柱色谱分离，用质量分数MeOH:H2O＝30％～70％的甲醇水溶液为流动相，高压制备液相得到相应的4-位被硫代的黄烷衍生物，其中质量比1:30指的是黄烷聚合物和无水甲醇的质量比，质量比1:0.5指的是黄烷聚合物和硫代试剂的质量比，质量比1:0.5指的是黄烷聚合物和48％氢溴酸水溶液的质量比；
步骤3)中所述R的定义与通式I的R相同。
本发明第三方面涉及以本发明化合物作为活性成份的药物组合物。该药物组合物可根据本领域公知的方法制备。可通过将本发明化合物与一种或多种药学上可接受的固体或液体赋形剂和/或辅剂结合，制成适于人或动物使用的任何剂型。本发明化合物在其药物组合物中的含量通常为0.1-95重量％。
本发明化合物或含有它的药物组合物可以单位剂量形式给药，给药途径可为肠道或非肠道，如口服、静脉注射、肌肉注射、皮下注射、鼻腔、口腔粘膜、眼、肺和呼吸道、皮肤、阴道、直肠等。
给药剂型可以是液体剂型、固体剂型或半固体剂型。液体剂型可以是溶液剂(包括真溶液和胶体溶液)、乳剂(包括o/w型、w/o型和复乳)、混悬剂、注射剂(包括水针剂、粉针剂和输液)、滴眼剂、滴鼻剂、洗剂和搽剂等；固体剂型可以是片剂(包括普通片、肠溶片、含片、分散片、咀嚼片、泡腾片、口腔崩解片)、胶囊剂(包括硬胶囊、软胶囊、肠溶胶囊)、颗粒剂、散剂、微丸、滴丸、栓剂、膜剂、贴片、气(粉)雾剂、喷雾剂等；半固体剂型可以是软膏剂、凝胶剂、糊剂等。
本发明化合物可以制成普通制剂、也制成是缓释制剂、控释制剂、靶向制剂及各种微粒给药系统。
为了将本发明化合物制成片剂，可以广泛使用本领域公知的各种赋形剂，包括稀释剂、黏合剂、润湿剂、崩解剂、润滑剂、助流剂。稀释剂可以是淀粉、糊精、蔗糖、葡萄糖、乳糖、甘露醇、山梨醇、木糖醇、微晶纤维素、硫酸钙、磷酸氢钙、碳酸钙等；湿润剂可以是水、乙醇、异丙醇等；粘合剂可以是淀粉浆、糊精、糖浆、蜂蜜、葡萄糖溶液、微晶纤维素、阿拉伯胶浆、明胶浆、羧甲基纤维素钠、甲基纤维素、羟丙基甲基纤维素、乙基纤维素、丙烯酸树脂、卡波姆、聚乙烯吡咯烷酮、聚乙二醇等；崩解剂可以是干淀粉、微晶纤维素、低取代羟丙基纤维素、交联聚乙烯吡咯烷酮、交联羧甲基纤维素钠、羧甲基淀粉钠、碳酸氢钠与枸橼酸、聚氧乙烯山梨糖醇脂肪酸酯、十二烷基磺酸钠等；润滑剂和助流剂可以是滑石粉、二氧化硅、硬脂酸盐、酒石酸、液体石蜡、聚乙二醇等。
还可以将片剂进一步制成包衣片，例如糖包衣片、薄膜包衣片、肠溶包衣片，或双层片和多层片。
为了将给药单元制成胶囊剂，可以将有效成分本发明化合物与稀释剂、助流剂混合，将混合物直接置于硬胶囊或软胶囊中。也可将有效成分本发明化合物先与稀释剂、黏合剂、崩解剂制成颗粒或微丸，再置于硬胶囊或软胶囊中。用于制备本发明化合物片剂的各稀释剂、黏合剂、润湿剂、崩解剂、助流剂品种也可用于制备本发明化合物的胶囊剂。
为将本发明化合物制成注射剂，可以用水、乙醇、异丙醇、丙二醇或它们的混合物作溶剂并加入适量本领域常用的增溶剂、助溶剂、pH调剂剂、渗透压调节剂。增溶剂或助溶剂可以是泊洛沙姆、卵磷脂、羟丙基-β-环糊精等；pH调剂剂可以是磷酸盐、醋酸盐、盐酸、氢氧化钠等；渗透压调节剂可以是氯化钠、甘露醇、葡萄糖、磷酸盐、醋酸盐等。如制备冻干粉针剂，还可加入甘露醇、葡萄糖等作为支撑剂。
此外，如需要，也可以向药物制剂中添加着色剂、防腐剂、香料、矫味剂或其它添加剂。
为达到用药目的，增强治疗效果，本发明的药物或药物组合物可用任何公知的给药方法给药。
本发明化合物药物组合物的给药剂量依照所要预防或治疗疾病的性质和严重程度，患者或动物的个体情况，给药途径和剂型等可以有大范围的变化。一般来讲，本发明化合物的每天的合适剂量范围为0.001-150mg/Kg体重，优选为0.1-100mg/Kg体重，更优选为1-60mg/Kg体重，最优选为2-30mg/Kg体重。上述剂量可以一个剂量单位或分成几个剂量单位给药，这取决于医生的临床经验以及包括运用其它治疗手段的给药方案。
本发明的化合物或组合物可单独服用，或与其他治疗药物或对症药物合并使用。当本发明的化合物与其它治疗药物存在协同作用时，应根据实际情况调整它的剂量。
本发明第四方面涉及上述黄烷化合物制备用于预防和/或治疗肥胖症、糖尿病和糖耐量异常的药物和保健品中的应用。
实验证明本发明所述的化合物在评价降糖药物疗效的动物模型如大鼠口服蔗糖耐量的影响方面显示出较好的降糖活性，该模型适用于肥胖症、糖尿病和糖耐量异常。
本发明化合物和药物组合物的适应症，主要包括一切与高血糖有关的疾病，如：肥胖症、糖尿病和糖耐量异常。
有益技术效果：
1.本发明的化合物结构新颖，均未见文献报道，具有进一步开发成降糖方面新药的潜力。
2.本发明的化合物具有较好的降糖活性，在对α-葡萄糖苷酶的抑制活性方面，此类化合物均具有较好的药理活性，此类化合物的IC50均在10μM以下，而阳性对照药的IC50为500μM，在对小鼠口服蔗糖耐量的影响方面，与阿卡波糖的作用类似，黄烷衍生物JP-3、JP-7、JP-12、JP-16、JP-22、JP-47可明显减少正常小鼠蔗糖负荷后的血糖升高，使血糖-时间曲线下面积AUC值明显降低。目前，未见此类化合物在α-葡萄糖苷酶的抑制活性方面的报道。
3.此类化合物合成路线成熟，简单易得。
附图说明：
图1,本发明化合物对小鼠蔗糖负荷后的血糖水平的影响；
图2,本发明化合物对小鼠蔗糖负荷后血糖-时间曲线下面积AUC；
图3,本发明化合物对小鼠蔗糖负荷后的血糖水平的影响；
图4,本发明化合物对小鼠蔗糖负荷后血糖-时间曲线下面积AUC
具体实施方式
下面的实施例及药理活性实验用于进一步说明本发明，但这并不意味着对本发明的任何限制。
1.黄烷衍生物的制备方法
制备例1黄烷聚合物部位的提取
该部位的提取参照之前中国专利，申请号为201010587820.7的红景天有效部位的提取方法，采集大花红景天及狭叶红景天各20kg，80％乙醇提取3次后浓缩，得到浸膏，然后向浸膏中加入质量比10倍量的蒸馏水于10℃左右静置96h，上清液浓缩后经依次经水、5％乙醇、50％乙醇、95％乙醇四个梯度进行大孔树脂分离，取50％水-乙醇部位，浓缩冷冻干燥，得到两种富含不同类型黄烷聚合物的部位。
制备例2黄烷衍生物的制备
取一定量大花或狭叶红景天黄烷聚合物部位，按照1:30的质量比，溶解在无水甲醇中，并按质量比1:0.5的比例加入相应的硫代试剂，以及质量比1:0.5的比例加入48％的HBr水溶液，在60℃条件下反应4h，反应液加入与反应液质量比5:1的蒸馏水混悬后，以乙酸乙酯进行萃取3次，合并有机层，有机层干燥后减压浓缩依次进行200-300目的硅胶柱分离、LH-20柱色谱分离，以质量分数30～70％的甲醇水溶液，高效制备液相制备得到4-位被硫代的黄烷衍生物，目前共得到51个新化合物，化合物结构式如下(表1和表2):
表1大花红景天黄烷化合物的结构与名称
表2狭叶红景天黄烷化合物的结构与名称
。
实施例14-(S)-(2,4-二氯苄硫基)-表儿茶素没食子酸酯(JP-1)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂的2,4-二氯苄硫醇，高效制备液相70％(MeOH/H2O体积比)得到化合物JP-1，淡红色粉末，收率32.1％。化合物核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z633.0386[M+H]+,calcd,633.0383)；1HNMR(500MHz,DMSO-d6)δ:7.65(1H,s,3″′-H),7.62(1H,dd,J＝8.0,1.5,5″′-H),7.41(1H,d,J＝8.0,6″′-H),6.87(1H,d,J＝1.5,2′-H),6.82(2H,s,2″,6″-H),6.72(1H,dd,J＝8.0,1.5,6′-H),6.68(1H,d,J＝8.0,5′-H),5.91(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.44(1H,s,3-H),5.27(1H,s,2-H),4.12(1H,s,4-H),4.10(2H,s,S-C-H)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),158.1(C-5),157.2(C-7),155.4(C-9),145.4(C-3″,5″),144.9(C-3′,4′),138.9(C-4″),135.4(C-2″′),134.1(C-4″′),132.4(C-6″′),132.2(C-1′),128.9(C-3″′),127.3(C-1″′,5″′),118.4(C-1″),117.5(C-6′),115.2(C-5′),114.2(C-2′),108.6(C-2″,6″),96.6(C-10),95.9(C-6),94.0(C-8),72.8(C-2),71.3(C-3),40.0(C-4),33.1(S-C).
实施例24-(S)-(4-氯苄硫基)-表儿茶素没食子酸酯(JP-2)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为4-氯苄硫醇，高效制备液相65％(MeOH/H2O体积比)得到化合物JP-2，白色粉末，收率29.8％。化合物核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z599.0782[M+H]+,calcd,599.0773)；1HNMR(500MHz,DMSO-d6)δ:7.48(2H,m,3″′,5″′-H),7.39(2H,m,2″′,6″′-H),6.86(1H,s,2′-H),6.79(2H,s,2″,6″-H),6.68(2H,m,5′,6′-H),5.92(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.44(1H,s,3-H),5.23(1H,s,2-H),4.05(2H,s,S-C-H),4.04(1H,d,J＝2.0,4-H)；13C NMR(125MHz,DMSO-d6)δ:165.1(O-C-O),158.1(C-5),157.2(C-7),155.4(C-9),145.4(C-3″,5″),144.9(C-3′,4′),138.9(C-4″),138.0(C-1″′),131.3(C-4″′),130.7(C-2″′,6″′),128.5(C-1′),128.2(C-3″′,5″′),118.5(C-1″),117.5(C-6′),115.2(C-5′),114.2(C-2′),108.6(C-2″,6″),96.9(C-10),95.9(C-6),94.0(C-8),72.7(C-2),71.2(C-3),40.0(C-4),35.0(S-C).
实施例34-(S)-(4-甲氧基苄硫基)-表儿茶素没食子酸酯(JP-3)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为4-甲氧基苄硫醇，高效制备液相60％(MeOH/H2O体积比)得到化合物JP-3，白色粉末，收率31.3％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z595.1265[M+H]+,calcd,595.1269)；1HNMR(500MHz,DMSO-d6)δ:7.37(2H,m,2″′,6″′-H),6.90(2H,m,3″′,5″′-H),6.84(1H,s,2′-H),6.79(2H,s,2″,6″-H),6.67(2H,m,5′,6′-H),5.92(1H,d,J＝2.5,8-H),5.83(1H,d,J＝2.5,6-H),5.44(1H,s,3-H),5.25(1H,s,2-H),4.08(1H,d,J＝2.0,4-H),4.00(2H,dd,J＝27.0,13.5,S-C-H),3.75(3H,s,-OCH3)；13C NMR(125MHz,DMSO-d6)δ:165.0(O-C-O),158.1(C-5),157.9(C-4″′),157.1(C-7),155.3(C-9),145.4(C-3″,5″),144.8(C-3′,4′),138.8(C-4″),130.4(C-1″′),129.9(C-2″′,6″′),128.5(C-1′),118.6(C-1″),117.4(C-6′),115.1(C-5′),114.1(C-2′),113.7(C-3″′,5″′),108.6(C-2″,6″),97.1(C-10),95.9(C-6),94.0(C-8),72.6(C-2),71.2(C-3),55.0(C-OCH3),45.6(C-4),35.2(S-C).
实施例44-(S)-(2,4,6-三甲基苄硫基)-表儿茶素没食子酸酯(JP-4)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2,4,6-三甲基苄硫醇，高效制备液相70％(MeOH/H2O体积比)得到化合物JP-4，白色粉末，收率29.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z607.1643[M+H]+,calcd,607.1646)；1H NMR(500MHz,DMSO-d6)δ:6.88(1H,d,J＝1.5,2′-H),6.86(2H,s,2″,6″-H),6.82(2H,s,3″′,5″′-H),6.79(1H,dd,J＝8.5,1.5,6′-H),6.72(1H,d,J＝1.5,5′-H),5.96(1H,d,J＝2.5,8-H),5.84(1H,d,J＝2.5,6-H),5.45(1H,s,3-H),5.33(1H,s,2-H),4.14(2H,s,4-H),4.05(1H,s,S-C-H),2.42(6H,s,2″′,6″′-CH3),2.22(3H,s,4″′-CH3)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),158.0(C-5),157.4(C-7),155.2(C-9),145.5(C-3″,5″),145.0(C-3′,4′),138.9(C-4″),136.5(C-2″′,6″′),135.9(C-1″′),130.3(C-4″′),128.7(C-3″′,5″′),128.6(C-1′),118.6(C-1″),117.5(C-6′),115.3(C-5′),114.1(C-2′),108.7(C-2″,6″),97.3(C-10),96.0(C-6),94.1(C-8),73.1(C-2),71.7(C-3),40.6(C-4),31.1(S-C),20.6(C-4″′CH3),19.1(C-2″′,6″′CH3).
实施例54-(S)-(2-氯苄硫基)-表儿茶素没食子酸酯(JP-5)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-氯苄硫醇，高效制备液相65％(MeOH/H2O体积比)得到化合物JP-5，白色粉末，收率31.5％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z599.0791[M+H]+,calcd,599.0773)；1HNMR(500MHz,DMSO-d6)δ:7.59(1H,m,3″′-H),7.48(1H,m,5″′-H),7.31(2H,m,4″′,6″′-H),6.83(1H,s,2′-H),6.80(2H,s,2″,6″-H),6.68(2H,m,5′,6′-H),5.91(1H,d,J＝2.0,8-H),5.82(1H,d,J＝2.0,6-H),5.44(1H,s,3-H),5.30(1H,s,2-H),4.15(2H,m,S-CH2),4.13(1H,s,4-H)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),158.1(C-5),157.2(C-7),155.5(C-9),145.5(C-3″,5″),144.9(C-3′),138.9(C-4′),136.0(C-4″),133.2(C-6″′,1′),131.1(C-2″′),129.5(C-1″′),128.9(C-5″′),128.5(C-3″′),127.2(C-4″′),118.5(C-1″),117.5(C-6′),115.2(C-5′),114.2(C-2′),108.6(C-2″,6″),96.8(C-10),95.9(C-6),94.0(C-8),72.8(C-2),71.2(C-3),33.7(C-4),30.7(S-C).
实施例64-(S)-(4-氟苄硫基)-表儿茶素没食子酸酯(JP-6)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为4-氟苄硫醇，高效制备液相65％(MeOH/H2O体积比)得到化合物JP-6，白色粉末，收率27.9％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z583.1065[M+H]+,calcd,583.1069)；1HNMR(500MHz,DMSO-d6)δ:7.49(2H,m,2″′,6″′H),7.48(2H,m,3″′,5″′H),7.14(1H,s,2′-H),6.83(2H,s,2″,6″-H),6.67(2H,brs,5′,6′-H),5.90(1H,d,J＝2.0,8-H),5.81(1H,d,J＝2.0,6-H),5.42(1H,s,3-H),5.21(1H,s,2-H),4.05(2H,m,S-C-H),4.01(1H,d,J＝2.0,4-H)；13C NMR(125MHz,DMSO-d6)δ:165.1(O-C-O),160.2(C-4″′),158.0(C-5),157.2(C-7),155.4(C-9),145.4(C-3″,5″),144.9(C-3′,4′),138.9(C-4″),135.0(C-1″′),130.8(C-2″′,6″′),128.5(C-1′),118.4(C-1″),117.5(C-6′),115.2(C-3″′,5″′),115.1(C-5′),114.0(C-2′),108.6(C-2″,6″),97.0(C-10),95.9(C-6),94.0(C-8),72.7(C-2),71.2(C-3),40.0(C-4),34.9(S-C).
实施例74-(S)-(2-吡嗪基乙硫基)-表儿茶素没食子酸酯(JP-7)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-吡嗪基乙硫醇，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-7，白色粉末，收率19.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z581.1232[M+H]+,calcd,581.1224)；1HNMR(500MHz,DMSO-d6)δ:8.67(1H,s,6″′-H),8.59(1H,s,3″′-H),8.51(1H,d,J＝2.0,5″′-H),6.85(1H,d,J＝1.5,2′-H),6.80(2H,s,2″,6″-H),6.74(1H,dd,J＝8.0,1.5,6′-H),6.71(1H,d,J＝8.0,5′-H),5.95(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.36(1H,s,3-H),5.21(1H,s,2-H),4.10(1H,d,J＝1.5,4-H),3.25(2H,m,2″′-CH2),3.18(2H,m,S-CH2)；13C NMR(125MHz,DMSO-d6)δ:165.3(O-C-O),158.0(C-5),157.2(C-7),155.5(C-9),155.2(C-2″′),145.4(C-3″,5″),144.9(C-3′,4′,3″′,6″′),144.1(C-5″′),142.6(C-4″),128.3(C-1′),118.4(C-1″),117.5(C-6′),115.2(C-5′),114.1(C-2′),108.6(C-2″,6″),97.3(C-10),95.9(C-6),94.0(C-8),72.7(C-2),71.8(C-3),40.0(C-4),34.7(2″′-CH2),30.1(S-C).
实施例84-(S)-(2-糠硫醇基)-表儿茶素没食子酸酯(JP-8)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂的2-糠硫醇，高效制备液相60％(MeOH/H2O体积比)得到化合物JP-8，白色粉末，收率33.2％。
化合物核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z555.0966[M+H]+,calcd,555.0956)；1HNMR(500MHz,DMSO-d6)δ:7.62(1H,dd,J＝8.0,1.5,5″′-H),6.85(1H,d,J＝1.5,2′-H),6.79(2H,s,2″,6″-H),6.73(2H,m,5′,6′-H),6.41(1H,d,J＝8.0,4″′-H),6.38(1H,d,J＝8.0,1.5,3″′-H),5.92(1H,d,J＝1.2,8-H),5.84(1H,d,J＝1.2,6-H),5.42(1H,s,3-H),5.27(1H,s,2-H),4.13(1H,d,J＝1.2,4-H),4.08(2H,s,S-C-H)；13C NMR(125MHz,DMSO-d6)δ:165.0(O-C-O),158.0(C-5),157.1(C-7),155.4(C-9),151.5(C-2″′),145.4(C-3″,5″),144.8(C-3′,4′),142.3(C-5″′),138.8(C-4″),128.5(C-1′),118.5(C-1″),117.5(C-6′),115.2(C-5′),114.1(C-2′),110.5(C-4″′),108.6(C-2″,6″),107.5(C-3″′),96.8(C-10),95.9(C-6),94.0(C-8),72.6(C-2),71.0(C-3),40.0(C-4),27.9(S-C).
实施例94-(S)-(4-甲氧基苯硫基)-表儿茶素没食子酸酯(JP-9)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为4-甲氧基苯硫酚，高效制备液相60％(MeOH/H2O体积比)得到化合物JP-9，白色粉末，收率25.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z581.1117[M+H]+,calcd,581.1112)；1HNMR(500MHz,DMSO-d6)δ:7.56(2H,d,J＝9.0,3″′,5″′-H),7.00(2H,d,J＝9.0,2″′,6″′-H),6.82(1H,d,J＝2.0,2′-H),6.72(1H,dd,J＝8.5,2.0,6′-H),6.69(2H,s,2″,6″-H),6.67(1H,d,J＝8.5,5′-H),5.98(1H,d,J＝2.0,8-H),5.86(1H,d,J＝2.0,6-H),5.57(1H,s,3-H),5.13(1H,brs,2-H),4.32(2H,d,J＝2.0,4-H),3.79(3H,s,-OCH3)；13C NMR(125MHz,DMSO-d6)δ:164.6(O-C-O),159.2(C-5),158.3(C-7),157.3(C-9),155.5(C-4″′),145.4(C-3″,5″),144.9(C-3′,4′),138.8(C-4″),134.4(C-2″′,6″′),128.5(C-1′),124.4(C-1″′),118.4(C-1″),117.4(C-6′),115.2(C-5′),114.8(C-3″′,5″′),114.0(C-2′),108.6(C-2″,6″),96.6(C-10),96.0(C-6),94.1(C-8),72.6(C-2),70.6(C-3),55.2(C-OCH3),43.3(C-4).
实施例104-(S)-(2-氨基苯硫基)-表儿茶素没食子酸酯(JP-10)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-氨基苯硫酚，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-10，白色粉末，收率27.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z588.0931[M+Na]+,calcd,588.0935)；1HNMR(500MHz,DMSO-d6)δ:7.38(1H,dd,J＝7.5,1.5,6″′-H),7.14(1H,m,4″′-H),6.88(1H,d,J＝2.0,2′-H),6.77(2H,m,6′,5″′-H),6.67(1H,d,J＝8.5,5′-H),6.66(2H,s,2″,6″-H),6.57(1H,m,3″′-H),6.03(1H,d,J＝2.5,8-H),5.89(1H,d,J＝2.5,6-H),5.71(1H,d,J＝2.5,3-H),5.15(1H,d,J＝2.5,2-H),4.19(1H,d,J＝2.5,4-H)；13C NMR(125MHz,DMSO-d6)δ:164.3(O-C-O),158.3(C-5),157.3(C-7),155.8(C-9),150.6(C-2″′),145.3(C-3″,5″),144.9(C-3′),144.8(C-4′),138.7(C-4″),136.7(C-6″′),130.6(C-1′),128.7(C-4″′),118.5(C-1″),117.4(C-6′),116.1(C-1″′),115.2(C-5′),114.4(C-5″′),114.0(C-2′),113.2(C-3″′),108.5(C-2″,6″),96.7(C-10),96.0(C-6),94.4(C-8),72.6(C-2),70.4(C-3),40.7(C-4).
实施例114-(S)-(4-氨基苯硫基)-表儿茶素没食子酸酯(JP-11)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为4-氨基苯硫酚，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-11，白色粉末，收率27.9％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z566.1132[M+H]+,calcd,566.1115)；1HNMR(500MHz,DMSO-d6)δ:7.28(2H,d,J＝8.0,2″′,6″′-H),6.82(1H,s,2′-H),6.71(1H,d,J＝8.5,6′-H),6.68(2H,s,2″,6″-H),6.65(2H,d,J＝8.5,5′-H),6.60(2H,d,J＝8.0,3″′,5″′-H),5.91(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.57(1H,s,3-H),5.15(1H,s,2-H),4.17(1H,s,4-H)；13C NMR(125MHz,DMSO-d6)δ:164.5(O-C-O),158.0(C-5),157.3(C-7),155.5(C-9),149.3(C-4″′),145.3(C-3″,5″),144.9(C-3′),144.8(C-4′),138.7(C-4″),135.5(C-2″′,6″′),128.7(C-1′),118.6(C-1″′),117.4(C-1″),117.2(C-6′),115.2(C-5′),114.4(C-3″′,5″′),114.0(C-2′),108.5(C-2″,6″),97.1(C-10),95.9(C-6),94.1(C-8),72.5(C-2),70.6(C-3),40.4(C-4).
实施例124-(S)-(4-羟基苯硫基)-表儿茶素没食子酸酯(JP-12)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为4-羟基苯硫酚，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-12，白色粉末，收率13.4％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z567.0949[M+H]+,calcd,567.0956)；1HNMR(500MHz,DMSO-d6)δ:7.45(2H,d,J＝8.5,2″′,6″′-H),6.82(1H,d,J＝1.5,2′-H),6.80(2H,d,J＝8.5,3″′,5″′-H),6.73(1H,dd,J＝8.0,1.5,6′-H),6.70(2H,s,2″,6″-H),6.67(1H,d,J＝8.0,5′-H),5.98(1H,d,J＝2.0,8-H),5.85(1H,d,J＝2.0,6-H),5.49(1H,s,3-H),5.12(1H,brs,2-H),4.27(1H,d,J＝2.0,4-H)；13C NMR(125MHz,DMSO-d6)δ:164.6(O-C-O),158.2(C-5),157.7(C-7),157.3(C-9),155.5(C-4″′),145.4(C-3″,5″),144.9(C-3′,4′),138.7(C-4″),135.2(C-2″′,6″′),128.6(C-1′),122.1(C-1″′),118.5(C-1″),117.4(C-6′),116.2(C-3″′,5″′),115.2(C-5′),114.0(C-2′),108.6(C-2″,6″),96.8(C-10),96.0(C-6),94.1(C-8),72.6(C-2),70.5(C-3),43.5(C-4).
实施例134-(S)-(3-甲氧基苯硫基)-表儿茶素没食子酸酯(JP-13)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为3-甲氧基苯硫酚，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-13，白色粉末，收率23.5％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z581.1123[M+H]+,calcd,581.1112)；1HNMR(500MHz,DMSO-d6)δ:7.31(1H,m,5″′-H),7.19(1H,d,J＝2.5,2″′-H),7.14(1H,dd,J＝9.0,2.5,6″′-H),6.86(1H,dd,J＝9.0,2.5,4″′-H),6.79(1H,d,J＝2.5,2′-H),6.76(2H,s,2″,6″-H),6.71(1H,dd,J＝9.0,2.5,6′-H),6.65(1H,d,J＝9.0,5′-H),5.99(1H,d,J＝2.5,8-H),5.88(1H,d,J＝2.5,6-H),5.54(1H,d,J＝2.5,3-H),5.18(1H,d,J＝2.5,2-H),4.59(1H,d,J＝2.5,4-H),3.81(3H,s,-OCH3)；13C NMR(125MHz,DMSO-d6)δ:164.9(O-C-O),159.7(C-3″′),158.4(C-5),157.3(C-7),155.6(C-9),145.4(C-3″,5″),145.0(C-3′),144.9(C-4′),138.9(C-4″),136.2(C-1″′),130.0(C-1′),128.4(C-5″′),121.7(C-6″′),118.4(C-1″),117.5(C-6′),115.3(C-5′),114.4(C-2′),114.0(C-2″′),112.9(C-4″′),108.7(C-2″,6″),96.0(C-10),95.9(C-6),94.2(C-8),72.8(C-2),70.9(C-3),55.2(C-OCH3),41.2(C-4).
实施例144-(S)-(3,4-二甲氧基苯硫基)-表儿茶素没食子酸酯(JP-14)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为3,4-二甲氧基苯硫酚，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-14，白色粉末，收率28.6％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z611.1208[M+H]+,calcd,611.1218)；1HNMR(500MHz,DMSO-d6)δ:7.17(1H,dd,J＝9.0,2.5,6″′-H),7.16(1H,d,J＝2.5,2″′-H),7.15(1H,d,J＝9.0,5″′-H),6.80(1H,d,J＝2.5,2′-H),6.72(2H,s,2″,6″-H),6.71(1H,dd,J＝9.0,2.5,6′-H),6.65(1H,d,J＝9.0,5′-H),5.99(1H,d,J＝2.5,8-H),5.85(1H,d,J＝2.5,6-H),5.52(1H,brs,3-H),5.16(1H,brs,2-H),4.43(1H,d,J＝2.5,4-H),3.80(3H,s,4″′-OCH3),3.78(3H,s,3″′-OCH3)；13C NMR(125MHz,DMSO-d6)δ:164.7(O-C-O),158.3(C-5),157.3(C-7),155.6(C-9),148.9(C-4″′),148.7(C-3″′),145.4(C-3″,5″),144.9(C-3′),144.8(C-4′),138.8(C-4″),128.5(C-1′),124.9(C-1″′),124.7(C-6″′),118.4(C-1″),117.4(C-6′),115.6(C-5′),115.2(C-2′),114.0(C-5″′),112.1(C-2″′),108.6(C-2″,6″),96.5(C-10),95.9(C-6),94.2(C-8),72.6(C-2),70.8(C-3),55.5(C-4″′-OCH3),55.4(C-3″′-OCH3),42.6(C-4).
实施例154-(S)-(3-氨基苯硫基)-表儿茶素没食子酸酯(JP-15)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为3-氨基苯硫酚，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-15，白色粉末，收率19.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z588.0941[M+H]+,calcd,588.0935)；1HNMR(500MHz,DMSO-d6)δ:7.04(1H,m,2″′-H),6.79(2H,m,5″′,6″′-H),6.77(1H,d,J＝2.5,2′-H),6.71(2H,s,2″,6″-H),6.68(1H,dd,J＝9.0,2.5,6′-H),6.65(1H,d,J＝9.0,5′-H),6.50(1H,dd,J＝9.0,2.5,4″′-H),5.98(1H,brs,8-H),5.86(1H,brs,6-H),5.58(1H,brs,3-H),5.18(1H,brs,2-H),4.48(1H,brs,4-H)；13C NMR(125MHz,DMSO-d6)δ:164.6(O-C-O),158.3(C-5),157.3(C-7),155.6(C-9),149.3(C-3″′),145.4(C-3″,5″),144.9(C-3′,4′),134.4(C-4″),129.6(C-1″′),129.5(C-1′),128.5(C-5″′),117.7(C-1″),117.4(C-6′),115.6(C-6″′),115.2(C-5′),114.0(C-2′),113.0(C-2″′),111.3(C-4″′),108.6(C-2″,6″),96.4(C-10),95.9(C-6),94.1(C-8),72.8(C-2),70.6(C-3),41.4(C-4).
实施例164-(S)-(2-甲氧基苯硫基)-表儿茶素没食子酸酯(JP-16)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-甲氧基苯硫酚，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-16，白色粉末，收率29.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z581.1118[M+H]+,calcd,581.1112)；1HNMR(500MHz,DMSO-d6)δ:7.70(1H,dd,J＝8.0,1.5,6″′-H),7.30(1H,m,4″′-H),7.06(1H,dd,J＝8.0,1.5,3″′-H),7.01(1H,m,5″′-H),6.76(1H,d,J＝2.0,2′-H),6.74(2H,s,2″,6″-H),6.68(1H,dd,J＝8.0,2.0,6′-H),6.50(1H,d,J＝8.0,5′-H),5.98(1H,d,J＝2.0,8-H),5.88(1H,d,J＝2.0,6-H),5.62(1H,brs,3-H),5.14(1H,brs,2-H),4.56(1H,d,J＝2.0,4-H),3.84(3H,s,-OCH3)；13C NMR(125MHz,DMSO-d6)δ:164.8(O-C-O),158.3(C-5),157.4(C-7),155.7(C-9),145.4(C-3″,5″),144.9(C-3′,4′),138.8(C-4″),131.1(C-1′),128.5(C-6″′),128.4(C-4″′),122.5(C-1″),121.1(C-5″′),118.5(C-1″′),117.4(C-6′),115.2(C-5′),114.0(C-2′),111.4(C-3″′),108.7(C-2″,6″),96.3(C-10),96.0(C-6),94.2(C-8),72.9(C-2),70.4(C-3),55.8(C-OCH3),40.4(C-4).
实施例174-(S)-(1-丁硫基)-表儿茶素没食子酸酯(JP-17)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为1-丁硫醇，高效制备液相70％(MeOH/H2O体积比)得到化合物JP-17，白色粉末。收率15.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z531.1324[M+H]+,calcd,531.1319)；1HNMR(500MHz,DMSO-d6)δ:6.86(1H,d,J＝1.5,2′-H),6.79(2H,s,2″,6″-H),6.77(1H,dd,J＝8.5,1.5,6′-H),6.70(1H,d,J＝8.5,5′-H),5.94(1H,d,J＝2.0,8-H),5.84(1H,d,J＝2.0,6-H),5.44(1H,s,3-H),5.18(1H,s,2-H),4.00(1H,d,J＝2.0,4-H),2.82(1H,s,1″′-H),1.70(2H,m,2″′-H),1.48(2H,m,3″′-H),0.94(3H,t,4″′-H)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),157.8(C-5),157.2(C-7),155.2(C-9),145.4(C-3″,5″),144.9(C-3′,4′),138.8(C-4″),128.6(C-1′),118.5(C-1″),117.5(C-6′),115.3(C-5′),114.1(C-2′),108.6(C-2″,6″),97.6(C-10),95.9(C-6),94.0(C-8),72.7(C-2),71.8(C-3),40.0(C-4),31.4(C-1″′,2″′),21.2(C-3″′),13.5(C-4″′).
实施例184-(S)-(1-烯丙基硫基)-表儿茶素没食子酸酯(JP-18)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为1-烯丙基硫醇，高效制备液相65％(MeOH/H2O体积比)得到化合物JP-18，白色粉末，收率17.6％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z515.1019[M+H]+,calcd,515.1006)；1HNMR(500MHz,DMSO-d6)δ:6.86(1H,d,J＝1.5,2′-H),6.79(2H,s,2″,6″-H),6.77(1H,dd,J＝8.5,1.5,6′-H),6.70(1H,d,J＝8.5,5′-H),5.98(1H,m,2″′-H),5.94(1H,d,J＝2.0,8-H),5.84(1H,d,J＝2.0,6-H),5.45(1H,s,3-H),5.30(1H,d,J＝18.0,3″′-H),5.25(1H,s,2-H),5.11(1H,d,J＝10.5,3″′-H),4.02(1H,d,J＝2.0,4-H),3.49(2H,m,1″′-H)；13C NMR(125MHz,DMSO-d6)δ:165.5(O-C-O),158.5(C-5),157.7(C-7),155.9(C-9),145.9(C-3″,5″),145.4(C-3′,4′),139.4(C-4″),135.2(C-2″′),129.1(C-1′),119.0(C-1″),118.0(C-3″′),117.7(C-6′),115.7(C-5′),114.6(C-2′),109.1(C-2″,6″),97.7(C-10),96.4(C-6),94.6(C-8),73.3(C-2),71.7(C-3),39.1(C-4),35.1(C-1″′).
实施例194-(S)-(3-甲基-2-(R)-丁硫基)-表儿茶素没食子酸酯(JP-19)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为3-甲基2-丁硫醇，高效制备液相45％(CH3CN/H2O体积比)得到化合物JP-19，白色粉末，收率9.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z545.1476[M+H]+,calcd,545.1476)；1HNMR(500MHz,DMSO-d6)δ:6.84(1H,d,J＝2.0,2′-H),6.77(2H,s,2″,6″-H),6.75(1H,dd,J＝8.0,2.0,6′-H),6.74(1H,dd,J＝8.0,5′-H),5.93(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.46(1H,s,3-H),5.12(1H,s,2-H),3.97(1H,d,J＝2.0,4-H),3.09(1H,m,2″′-H),1.89(1H,m,3″′-H),1.41(3H,d,J＝7.0,1″′-H),1.03(3H,d,J＝6.5,3″′-CH3),0.96(3H,d,J＝6.5,3″′-CH3)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),157.8(C-5),157.1(C-7),155.2(C-9),145.4(C-3″,5″),144.9(C-3′,4′),138.9(C-4″),128.7(C-1′),118.5(C-1″),117.4(C-6′),115.3(C-5′),114.0(C-2′),108.6(C-2″,6″),97.7(C-10),95.9(C-6),94.0(C-8),72.8(C-2),72.0(C-3),47.7(C-2″′),38.1(C-4),32.6(C-3″′),19.5(C-1″′),19.2(C-3″′-CH3),19.0(C-3″′-CH3).
实施例204-(S)-(3-甲基-2-(S)-丁硫基)-表儿茶素没食子酸酯(JP-20)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为3-甲基-2-丁硫醇，高效制备液相45％(CH3CN/H2O体积比)得到化合物JP-20，白色粉末，收率11.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z545.1486[M+H]+,calcd,545.1476)；1HNMR(500MHz,DMSO-d6)δ:6.82(1H,d,J＝2.0,2′-H),6.74(2H,s,2″,6″-H),6.72(1H,dd,J＝8.0,2.0,6′-H),6.66(1H,dd,J＝8.0,5′-H),5.89(1H,d,J＝2.0,8-H),5.79(1H,d,J＝2.0,6-H),5.43(1H,s,3-H),5.11(1H,s,2-H),3.98(1H,d,J＝2.0,4-H),3.14(1H,m,2″′-H),2.00(1H,m,3″′-H),1.28(3H,d,J＝6.5,1″′-H),1.00(3H,d,J＝6.5,3″′-CH3),0.94(3H,d,J＝6.5,3″′-CH3)；13C NMR(125MHz,DMSO-d6)δ:165.3(O-C-O),157.8(C-5),157.3(C-7),155.2(C-9),145.5(C-3″,5″),145.0(C-3′),144.9(C-4′),138.9(C-4″),128.7(C-1′),118.5(C-1″),117.4(C-6′),115.3(C-5′),114.0(C-2′),108.7(C-2″,6″),97.8(C-10),96.0(C-6),94.0(C-8),72.6(C-2),72.4(C-3),47.5(C-2″′),40.4(C-4),32.7(C-3″′),19.3(C-1″′),18.9(C-3″′-CH3),18.5(C-3″′-CH3).
实施例214-(S)-(环戊硫基)-表儿茶素没食子酸酯(JP-21)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为环戊硫醇，高效制备液相70％(MeOH/H2O体积比)得到化合物JP-21，白色粉末，收率15.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z543.1323[M+H]+,calcd,543.1319)；1HNMR(500MHz,DMSO-d6)δ:6.85(1H,s,2′-H),6.76(2H,m,2″,6″-H),6.75(1H,dd,J＝8.0,2.0,6′-H),6.68(1H,d,J＝8.0,5′-H),5.92(1H,d,J＝2.0,8-H),5.81(1H,d,J＝2.0,6-H),5.41(1H,s,3-H),5.21(1H,s,2-H),4.02(1H,s,4-H),3.44(1H,m,1″′-H),2.10(2H,m,2″′,5″′-H),1.73(2H,m,2″′,5″′-H),1.58(4H,m,3″′,4″′-H)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),157.8(C-5),157.0(C-7),155.1(C-9),145.4(C-3″,5″),144.9(C-3′,4′),138.9(C-4″),128.7(C-1′),118.5(C-1″),117.5(C-6′),115.3(C-5′),114.0(C-2′),108.6(C-2″,6″),97.8(C-10),95.9(C-6),94.0(C-8),72.8(C-2),72.0(C-3),44.2(C-4),40.0(S-C),33.8(C-2″′),33.5(C-5″′)24.6(C-3″′)24.2(C-4″′).
实施例224-(S)-(1-甲氧基-1-氧代-2-(S)-丙硫基)-表儿茶素没食子酸酯(JP-22)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-巯基丙酸，高效制备液相40％(CH3CN/H2O体积比)得到化合物JP-22，白色粉末，收率15.1％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z561.1065[M+H]+,calcd,561.1061)；1HNMR(500MHz,DMSO-d6)δ:6.84(1H,d,J＝2.0,2′-H),6.78(2H,m,2″,6″-H),6.75(1H,dd,J＝8.0,2.0,6′-H),6.69(1H,d,J＝8.0,5′-H),5.95(1H,d,J＝2.5,8-H),5.84(1H,d,J＝2.5,6-H),5.33(1H,s,3-H),5.30(1H,s,2-H),4.17(1H,d,J＝2.0,4-H),3.91(1H,dd,J＝14.0,7.0,S-C-H),3.72(3H,s,-O-C-O-CH3),1.55(3H,d,J＝7.0,-C-CH3)；13C NMR(125MHz,DMSO-d6)δ:173.0(-COOCH3),165.0(O-C-O),158.2(C-5),157.2(C-7),155.2(C-9),145.5(C-3″,5″),145.0(C-3′),144.9(C-4′),138.9(C-4″),128.5(C-1′),118.5(C-1″),117.5(C-6′),115.3(C-5′),114.1(C-2′),108.6(C-2″,6″),97.1(C-10),96.0(C-6),94.1(C-8),72.8(C-2),71.8(C-3),52.3(C-OCH3),42.4(S-C),40.0(C-4),18.3(C-CH3).
实施例234-(S)-(1-甲氧基-1-氧代-2-(R)-丙硫基)-表儿茶素没食子酸酯(JP-23)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-巯基丙酸，高效制备液相40％(CH3CN/H2O体积比)得到化合物JP-23，白色粉末，收率13.4％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z561.107[M+H]+,calcd,561.1075)；1HNMR(500MHz,DMSO-d6)δ:6.86(1H,d,J＝2.0,2′-H),6.79(2H,m,2″,6″-H),6.76(1H,dd,J＝8.0,2.0,6′-H),6.69(1H,d,J＝8.0,5′H),5.94(1H,d,J＝2.5,8-H),5.84(1H,d,J＝2.5,6-H),5.39(1H,s,3-H),5.23(1H,s,2-H),4.26(1H,d,J＝2.0,4-H),3.84(1H,dd,J＝14.0,7.0,S-C-H),3.69(3H,s,-O-C-O-CH3),1.48(3H,d,J＝7.0,-C-CH3)；13C NMR(125MHz,DMSO-d6)δ:173.0(-COOCH3),164.9(O-C-O),158.2(C-5),157.2(C-7),155.5(C-9),145.5(C-3″,5″),145.0(C-3′),144.9(C-4′),138.9(C-4″),128.5(C-1′),118.5(C-1″),117.5(C-6′),115.3(C-5′),114.1(C-2′),108.7(C-2″,6″),96.4(C-10),95.9(C-6),94.1(C-8),72.9(C-2),71.6(C-3),52.1(C-OCH3),40.9(S-C),40.0(C-4),17.5(C-CH3).
实施例244-(S)-(2-甲氧基-2-氧代乙硫基)-表儿茶素没食子酸酯(JP-24)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-巯基乙酸，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-24，白色粉末，收率27.9％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z547.0913[M+H]+,calcd,547.0905)；1HNMR(500MHz,DMSO-d6)δ:6.88(1H,d,J＝1.5,2′-H),6.78(2H,s,2″,6″-H),6.77(1H,dd,J＝8.0,1.5,6′-H),6.69(1H,d,J＝8.0,5′-H),5.95(1H,d,J＝2.5,8-H),5.85(1H,d,J＝2.5,6-H),5.44(1H,s,3-H),5.27(1H,s,2-H),4.14(1H,d,J＝2.0,4-H),3.68(3H,s,-O-C-O-CH3),3.67(2H,m,S-C-H)；13C NMR(125MHz,DMSO-d6)δ:171.2(O-C-OCH3),165.5(O-C-O),158.8(C-5),157.8(C-7),155.9(C-9),145.9(C-3″,5″),145.4(C-3′,4′),139.3(C-4″),129.0(C-1′),119.0(C-1″),118.1(C-6′),115.7(C-5′),114.7(C-2′),109.1(C-2″,6″),97.1(C-10),96.4(C-6),94.6(C-8),73.1(C-2),71.5(C-3),52.7(C-OCH3),40.8(C-4),34.2(S-C).
实施例254-(S)-(2-丁氧基-2-氧代乙硫基)-表儿茶素没食子酸酯(JP-25)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-巯基乙酸，反应溶剂为正丁醇，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-25，白色粉末，收率29.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z589.1386[M+H]+,calcd,589.1388)；1HNMR(500MHz,DMSO-d6)δ:6.88(1H,d,J＝2.0,2′-H),6.78(2H,s,2″,6″-H),6.77(1H,dd,J＝8.0,1.5,6′-H),6.69(1H,d,J＝8.0,5′-H),5.95(1H,d,J＝2.0,8-H),5.85(1H,d,J＝2.0,6-H),5.44(1H,s,3-H),5.28(1H,s,2-H),4.17(1H,d,J＝2.0,4-H),4.10(2H,m,1″′-H),3.65(2H,m,S-C-H),1.57(2H,m,2″′-H),1.32(2H,m,3″′-H),0.85(3H,t,4″′-H)；13C NMR(125MHz,DMSO-d6)δ:170.7(O-C-OCH2),165.4(O-C-O),158.8(C-5),157.9(C-7),156.0(C-9),145.9(C-3″,5″),145.4(C-3′,4′),139.3(C-4″),129.0(C-1′),119.0(C-1″),118.1(C-6′),115.7(C-5′),114.7(C-2′),109.1(C-2″,6″),97.1(C-10),96.4(C-6),94.5(C-8),73.1(C-2),71.4(C-3),65.1(C-1″′),40.0(C-4),34.2(S-C),30.5(C-2″′),19.0(C-3″′),14.0(C-4″′).
实施例264-(S)-(2-乙氧基-2-氧代乙硫基)-表儿茶素没食子酸酯(JP-26)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-巯基乙酸，所用反应溶剂为无水乙醇，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-26，白色粉末，收率27.6％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z561.1064[M+H]+,calcd,561.1061)；1HNMR(500MHz,DMSO-d6)δ:6.87(1H,s,2′-H),6.77(2H,s,2″,6″-H),6.76(1H,dd,J＝8.0,1.5,6′-H),6.69(1H,d,J＝8.0,5′-H),5.95(1H,d,J＝2.5,8-H),5.84(1H,d,J＝2.5,6-H),5.44(1H,s,3-H),5.27(1H,s,2-H),4.14(2H,m,S-C-H),4.11(1H,brs,4-H),3.64(3H,m,-O-CH2),1.20(3H,t,H-CH3)；13C NMR(125MHz,DMSO-d6)δ:170.2(O-C-OCH2),164.9(O-C-O),158.3(C-5),157.4(C-7),155.4(C-9),145.4(C-3″,5″),144.9(C-3′,4′),138.8(C-4″),129.7(C-1′),118.5(C-1″),117.6(C-6′),115.2(C-5′),114.2(C-2′),109.1(C-2″,6″),96.6(C-10),95.9(C-6),94.1(C-8),72.6(C-2),70.9(C-3),61.0(C-OCH2),33.9(C-4),33.5(S-C),14.0(C-CH3).
实施例274-(S)-(4-氯苄硫基)-表没食子儿茶素没食子酸酯(JP-27)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为4-氯苄硫醇，高效制备液相60％(MeOH/H2O体积比)得到化合物JP-27，白色粉末，收率30.9％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z615.0727[M+H]+,calcd,615.0722)；1HNMR(500MHz,DMSO-d6)δ:7.48(2H,d,J＝8.5,3″′,5″′-H),7.39(2H,d,J＝8.5,2″′,6″′-H),6.79(2H,s,2″,6″-H),6.41(2H,s,2′,6′-H),5.91(1H,d,J＝2.5,8-H),5.83(1H,d,J＝2.5,6-H),5.36(1H,s,3-H),5.26(1H,s,2-H),4.07(2H,m,S-CH2),4.00(1H,s,4-H)；13C NMR(125MHz,DMSO-d6)δ:165.7(O-C-O),158.5(C-5),157.7(C-7),155.9(C-9),146.3(C-3′,5′),145.9(C-3″,5″),139.4(C-4″),138.2(C-1″′),133.1(C-4′),131.9(C-4″′),131.2(C-2″′,6″′),128.7(C-3″′,5″′),128.3(C-1′),119.1(C-1″),109.2(C-2″,6″),105.9(C-2′,6′),97.5(C-10),96.4(C-6),94.5(C-8),73.3(C-2),71.7(C-3),40.0(C-4),35.4(S-C).
实施例284-(S)-(4-甲氧基苄硫基)-表没食子儿茶素没食子酸酯(JP-28)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为4-甲氧基苄硫醇，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-28，白色粉末，收率29.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z611.1214[M+H]+,calcd,611.1218)；1HNMR(500MHz,DMSO-d6)δ:7.36(2H,d,J＝8.5,2″′,6″′-H),6.88(2H,d,J＝8.5,3″′,5″′-H),6.79(2H,s,2″,6″-H),6.40(2H,s,2′,6′-H),5.92(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.37(1H,s,3-H),5.29(1H,s,2-H),4.03(2H,d,J＝2.0,4-H),4.01(2H,m,S-CH2),3.75(3H,s,-OCH3)；13C NMR(125MHz,DMSO-d6)δ:165.6(O-C-O),158.7(C-5),158.5(C-4″′),157.7(C-7),155.9(C-9),146.3(C-3′,5′),145.9(C-3″,5″),139.4(C-4″),133.0(C-4′),130.7(C-1″′),130.5(C-2″′,6″′),128.4(C-1′),119.2(C-1″),114.2(C-3″′,5″′),109.2(C-2″,6″),105.9(C-2′,6′),97.7(C-10),96.4(C-6),94.5(C-8),73.3(C-2),71.7(C-3),55.5(C-OCH3),40.0(C-4),35.7(S-C).
实施例294-(S)-(2,4-二氯苄硫基)-表没食子儿茶素没食子酸酯(JP-29)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2,4-二氯苄硫醇，高效制备液相65％(MeOH/H2O体积比)得到化合物JP-29，白色粉末，收率30.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z649.0337[M+H]+,calcd,649.0333)；1HNMR(500MHz,DMSO-d6)δ:7.65(1H,d,J＝2.5,3″′-H),7.62(1H,dd,J＝8.5,2.5,5″′-H),7.41(1H,d,J＝8.5,6″′-H),6.80(2H,s,2″,6″-H),6.41(2H,s,2′,6′-H),5.91(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.36(1H,s,3-H),5.30(1H,s,2-H),4.13(2H,m,S-CH2),4.05(1H,d,J＝2.0,4-H)；13C NMR(125MHz,DMSO-d6)δ:165.8(O-C-O),158.6(C-5),157.7(C-7),155.9(C-9),146.3(C-3′,5′),145.9(C-3″,5″),139.4(C-4″),135.7(C-2″′),134.6(C-4″′),133.1(C-6″′),132.9(C-4′),132.7(C-1′),129.5(C-3″′),128.3(C-1″′),127.8(C-5″′),119.1(C-1″),109.2(C-2″,6″),105.9(C-2′,6′),97.3(C-10),96.4(C-6),94.5(C-8),73.4(C-2),71.7(C-3),40.9(C-4),33.5(S-C).
实施例304-(S)-(2,4,6-三甲基苄硫基)-表没食子儿茶素没食子酸酯(JP-30)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2,4,6-三甲氧基苄硫醇，高效制备液相65％(MeOH/H2O体积比)得到化合物JP-30，白色粉末，收率27.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z623.1583[M+H]+,calcd,623.1582)；1H NMR(500MHz,DMSO-d6)δ:6.85(2H,s,3″′,5″′-H),6.80(2H,s,2″,6″-H),6.43(2H,s,2′,6′-H),5.95(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.35(2H,s,3,2-H),4.11(1H,s,4-H),4.09(2H,s,S-CH2),2.42(6H,s,2″′,6″′-CH3),2.20(3H,s,4″′-CH3)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),158.0(C-5),157.3(C-7),155.2(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.9(C-4″),136.5(C-2″′,6″′),135.9(C-1″′),132.6(C-4″′),130.2(C-4′),128.7(C-3″′,5″′),127.9(C-1′),118.6(C-1″),108.7(C-2″,6″),105.3(C-2′,6′),97.3(C-10),96.0(C-6),94.0(C-8),73.0(C-2),71.6(C-3),40.7(C-4),31.0(S-C),20.5(4″′-CH3),19.1(2″′,6″′-CH3).
实施例314-(S)-(2-氯苄硫基)-表没食子儿茶素没食子酸酯(JP-31)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2-氯苄硫醇，高效制备液相60％(MeOH/H2O体积比)得到化合物JP-31，白色粉末，收率29.8％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z615.0736[M+H]+,calcd,615.0722)；1HNMR(500MHz,DMSO-d6)δ:7.59(1H,m,3″′-H),7.47(1H,m,5″′-H),7.31(2H,m,4″′,6″′-H),6.79(2H,s,2″,6″-H),6.39(2H,s,2′,6′-H),5.90(1H,d,J＝2.0,8-H),5.82(1H,d,J＝2.0,6-H),5.36(1H,s,3-H),5.33(1H,s,2-H),4.14(2H,m,S-CH2),4.10(1H,s,4-H)；13C NMR(125MHz,DMSO-d6)δ:165.3(O-C-O),158.1(C-5),157.3(C-7),155.5(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.9(C-4″),135.9(C-4′),133.2(C-6″′),132.6(C-1′),131.1(C-2″′),129.5(C-1″′),128.9(C-5″′),127.8(C-3″′),127.2(C-4″′),118.6(C-1″),108.6(C-2″,6″),105.4(C-2′,6′),96.8(C-10),95.9(C-6),94.0(C-8),72.8(C-2),71.2(C-3),33.7(C-4),30.7(S-C).
实施例324-(S)-(4-氟苄硫基)-表没食子儿茶素没食子酸酯(JP-32)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为4-氟苄硫醇，高效制备液相60％(MeOH/H2O体积比)得到化合物JP-32，白色粉末，收率28.3％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z599.1012[M+H]+,calcd,599.1018)；1HNMR(500MHz,DMSO-d6)δ:7.48(2H,t,2″′,6″′-H),7.14(2H,t,J＝8.5,3″′,5″′-H),6.78(2H,s,2″,6″-H),6.39(1H,s,2′,6′-H),5.90(1H,d,J＝2.0,8-H),5.82(1H,d,J＝2.0,6-H),5.35(1H,s,3-H),5.25(1H,brs,2-H),4.06(2H,m,S-CH2),4.02(1H,m,4-H)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),162.1(C-4″′),160.2(C-5),158.0(C-7),157.2(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.9(C-4″),134.8(C-1″′),132.5(C-4′),130.8(C-2″′,6″′),127.8(C-1′),118.6(C-1″),115.1(C-3″′,5″′),108.7(C-2″,6″),105.4(C-2′,6′),97.1(C-10),95.9(C-6),94.0(C-8),72.8(C-2),71.2(C-3),40.0(C-4),34.9(C-CH2).
实施例334-(S)-(2-糠硫醇基)-表没食子儿茶素没食子酸酯(JP-33)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2-糠硫醇，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-33，白色粉末，收率29.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z571.0905[M+H]+,calcd,571.0905)；1HNMR(500MHz,DMSO-d6)δ:7.60(1H,s,5″′-H),6.78(2H,s,2″,6″-H),6.39(2H,s,2′,6′-H),6.38(2H,m,3″′,4″′-H),5.91(1H,d,J＝1.8,8-H),5.82(1H,d,J＝1.8,6-H),5.33(1H,s,3-H),5.28(1H,s,2-H),4.09(1H,d,J＝1.2,4-H),4.05(2H,m,S-C-H)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),158.1(C-5),157.2(C-7),155.5(C-9),151.5(C-2″′),145.8(C-3′,5′),142.4(C-3″,5″),138.9(C-5″′),132.5(C-4″),127.8(C-1′),118.6(C-1″),110.6(C-4″′),108.7(C-2″,6″),107.6(C-2′,6′),105.4(C-3″′),96.9(C-10),95.9(C-6),94.0(C-8),72.7(C-2),71.0(C-3),40.0(C-4),27.9(S-C).
实施例344-(S)-(2-吡嗪基乙硫基)-表没食子儿茶素没食子酸酯(JP-34)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2-吡嗪基乙硫醇，高效制备液相45％(MeOH/H2O体积比)得到化合物JP-34，白色粉末，收率11.4％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z597.1171[M+H]+,calcd,597.1174)；1HNMR(500MHz,DMSO-d6)δ:8.67(1H,s,6″′-H),8.59(1H,s,3″′-H),8.51(1H,d,J＝2.0,5″′-H),6.79(2H,s,2″,6″-H),6.40(2H,s,2′,6′-H),5.94(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.29(1H,s,3-H),5.24(1H,s,2-H),4.07(1H,d,J＝1.5,4-H),3.25(2H,m,2″′-CH2),3.18(2H,m,S-C-H)；13C NMR(125MHz,DMSO-d6)δ:165.3(O-C-O),158.0(C-5),157.2(C-7),155.4(C-9),155.2(C-2″′),145.8(C-3′,5′),145.4(C-3″,5″),144.9(C-3″′),144.1(C-6″′),142.6(C-5″′),138.9(C-4″),132.3(C-4′),127.8(C-1′),118.6(C-1″),108.7(C-2″,6″),105.3(C-2′,6′),97.4(C-10),95.9(C-6),94.0(C-8),72.7(C-2),71.7(C-3),40.0(C-4),34.7(2″′-CH2),30.1(S-C).
实施例354-(S)-(4-甲氧基苯硫基)-表没食子儿茶素没食子酸酯(JP-35)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为4-甲氧基苯硫醇，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-35，白色粉末，收率29.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z597.1072[M+H]+,calcd,597.1061)；1HNMR(500MHz,DMSO-d6)δ:7.56(2H,d,J＝8.5,3″′,5″′-H),7.02(2H,d,J＝8.5,2″′,6″′-H),6.70(2H,s,2″,6″-H),6.38(2H,s,2′,6′-H),5.99(1H,d,J＝2.5,8-H),5.87(1H,d,J＝2.5,6-H),5.51(1H,s,3-H),5.17(1H,s,2-H),4.32(1H,d,J＝2.0,4-H),3.81(3H,s,-OCH3)；13CNMR(125MHz,DMSO-d6)δ:164.6(O-C-O),159.2(C-5),158.3(C-7),157.3(C-9),155.5(C-4″′),145.8(C-3′,5′),145.3(C-3″,5″),138.8(C-4″),134.2(C-2″′,6″′),132.5(C-4′),127.8(C-1′),124.5(C-1″′),118.5(C-1″),114.9(C-3″′,5″′),108.7(C-2″,6″),105.2(C-2′,6′),96.7(C-10),96.0(C-6),94.1(C-8),72.6(C-2),70.5(C-3),55.2(C-OCH3),43.4(S-C).
实施例364-(S)-(2-氨基苯硫基)-表没食子儿茶素没食子酸酯(JP-36)的制备
制备方法同制备例2，所用黄烷聚合物原料为大花红景天50％部位，所用硫代试剂为2-氨基苯硫酚，高效制备液相55％(MeOH/H2O体积比)得到化合物JP-36，白色粉末，收率21.3％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z604.0887[M+H]+,calcd,604.0884)；1HNMR(500MHz,DMSO-d6)δ:7.35(1H,d,J＝7.5,6″′-H),7.14(1H,m,4″′-H),6.76(1H,d,J＝7.5,5″′-H),6.63(2H,s,2″,6″-H),6.57(1H,m,3″′-H),6.42(2H,s,2′,6′-H),6.01(1H,d,J＝1.0,8-H),5.88(1H,d,J＝1.0,6-H),5.61(1H,s,3-H),5.16(1H,s,2-H),4.16(1H,s,4-H)；13C NMR(125MHz,DMSO-d6)δ:164.2(O-C-O),158.3(C-5),157.3(C-7),155.8(C-9),150.6(C-2″′),145.8(C-3′,5′),145.3(C-3″,5″),138.7(C-4″),136.6(C-6″′),132.4(C-4′),130.6(C-1′),127.9(C-4″′),118.6(C-1″),116.0(C-1″′),114.4(C-5″′),113.2(C-3″′),108.6(C-2″,6″),105.2(C-2′,6′),96.8(C-10),96.0(C-6),94.4(C-8),72.6(C-2),70.4(C-3),40.7(C-4).
实施例374-(S)-(4-氨基苯硫基)-表没食子儿茶素没食子酸酯(JP-37)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为4-氨基苯硫酚，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-37，白色粉末，收率28.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z582.1072[M+H]+,calcd,582.1065)；1HNMR(500MHz,DMSO-d6)δ:7.25(2H,d,J＝8.0,2″′,6″′-H),6.67(2H,s,2″,6″-H),6.58(2H,d,J＝8.0,3″′,5″′-H),6.37(2H,s,2′,6′-H),5.96(1H,d,J＝2.0,8-H),5.83(1H,d,J＝2.0,6-H),5.50(1H,s,3-H),5.19(1H,s,2-H),4.14(1H,s,4-H)；13C NMR(125MHz,DMSO-d6)δ:164.5(O-C-O),158.0(C-5),157.3(C-7),155.5(C-9),149.3(C-4″′),145.8(C-3′,5′),145.3(C-3″,5″),138.7(C-4″),135.4(C-2″′,6″′),132.4(C-4′),128.0(C-1′),118.7(C-1″′),117.3(C-1″),114.4(C-3″′,5″′),108.6(C-2″,6″),105.2(C-2′,6′),97.2(C-10),95.9(C-6),94.1(C-8),72.5(C-2),70.5(C-3),44.0(C-4).
实施例384-(S)-(4-羟基苯硫基)-表没食子儿茶素没食子酸酯(JP-38)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为4-羟基苯硫酚，高效制备液相45％(MeOH/H2O体积比)得到化合物JP-38，白色粉末，收率16.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z583.0884[M+H]+,calcd,583.0905)；1HNMR(500MHz,DMSO-d6)δ:7.44(2H,d,J＝8.5,2″′,6″′-H),6.82(2H,d,J＝8.5,3″′,5″′-H),6.67(2H,s,2″,6″-H),6.37(1H,s,2′,6′-H),5.97(1H,d,J＝2.0,8-H),5.85(1H,d,J＝2.0,6-H),5.49(1H,s,3-H),5.16(1H,brs,2-H),4.24(1H,d,J＝2.0,4-H)；13C NMR(125MHz,DMSO-d6)δ:164.6(O-C-O),158.2(C-5),157.7(C-7),157.3(C-9),155.5(C-4″′),145.8(C-3′,5′),145.3(C-3″,5″),138.7(C-4″),135.0(C-2″′,6″′),132.5(C-4′),127.9(C-1′),122.1(C-1″′),118.6(C-1″),116.3(C-3″′,5″′),108.6(C-2″,6″),105.2(C-2′,6′),96.8(C-10),95.9(C-6),94.1(C-8),72.5(C-2),70.5(C-3),43.7(C-4).
实施例394-(S)-(3-甲氧基苯硫基)-表没食子儿茶素没食子酸酯(JP-39)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为3-甲氧基苯硫酚，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-39，白色粉末，收率26.7％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z597.1059[M+H]+,calcd,597.1061)；1HNMR(500MHz,DMSO-d6)δ:7.31(1H,m,5″′-H),7.18(1H,d,J＝2.5,2″′-H),7.13(1H,dd,J＝9.0,2.5,6″′-H),6.86(1H,dd,J＝9.0,2.5,4″′-H),6.75(2H,s,2″,6″-H),6.35(2H,s,2′,6′-H),5.99(1H,d,J＝2.5,8-H),5.88(1H,d,J＝2.5,6-H),5.46(1H,s,3-H),5.22(1H,d,J＝2.5,2-H),4.58(1H,d,J＝2.5,4-H),3.81(3H,s,-OCH3)；13C NMR(125MHz,DMSO-d6)δ:164.9(O-C-O),159.7(C-3″′),158.4(C-5),157.3(C-7),155.6(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.9(C-4″),136.2(C-1″′),132.5(C-4′),130.0(C-1′),127.6(C-5″′),121.4(C-6″′),118.4(C-1″),114.2(C-2″′),112.8(C-4″′),108.7(C-2″,6″),105.2(C-2′,6′),96.0(C-10),95.9(C-6),94.2(C-8),72.8(C-2),70.8(C-3),55.1(C-OCH3),41.2(C-4).
实施例404-(S)-(3,4-二甲氧基苯硫基)-表没食子儿茶素没食子酸酯(JP-40)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为3,4-二甲氧基苯硫酚，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-40，白色粉末，收率27.1％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z627.1172[M+H]+,calcd,627.1167)；1HNMR(500MHz,DMSO-d6)δ:7.16(1H,dd,J＝9.0,2.5,6″′-H),7.14(1H,d,J＝2.5,2″′-H),7.00(1H,d,J＝9.0,2.5,5″′-H),6.71(1H,s,2″,6″-H),6.36(2H,s,2′,6′-H),5.99(1H,d,J＝2.5,8-H),5.86(1H,d,J＝2.5,6-H),5.45(1H,brs,3-H),5.20(1H,brs,2-H),4.41(2H,d,J＝2.5,4-H),3.81(3H,s,4″′-OCH3),3.78(3H,s,3″′-OCH3)；13C NMR(125MHz,DMSO-d6)δ:164.8(O-C-O),158.3(C-5),157.3(C-7),155.6(C-9),148.9(C-4″′),148.7(C-3″′),145.8(C-3′,5′),145.4(C-3″,5″),138.8(C-4″),132.5(C-4′),127.8(C-1′),124.8(C-1″′),124.7(C-6″′),118.5(C-1″),115.4(C-5″′),112.2(C-2″′),108.7(C-2″,6″),105.2(C-2′,6′),96.6(C-10),96.0(C-6),94.2(C-8),72.6(C-2),70.8(C-3),55.5(C-4″′-OCH3),55.4(C-3″′-OCH3),42.7(C-4).
实施例414-(S)-(3-氨基苯硫基)-表没食子儿茶素没食子酸酯(JP-41)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为3-氨基苯硫酚，高效制备液相45％(MeOH/H2O体积比)得到化合物JP-41,白色粉末，收率20.1％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z604.0874[M+H]+,calcd,604.0884)；1HNMR(500MHz,DMSO-d6)δ:7.05(1H,m,2″′-H),6.78(2H,m,5″′,6″′-H),6.73(2H,s,2″,6″-H),6.51(1H,dd,J＝8.0,2.0,4″′-H),6.35(1H,s,2′,6′-H),5.98(1H,d,J＝2.0,8-H),5.87(1H,d,J＝2.0,6-H),5.51(1H,brs,3-H),5.23(1H,brs,2-H),5.18(2H,brs,-NH2),4.47(1H,d,J＝2.0,4-H)；13C NMR(125MHz,DMSO-d6)δ:164.6(O-C-O),158.3(C-5),157.3(C-7),155.6(C-9),149.3(C-3″′),145.8(C-3′,5′),145.4(C-3″,5″),138.9(C-4″),134.9(C-1″′),132.5(C-4′),129.6(C-1′),127.8(C-5″′),118.5(C-1″),117.5(C-6″′),115.3(C-2″′),112.9(C-4″′),108.7(C-2″,6″),105.2(C-2′,6′),96.5(C-10),95.9(C-6),94.1(C-8),72.7(C-2),70.6(C-3),41.5(C-4).
实施例424-(S)-(2-甲氧基苯硫基)-表没食子儿茶素没食子酸酯(JP-42)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2-甲氧基苯硫酚，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-42，白色粉末，收率30.1％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z597.1068[M+H]+,calcd,597.1061)；1HNMR(500MHz,DMSO-d6)δ:7.70(1H,dd,J＝8.0,1.5,6″′-H),7.30(1H,m,4″′-H),7.08(1H,dd,J＝8.0,1.5,3″′-H),7.02(1H,m,5″′-H),6.74(2H,s,2″,6″-H),6.33(1H,s,2′,6′-H),5.98(1H,d,J＝2.5,8-H),5.88(1H,d,J＝2.5,6-H),5.54(1H,brs,2-H),5.18(1H,d,J＝2.0,3-H),4.54(1H,d,J＝2.5,4-H),3.85(3H,s,-OCH3)；13C NMR(125MHz,DMSO-d6)δ:164.8(O-C-O),158.3(C-5),157.4(C-7),155.7(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.8(C-4″),132.5(C-4′),130.8(C-1′),128.2(C-6″′),127.8(C-4″′),122.6(C-1″),121.1(C-5″′),118.6(C-1″′),111.4(C-3″′),108.7(C-2″,6″),105.2(C-2′,6′),96.3(C-10),96.0(C-6),94.2(C-8),72.9(C-2),70.3(C-3),55.8(C-OCH3),40.4(C-4).
实施例434-(S)-(1-烯丙基硫基)-表没食子儿茶素没食子酸酯(JP-43)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为1-烯丙基硫醇，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-43，白色粉末，收率13.6％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z531.0949[M+H]+,calcd,531.0956)；1HNMR(500MHz,DMSO-d6)δ:6.76(2H,s,2″,6″-H),6.40(2H,s,2′,6′-H),6.01(1H,m,2″′-H),5.92(1H,d,J＝2.0,8-H),5.82(1H,d,J＝2.0,6-H),5.36(1H,s,3-H),5.31(1H,d,J＝18.0,3″′-H),5.25(1H,s,2-H),5.11(1H,d,J＝10.5,3″′-H),3.97(1H,s,4-H),3.46(2H,m,1″′-H)；13C NMR(125MHz,DMSO-d6)δ:165.0(O-C-O),157.9(C-5),157.2(C-7),155.4(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.8(C-4″),134.7(C-2″′),132.5(C-4′),127.8(C-1′),118.6(C-1″),117.2(C-3″′),108.7(C-2″,6″),105.3(C-2′,6′),97.3(C-10),95.9(C-6),94.0(C-8),72.7(C-2),71.1(C-3),38.7(C-4),34.6(S-C).
实施例444-(S)-(1-丁硫基)-表没食子儿茶素没食子酸酯(JP-44)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为1-丁硫醇，高效制备液相65％(MeOH/H2O体积比)得到化合物JP-44，白色粉末，收率11.3％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z547.1269[M+H]+,calcd,547.1269)；1HNMR(500MHz,DMSO-d6)δ:6.77(2H,s,2″,6″-H),6.40(2H,s,2′,6′-H),5.92(1H,d,J＝2.0,8-H),5.82(1H,d,J＝2.0,6-H),5.34(1H,s,3-H),5.18(1H,s,2-H),3.95(1H,s,4-H),2.81(2H,m,1″′-H),1.69(2H,m,2″′-H),1.46(2H,m,3″′-H),0.92(3H,t,4″′-H)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),157.8(C-5),157.2(C-7),155.2(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.8(C-4″),132.5(C-4′),127.9(C-1′),118.6(C-1″),108.7(C-2″,6″),105.2(C-2′,6′),97.7(C-10),95.9(C-6),94.0(C-8),72.6(C-2),71.7(C-3),40.0(C-4),31.4(C-1″′,2″′),21.2(C-3″′),13.5(C-4″′).
实施例454-(S)-(环戊硫基)-表没食子儿茶素没食子酸酯(JP-45)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为环戊硫醇，高效制备液相65％(MeOH/H2O体积比)得到化合物JP-45，白色粉末，收率17.6％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z559.1267[M+H]+,calcd,559.1269)；1HNMR(500MHz,DMSO-d6)δ:6.77(2H,s,2″,6″-H),6.40(2H,s,2′,6′-H),5.91(1H,d,J＝2.0,8-H),5.82(1H,d,J＝2.0,6-H),5.33(1H,s,3-H),5.24(1H,s,2-H),3.99(1H,d,J＝2.0,4-H),3.51(1H,m,1″′-H),2.09(2H,m,2″′,5″′-H),1.74(2H,m,2″′,5″′-H),1.55(4H,m,3″′,4″′-H)；13C NMR(125MHz,DMSO-d6)δ:165.2(O-C-O),157.7(C-5),157.0(C-7),155.0(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.8(C-4″),132.5(C-4′),127.9(C-1′),118.6(C-1″),108.7(C-2″,6″),105.2(C-2′,6′),97.9(C-10),95.9(C-6),94.0(C-8),72.7(C-2),71.9(C-3),44.3(S-C),40.0(C-4),33.8(C-2″′),33.5(C-5″′),24.6(C-3″′),24.2(C-4″′).
实施例464-(S)-(3-甲基-2-(R)-丁硫基)-表没食子儿茶素没食子酸酯(JP-46)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为3-甲基2-丁硫醇，高效制备液相45％(CH3CN/H2O体积比)得到化合物JP-46，棕色油状物，收率11.3％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z561.1442[M+H]+,calcd,561.1425)；1HNMR(500MHz,DMSO-d6)δ:6.74(2H,s,2″,6″-H),6.37(2H,s,2′,6′-H),5.89(1H,d,J＝2.0,8-H),5.80(1H,d,J＝2.0,6-H),5.35(1H,s,3-H),5.12(1H,s,2-H),3.91(1H,d,J＝2.0,4-H),3.07(1H,m,2″′-H),1.87(1H,m,3″′-H),1.38(3H,d,J＝3.0,1″′-H),1.01(3H,d,J＝6.5,3″′-CH3),0.93(3H,d,J＝6.5,3″′-CH3)；13C NMR(125MHz,DMSO-d6)δ:165.4(O-C-O),157.9(C-5),157.2(C-7),155.3(C-9),145.9(C-3′,5′),145.5(C-3″,5″),139.0(C-4″),132.6(C-4′),128.1(C-1′),118.5(C-1″),108.8(C-2″,6″),105.3(C-2′,6′),97.9(C-10),96.0(C-6),94.1(C-8),72.8(C-2),72.0(C-3),47.9(C-2″′),40.4(C-4),32.8(C-3″′),19.7(C-1″′),19.3(C-3″′-CH3),19.1(C-3″′-CH3).
实施例474-(S)-(3-甲基-2-(S)-丁硫基)-表没食子儿茶素没食子酸酯(JP-47)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为3-甲基2-丁硫醇，高效制备液相45％(CH3CN/H2O体积比)得到化合物JP-47，棕色油状物，收率9.1％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z561.143[M+H]+,calcd,561.1425)；1H NMR(500MHz,DMSO-d6)δ:6.75(2H,s,2″,6″-H),6.39(2H,s,2′,6′-H),5.90(1H,d,J＝2.0,8-H),5.80(1H,d,J＝2.0,6-H),5.37(1H,s,3-H),5.15(1H,s,2-H),3.97(1H,d,J＝2.0,4-H),3.15(1H,m,2″′-H),2.00(1H,m,3″′-H),1.30(3H,d,J＝3.0,1″′-H),1.00(3H,d,J＝6.5,3″′-CH3),0.96(3H,d,J＝6.5,3″′-CH3)；13C NMR(125MHz,DMSO-d6)δ:165.4(O-C-O),157.9(C-5),157.3(C-7),155.3(C-9),145.9(C-3′,5′),145.5(C-3″,5″),139.0(C-4″),132.6(C-4′),128.1(C-1′),118.7(C-1″),108.8(C-2″,6″),105.3(C-2′,6′),98.0(C-10),96.0(C-6),94.1(C-8),72.6(C-2),72.4(C-3),47.7(C-2″′),40.4(C-4),32.8(C-3″′),19.3(C-1″′),19.0(C-3″′-CH3),18.6(C-3″′-CH3).
实施例484-(S)-(2-丁氧基-2-氧代乙硫基)-表没食子儿茶素没食子酸酯(JP-48)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2-巯基乙酸，反应溶剂为正丁醇，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-48，白色粉末，收率28.5％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z605.1339[M+H]+,calcd,605.1337)；1HNMR(500MHz,DMSO-d6)δ:6.78(2H,s,2″,6″-H),6.43(2H,s,2′,6′-H),5.95(1H,d,J＝2.0,8-H),5.85(1H,d,J＝2.0,6-H),5.35(1H,s,3-H),5.30(1H,s,2-H),4.15(1H,d,J＝1.5,4-H),4.10(2H,m,1″′-H),3.63(2H,m,S-C-H),1.57(2H,m,2″′-H),1.33(2H,m,3″′-H),0.85(3H,t,4″′-H)；13C NMR(125MHz,DMSO-d6)δ:170.7(O-C-OCH2),165.5(O-C-O),158.8(C-5),157.9(C-7),156.0(C-9),146.3(C-3′,5′),145.9(C-3″,5″),139.3(C-4″),133.1(C-4′),128.2(C-1′),119.1(C-1″),109.1(C-2″,6″),106.0(C-2′,6′),97.2(C-10),96.4(C-6),94.6(C-8),73.2(C-2),71.3(C-3),65.1(C-1″′),40.0(C-4),34.2(S-C),30.5(C-2″′),19.1(C-3″′),14.0(C-4″′).
实施例494-(S)-(2-甲氧基-2-氧代乙硫基)-表没食子儿茶素没食子酸酯(JP-49)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2-巯基乙酸，高效制备液相45％(MeOH/H2O体积比)得到化合物JP-49，白色粉末，收率27.9％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z563.0864[M+H]+,calcd,563.0867)；1HNMR(500MHz,DMSO-d6)δ:6.78(2H,s,2″,6″-H),6.43(2H,s,2′,6′-H),5.95(1H,d,J＝2.0,8-H),5.85(1H,d,J＝2.0,6-H),5.34(1H,s,3-H),5.29(1H,s,2-H),4.11(1H,d,J＝2.0,4-H),3.69(3H,m,-O-C-O-CH3),3.63(2H,m,S-CH2)；13C NMR(125MHz,DMSO-d6)δ:171.1(O-C-OCH3),165.5(O-C-O),158.8(C-5),157.8(C-7),155.9(C-9),146.3(C-3′,5′),145.9(C-3″,5″),139.3(C-4″),133.1(C-4′),128.2(C-1′),119.1(C-1″),109.2(C-2″,6″),105.7(C-2′,6′),97.3(C-10),96.4(C-6),94.6(C-8),73.2(C-2),71.5(C-3),52.7(C-OCH3),40.0(C-4),34.2(S-C).
实施例504-(S)-(1-甲氧基-1-氧代-2-丙硫基)-表没食子儿茶素没食子酸酯(JP-50)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2-巯基丙酸，高效制备液相50％(MeOH/H2O体积比)得到化合物JP-50，白色粉末，收率27.3％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z577.1024[M+H]+,calcd,577.101)；1H NMR(500MHz,DMSO-d6)δ:6.77(2H,d,J＝2.5,2″,6″-H),6.38(2H,d,J＝2.5,2′,6′-H),5.92(1H,d,J＝2.0,8-H),5.82(1H,d,J＝2.0,6-H),5.29(1H,s,3-H),5.23(1H,s,2-H),4.15(1H,s,4-H),3.85(1H,m,S-C-H),3.69(3H,s,-OCH3),1.48(3H,d,J＝7.0,-CH3)；13C NMR(125MHz,DMSO-d6)δ:172.9(O-C-OCH3),164.9(O-C-O),158.2(C-5),157.2(C-7),155.5(C-9),145.8(C-3′,5′),145.4(C-3″,5″),138.9(C-4″),132.6(C-4′),127.9(C-1′),118.6(C-1″),108.7(C-2″,6″),105.3(C-2′,6′),96.5(C-10),95.9(C-6),94.0(C-8),72.8(C-2),71.5(C-3),52.0(C-OCH3),40.8(S-C),40.0(C-4),17.5(C-CH3).
实施例514-(S)-(2-乙氧基-2-氧代乙硫基)-表没食子儿茶素没食子酸酯(JP-51)的制备
制备方法同制备例2，所用黄烷聚合物原料为狭叶红景天50％部位，所用硫代试剂为2-巯基乙酸，所用反应溶剂为无水乙醇，高效制备液相45％(MeOH/H2O体积比)得到化合物JP-51，白色粉末，收率27.9％。
化合物的核磁数据如下：
(c0.1MeOH)；HR-ESI-MS(m/z577.1018[M+H]+,calcd,577.101)；1HNMR(500MHz,DMSO-d6)δ:6.74(1H,s,2″,6″-H),6.39(2H,s,2′,6′-H),5.92(1H,d,J＝2.5,8-H),5.81(1H,d,J＝2.5,6-H),5.32(1H,s,3-H),5.25(1H,s,2-H),4.11(2H,m,S-C-H),4.09(1H,brs,4-H),3.60(3H,m,-O-CH2),1.17(3H,t,H-CH3)；13C NMR(125MHz,DMSO-d6)δ:170.1(O-C-OCH2),165.0(O-C-O),158.3(C-5),157.4(C-7),155.5(C-9),145.8(C-3′,5′),145.5(C-3″,5″),138.9(C-4″),132.6(C-4′),127.8(C-1′),118.7(C-1″),108.7(C-2″,6″),105.5(C-2′,6′),96.8(C-10),96.0(C-6),94.1(C-8),72.7(C-2),70.9(C-3),61.0(C-OCH2),40.3(C-4),33.9(S-C),14.0(C-CH3).
2.黄烷衍生物单体化合物的药理活性实验
实验例1黄烷衍生物对α-葡萄糖苷酶的抑制作用
实验方法：
以化学试剂p-Nitrophenyl-alpha-D-glucopyranoside(pNPG)为底物，在α-葡萄糖苷酶的作用下生成葡萄糖和p-Nitrophenol(pNP)，后者在波长400nm处有吸收峰。将受试药与α-葡萄糖苷酶预孵后，检测受试药对生成产物pNP量的影响；并计算受试药的IC50。
实验结果：
黄烷衍生物对α-葡萄糖苷酶具有明显抑制作用，其终浓度为66.7μM时对α-葡萄糖苷酶活性的抑制率及其IC50如表3所示。
表3化合物α-葡萄糖苷酶的抑制作用
实验例2黄烷衍生物对小鼠口服蔗糖耐量的影响
实验方法：
正常雄性ICR小鼠，体重22-26g。禁食过夜，随机组：对照组、阳性对照药糖组和给药组，分别口服水、阳性对照药阿卡波糖10mg/kg、和黄烷衍生物50mg/kg。在给药的同时口服双糖蔗糖4g/kg。测定蔗糖负荷后0、30、60、120min时的血糖水平，并计算血糖-时间曲线下面积(AUC)，即进行蔗糖耐量(OSTT)实验。
实验结果：
结果显示(见图1-4和表4-7)，与阿卡波糖的作用类似，黄烷衍生物JP-3、JP-7、JP-12、JP-16、JP-22、JP-47可明显减少正常小鼠蔗糖负荷后的血糖升高，使血糖-时间曲线下面积AUC值明显降低。
表4.蔗糖负荷后的血糖水平(mg/dl)(图1)
表5.蔗糖负荷后的血糖-时间曲线下面积(AUC)(图2)
表6.蔗糖负荷后的血糖水平(mg/dl)(图3)
表7.蔗糖负荷后的血糖-时间曲线下面积(AUC)(对应图4)
Claims (16)
1.一类具有通式I所示结构的黄烷化合物：
其中，通式I中R1选自-H、-OH；
其中，通式I中R选自取代的苄基，取代或非取代的芳杂环乙基，取代或非取代的芳杂环甲基，取代的苯，取代或非取代的脂肪基，取代或非取代的羧酸酯；
上述的“取代的苄基”指的是取代基个数为1～5的苄基，其取代基选自C1～5的烷基、C1～5的烯基、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代或非取代的芳杂环乙基”指的是杂原子个数为1～3的五元或六元芳杂环乙基，其芳杂环的杂原子选自N、O、S，取代基选自C1～5的烷基、C1～5的烯基、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代或非取代的芳杂环甲基”指的是杂原子个数为1～3的五元或六元芳杂环甲基，其芳杂环的杂原子选自N、O、S，取代基选自C1～5的烷基、C1～5的烯基、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代的苯”指的是取代基个数为1～5的苯基，其取代基选自C1～5的烷基、C1～5的烯基、C1～5的烷氧基、-NH2、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代或非取代的脂肪基”中脂肪基选自C1～5的直链或支链烷基、C1～5的直链或支链烯基、C5～6的环烷基，其取代基选自C1～5的烷氧基、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
上述的“取代或非取代的羧酸酯”指的是形成羧酸酯的羧酸链部分和醇链部分均为C1～5的直链或支链烷基、C1～5的直链或支链烯基，其中形成羧酸酯的羧酸链部分和醇链部分可以相同，也可以不同，其取代基选自C1～5的烷氧基、-NHRa、-NRaRa、氟、氯、溴、-CN、-NO2；
其中，上述的“Ra”指的是C1～5的直链或支链烷基、C1～5的直链或支链烯基。
2.根据权利要求1的化合物，其特征在于：所述的化合物选自通式Ia：
其中，R1选自H、OH；
其中，R2、R3、R4、R5、R6独立的选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基，并且R2、R3、R4、R5、R6不同时为氢。
3.根据权利要求1的化合物，其特征在于：所述的R选自取代或非取代的吡嗪乙基、取代或非取代的嘧啶乙基、取代或非取代的哌嗪乙基、取代或非取代的吡啶乙基、取代或非取代的呋喃乙基、取代或非取代的吡咯乙基、取代或非取代的噻吩乙基、取代或非取代的噻唑乙基；
其中，取代基均选自甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基。
4.根据权利要求3的化合物，其特征在于：所述的化合物选自通式Ib：
其中，R1选自H、OH；
其中，R7、R8、R9独立的选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基。
5.根据权利要求1的化合物，其特征在于：所述的R选自取代或非取代的吡嗪甲基、取代或非取代的嘧啶甲基、取代或非取代的哌嗪甲基、取代或非取代的吡啶甲基、取代或非取代的呋喃甲基、取代或非取代的吡咯甲基、取代或非取代的噻吩甲基、取代或非取代的噻唑甲基；
其中，取代基均选自甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基。
6.根据权利要求5的化合物，其特征在于：所述的化合物选自通式Ic：
其中，R1选自H、OH；
其中，R10、R11、R12独立的选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基。
7.根据权利要求1的化合物，其特征在于：所述的化合物选自通式Id：
其中，R1选自H、OH；
其中，R13、R14、R15、R16、R17独立的选自氢、甲基、氟、氯、甲氧基、乙氧基、丙氧基、异丙氧基、氨基、甲氨基、二甲氨基、乙胺基、二乙胺基、异丙氨基、二异丙氨基、硝基，并且R13、R14、R15、R16、R17不同时为氢。
8.根据权利要求1的化合物，其特征于：所述的R选自甲基、乙基、丁基、异丙基、烯丙基、异丙烯基、丁烯基、环戊基、环己基、3-甲基丁基-2-基。
9.根据权利要求1的化合物，其特征在于：所述的R选自如下羧酸酯类取代基：
羧酸酯类取代基
。
10.根据权利要求1-9任一所述的化合物，其特征在于：所述的化合物选自：
R1＝H的化合物结构与名称
R1＝OH的化合物结构与名称
。
11.根据权利要求1-10任一项所述的化合物的制备方法，其特征在于：所述的化合物的制备通法如下：
1)采集大花红景天及狭叶红景天各20kg，80％乙醇提取3次后浓缩，得到浸膏，然后向浸膏中加入质量比10倍量的蒸馏水于10℃左右静置96h，上清液浓缩后经依次经水、5％乙醇、50％乙醇、95％乙醇四个梯度进行大孔树脂分离，取50％水-乙醇部位，浓缩冷冻干燥，得到两种富含不同类型黄烷聚合物的部位；
2)取一定量的黄烷聚合物溶于质量比1:30的无水甲醇中，然后加入质量比1:0.5的硫代试剂R-SH，质量比1:0.5的48％的HBr水溶液，加热搅拌于60℃条件下反应4h后，HPLC监测反应完毕，向反应液中加入与反应液质量比5:1的蒸馏水，乙酸乙酯萃取3次，合并有机层，有机层经无水硫酸钠干燥后，浓缩至干燥得到粗品，粗品经200～300目的硅胶柱粗分后，以质量分数MeOH:H2O＝30％～70％的甲醇水溶液为流动相，高压制备液相得到相应的目标产物；反应通式如路线1所示：
其中，R、R1的定义与权利要求1-10任一项中的R、R1相同。
12.一种药物组合物，其特征在于：含有有效剂量权利要求1-10任一所述的化合物和药学上可接受的赋形剂。
13.根据权利要求12的药物组合物，其特征在于：所述组合物的剂型选自片剂、胶囊剂、丸剂、颗粒剂、口服液和混悬剂。
14.权利要求1-10任一所述的化合物在制备预防和/或治疗肥胖症的产品中的应用。
15.权利要求1-10任一所述的化合物在制备预防和/或治疗糖尿病或糖耐量异常的产品中的应用。
16.根据权利要求14-15任一项的应用，其特征在于：所述的产品选自药品、保健品。
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