CN107417595A - 一种基于自由基串联反应的系列单萜吲哚生物碱骨架及天然产物的合成方法 - Google Patents

一种基于自由基串联反应的系列单萜吲哚生物碱骨架及天然产物的合成方法 Download PDF

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CN107417595A
CN107417595A CN201710187443.XA CN201710187443A CN107417595A CN 107417595 A CN107417595 A CN 107417595A CN 201710187443 A CN201710187443 A CN 201710187443A CN 107417595 A CN107417595 A CN 107417595A
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秦勇
刘小宇
宋颢
张丹
汪小蓓
夏栋梁
秦文芳
周瑞捷
周骁汉
周启龙
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Sichuan University
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Abstract

本发明涉及医药化工领域，公开了一种基于自由基串联反应的系列单萜吲哚生物碱骨架及天然产物合成方法。本发明提供的三种类型光催化自由基串联反应突破了苯胺与烯胺的传统反应模式，高选择性地构筑多个C–N及C–C键，快速形成分子结构的复杂性和官能团的多样性；以该方法为关键步骤，发展了高效、通用的策略来合成系列单萜吲哚生物碱骨架和相应天然产物。本发明所述合成方法和所涉及的天然产物合成步骤简短，操作方便，原料及试剂都价廉易得，可以广泛推广应用。

Description

一种基于自由基串联反应的系列单萜吲哚生物碱骨架及天然 产物的合成方法
技术领域
本发明涉及医药化工领域，具体的说是涉及一种光催化自由基串联反应技术合成系列单萜吲哚生物碱骨架及相应天然产物的方法。
背景技术
单萜吲哚生物碱类天然产物由于其复杂多样的分子结构和显著的生物活性成为药学、化学和生物学研究领域关注的焦点。目前已知的单萜吲哚生物碱天然产物数量和骨架类型众多，多数表现出重要的药理学活性，其中在临床上使用的代表性的药物分子包括降血压药利血平(reserpine)，抗心律失常药阿马林(ajmaline)及抗癌药长春碱(vinblastine)和长春新碱(vincristine)等。
生源合成上(O’Connor,S.E.；Maresh,J.J.Nat.Prod.Rep.2006,23,532)，单萜吲哚生物碱是以色胺(tryptamine)与裂环番木鳖苷(secologanin)为前体物，两者在异胡豆苷合酶(STR1)作用下经Mannich反应缩合得到异胡豆苷(strictosidine)，随后经异胡豆葡萄糖苷酶(SGD)脱去葡萄糖得到柯南因型(corynanthe)的基本骨架，进一步的生物合成次级修饰可转化得到其他的骨架类型。根据单萜部分碳骨架单元是否发生重排，单萜吲哚生物碱可分为三大类，即柯南因型(corynanthe)、白坚木型(aspidosperma)和依波加明型(iboga)；三者可分别再进一步衍生出更多具有不同亚型的骨架。反应方程式示意如下：
如何有效地获取具有重要生理活性的单萜吲哚生物碱是天然药物研发过程中备受关注的课题。由于自然资源有限，通过化学合成来制备这些天然分子及其类似物是解决这一难题的主要手段。尽管到目前为止国内外众多研究团队对单萜吲哚生物碱的合成进行了详细研究(生物碱化学，王峰鹏主编，化学工业出版社:北京,2008年；P293-340)，然而已知方法通常只能合成某类骨架中的一个或少数几个分子，且存在路线繁琐、产率低、成本高以及通用性不强等问题。
发明内容
为克服现有技术中存在的缺陷，本发明以光催化的自由基串联反应为关键技术，提供了一种如式II、II’、III-VI所示的六种类型单萜吲哚生物碱骨架的制备方法，该方法具有高效、简洁、通用性强的优点，同时，通过所制备骨架还可以完成相应生理活性天然产物的合成。上述式II、II’、III-VI都是通过式I经光催化的自由基串联反应来制备的。
因此，本发明的目的在于提供式I所示的自由基反应底物和如式II、II’、III-VI所示的不同类型的单萜吲哚生物碱骨架。
本发明的第二的目的在于提供如式I-VI所示的化合物的制备方法。
本发明的第三个目的在于提供如式III所示的化合物在天然产物合成中的应用。
一种如式I所示的自由基反应底物，具有如下结构：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；
R选自(1)：其中n为0-3之间的整数；R3，R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构；
或者R选自(2)：其中n为0-3之间的整数；R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构；
或者R为(3)：苄基或对甲氧基苄基；
或者R为(4)：其中R7选自吸电子基团或亚甲基连接的离去基团。
本发明还提供了一种式I所示化合物的制备方法，包括如下步骤：
步骤一，烯醛化合物VII与手性胺催化剂VIII及丙二酸酯反应，得到式IX所示化合物。
此步骤中反应溶剂为乙醇，反应温度为25℃。R1的含义与式I所述含义相同。
步骤二，式IX所示化合物经溶剂处理后，在碱性条件下制备式X所示化合物。
此步骤中反应温度为25℃，先用二氯甲烷与三氟乙酸混合液处理，优选混合溶剂体积比5:4，处理后抽干溶剂，以甲苯为溶剂进行反应，碱试剂为三乙胺。R1的含义与式I所述含义相同。步骤三，式X所示化合物在酸性条件下和胺缩合，生成式XI所示化合物。
此步骤中，反应温度为80℃，反应溶剂为甲苯，酸为醋酸和分子筛。R1和R的含义与式I所述含义相同。
步骤四，式XI所示化合物的硝基在还原剂作用下还原为胺，得到式XII所示化合物。
此步骤中，反应溶剂为甲醇，还原剂为锌粉和甲酸铵，反应温度为25℃。R1和R的含义与式I所述含义相同。
步骤五，碱性条件下，式XII所示化合物的胺基被保护，得到式I所示化合物，即自由基反应底物。
此步骤中，反应溶剂为二氯甲烷，碱为吡啶。R1、R2和R的含义与式I所述含义相同。
在制备得到式I所示化合物的基础上，本发明提供了一种在可见光光照条件下，经三种不同类型自由基关键反应制备六种类型单萜吲哚生物碱骨架的方法。该方法的关键技术点在于式I中苯胺的N-H键均裂产生氮自由基，所生成自由基可进一步发生不同类型的串联反应，从而完成如式II、II’、III-VI所示的六种类型单萜吲哚生物碱骨架的制备。
自由基串联反应类型一：如式I所示的自由反应底物在可见光光照条件下，通过N–H键的均裂产生氮自由基，并进一步经分子内/分子内自由基串联反应过程，一步构建如式II或 II’所示的吲哚生物碱骨架的四环体系。式II和II’具有如下结构：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；n为0-3之间的整数；R3，R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构。
本发明提供了式II所示化合物的制备方法，包括如下步骤，式I所示化合物在光照条件下，在光敏剂和碱的存在下，发生自由基串联反应，得到式II所示化合物：
此步骤中，光源为可见光，优选为5W蓝色LED灯；光敏剂可使用Ir(dtbbpy)(ppy)2PF6， Ru(bby)3Cl2·6H2O，Ir(dF(CF3)ppy)2(bpy)PF6和Ru(bby)3Cl2等，优选为Ir(dtbbpy)(ppy)2PF6；碱可使用各种无机碱及有机碱如碳酸钾、碳酸铯、碳酸氢钾、三乙胺、二异丙基乙基胺等，优选为碳酸氢钾；温度可为0℃到50℃，优选为35℃；溶剂可使用各类有机溶剂如甲苯、1,2- 二氯乙烷、二氧六环、N,N-二甲基甲酰胺、四氢呋喃、乙腈、二氯甲烷及相应溶剂与水的混合溶剂，优选为四氢呋喃。
R1、R2、R3、R4、R5的含义与式II所述含义相同。R选自其中n为0-3之间的整数。
本发明提供了式II’所示化合物的制备方法，包括如下步骤，式I所示化合物在光照条件下，在光敏剂和碱的存在下，发生自由基串联反应，得到式II’所示化合物：
此步骤中，光源、光敏剂、碱、温度、溶剂的含义与式II制备中各含义相同。R1、R2、R4、R5的含义与式II所述含义相同。R选自其中n为0-3之间的整数。
自由基串联反应类型二：如式I所示的自由反应底物在可见光光照条件下，经分子内/ 分子间/分子内自由基串联反应过程，一步构建如式III所示的吲哚生物碱骨架的四环体系。式III具有如下结构：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；R6和R7选自各种吸电子基团或亚甲基连接的离去基团。
本发明提供了式III所示化合物的制备方法，包括如下步骤，式I所示化合物在光照条件下，在光敏剂和碱的存在下，与化合物发生自由基串联反应，得到式III所示化合物：
此步骤中，光源、光敏剂、碱、温度、溶剂的含义与式II制备过程中各含义相同。R1、R2、 R6的含义与式III所述含义相同。R为其中R7选自吸电子基团或亚甲基连接的离去基团。
自由基串联反应类型三：如式I所示的自由反应底物在可见光光照条件下，与不同的自由基受体经分子内/分子间自由基串联反应过程，一步构建如式IV、V或VI所示的吲哚生物碱三环骨架体系。式IV、V和VI具有如下结构：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；R为苄基或对甲氧基苄基；R8为吸电子基团。
本发明提供了式IV所示化合物的制备方法，包括如下步骤，式I所示化合物在光照条件下，在光敏剂和碱的存在下，分别与化合物发生自由基串联反应，分别得到式IV、式V或式VI所示化合物：
此步骤中，光源、光敏剂、碱、温度、溶剂的含义与式II制备过程中各含义相同。R、R1、 R2的含义与式I所述含义相同，R8的含义与式IV所述含义相同。
在通过上述自由基串联反应方法快速合成不同类型的单萜吲哚生物碱骨架的基础上，利用该关键技术，本发明还以式III在天然产物(+)-Yohimbane全合成中的应用为例，还提供了一种通过所构建骨架高效合成相应单萜吲哚生物碱天然产物分子的方法。天然产物 (+)-Yohimbane及其类似物具有降血压和镇静的活性(Scott,J.A.；Crews,F.T.J.Pharmacol.Exp.Ther.1983,224,640)，其合成路线包括如下步骤：
步骤一，化合物III-j在室温下溶于乙酸乙酯，加入氢氧化钯进行催化氢化制备化合物1。步骤二，室温下，化合物1的甲醇溶液用硼氢化钠处理合成得到一对不可分离的非对映异构体2a/b。
步骤三，化合物2a/b溶于四氢呋喃中，依次加入氢化钠，二硫化碳及碘甲烷，在0℃到室温下反应，产物进一步与正丁基氢化锡和AIBN在甲苯中加热到80℃反应合成化合物3。
步骤四，化合物3在室温下与镁和甲醇反应脱去氮原子的对甲苯磺酰基保护，制备化合物4。步骤五，40℃下，化合物26的四氢呋喃溶液用苯亚硒酸酐处理，生成化合物5。
步骤六，室温下，化合物5溶于四氢呋喃中，加入Rh(H)(CO)(PPh3)3和苯硅烷进行反应生成天然产物(+)-Yohimbane。
反应方程式示意如下：
本发明提供的三种类型光催化自由基串联反应突破了苯胺与烯胺的传统反应模式，高选择性地构筑多个C–N及C–C键，快速形成分子结构的复杂性和官能团的多样性；以该方法为关键步骤，发展了高效、通用的策略来合成系列单萜吲哚生物碱骨架和相应天然产物。本发明所述合成方法和所涉及的天然产物合成步骤简短，操作方便，原料及试剂都价廉易得，可以广泛推广应用。
具体实施方式
本发明实施例公开了一种基于自由基串联反应的系列单萜吲哚生物碱骨架及天然产物合成方法。本领域技术人员可以借鉴本文内容，适当改进工艺参数实现。特别需要指出的是，所有类似的替换和改动对本领域技术人员来说是显而易见的，它们都被视为包括在本发明。本发明的方法已经通过较佳实施例进行了描述，相关人员明显能在不脱离本发明内容、精神和范围内对本文所述的方法进行改动或适当变更与组合，来实现和应用本发明技术。
为了进一步理解本发明，下面结合实施例对本发明进行详细说明。
实施例1：化合物IX的制备
将化合物VII(10.0g,0.056mol,1.0equiv.)、叔丁基甲基马来酸酯(12.3ml,0.074mol,1.3equiv.)和(2S)-2-[二苯基[(三甲基硅酯)氧基]甲基]-吡咯烷VIII(3.7g,0.011mol,0.2equiv.)置于250mL圆底烧瓶中,并加入100mL乙醇搅拌。室温反应16h后,抽干溶剂。柱层析(石油醚:乙酸乙酯,5:1,v/v)得到两个非对映异构体IX-a和IX-b(共15.1g), 收率76％。
化合物IX-a和IX-b的检测数据如下：IX-a:TLC(石油醚:乙酸乙酯,5:1v/v):Rf＝0.30；1H NMR(400MHz,CDCl3):δ9.68(s,1H),7.81(d,J＝8.8Hz,1H),7.55(t,J＝7.2 Hz,1H),7.46(d,J＝7.6Hz,1H),7.39(t,J＝8.4Hz,1H),4.56–4.50(m,1H), 3.83(d,J＝9.2Hz,1H),3.57(s,3H),3.12–2.97(m,2H),1.43(s,9H)；13C NMR (100MHz,CDCl3):δ199.6,167.9,166.5,150.3,134.8,132.8,129.3,128.2,124.7, 83.2,57.2,52.6,46.6,33.7,27.8,27.8,27.8；IR(neat):vmax＝1727,1355,845,749 cm-1；HRMS(m/z):[M+Na]+calcd.forC17H21NNaO7,374.1210；found 374.1210；[α]D 25＝ +63.4(c 0.20,MeOR)。IX-b:TLC(石油醚:乙酸乙酯,5:1v/v):Rf＝0.26；1H NMR(400 MHz,CDCl3):δ9.68(s,1H),7.82(d,J＝8.4Hz,1H),7.55(t,J＝8Hz,1H),7.46 (d,J＝7.6Hz,1H),7.38(t,J＝7.6Hz,1H),4.53–4.47(m,1H),3.87(d,J＝ 9.6Hz,1H),3.73(s,3H),3.08–2.94(m,2H),1.20(s,9H)；13C NMR(100MHz,CDCl3): δ199.6,168.4,165.9,150.2,135.0,132.9,129.5,128.2,124.7,82.8,57.1,52.7, 47.3,34.1,27.4,27.4,27.4；IR(neat):vmax＝1727,1529,844,787cm–1；HRMS(m/z):[M+Na]+calcd.for C17H21NNaO7374.1210；found 374.1210；[α]D 25＝+32.5(c 0.30,MeOH)。实施例2：化合物X的制备
混合物IX-a和IX-b(40.2g,0.114mol,1.0equiv.)用二氯甲烷(333mL)溶解后,慢慢加入三氟醋酸(267mL)。室温反应3h后,抽干溶剂。剩余物用二氯甲烷(200mL)溶解后, 再抽干溶剂。此操作重复三次,除去残留的三氟醋酸。粗品用甲苯(333mL)溶解后,加入三乙胺(23.7mL,0.170mol,1.5equiv.)。反应回流2h,抽干溶剂后,加入水(100mL)和饱和食盐水(200mL)。用乙酸乙酯萃取三次(3×500mL),合并有机相,无水硫酸钠干燥,抽干溶剂,柱层析(石油醚:乙酸乙酯,3:1,v/v)纯化得化合物X(17.1g),收率60％。HPLC(AD-H,异丙醇:正己烷＝5:95,流速1.0mL/min,λ＝254nm,tmajor＝24.23min,tminor＝25.93min) 测定手性化合物X的ee值为96％。
化合物X的检测数据如下：TLC(石油醚:乙酸乙酯,3:1v/v):Rf＝0.30；1H NMR(400MHz, CDCl3):δ9.70(s,1H),7.79(d,J＝8.0Hz,1H),7.57(t,J＝7.6Hz,1H),7.41–7.35(m,2H),4.32–4.24(m,1H),3.58(s,3H),2.92(d,J＝7.2Hz,2H),2.77(dd, J＝7.6,3.2Hz,2H)；13C NMR(100MHz,CDCl3):δ199.5,171.2,150.0,136.8,132.9, 128.2,127.8,124.5,51.8,48.8,39.5,30.4；IR(neat):vmax＝1732,1526,856,787 cm–1；HRMS(m/z):[M+Na]+calcd.for C12H13NNaO5,274.0686；found,274.0686；[α]D 25＝+13.7(c 0.70,MeOH)。
实施例3：化合物I-a～I-j的制备
以I-a的制备为例进行说明：
将化合物X(890mg,3.55mmol,1.0equiv.)、3-丁烯-1-胺(324μL,3.91mmol,1.1equiv.)、冰乙酸(406μL,7.10mmol,2.0equiv.)和分子筛(粉末,890mg)的混合物用甲苯(178mL)溶解后,加热至80℃。保持该温度搅拌8h后,滤除分子筛,并用二氯甲烷洗涤,抽干溶剂。粗品经柱层析(石油醚:乙酸乙酯,5:1,v/v)纯化得到XI-a(704mg),收率73％。化合物XI-a(700mg,2.57mmol,1.0equiv.)用甲醇(35mL)溶解后,加入活化的锌粉(1.8g,0.028mol,11.0equiv.)和甲酸铵(1.6g,0.026mol,10.0equiv.)。滤除固体,抽干滤液。剩余物用二氯甲烷溶解,并用饱和氯化铵水溶液(40mL)洗涤。水层用二氯甲烷萃取三次(3×10mL),合并有机相,无水硫酸钠干燥,抽干溶剂得苯胺化合物粗品。将粗品用干燥二氯甲烷(35mL)溶解,加入吡啶(3.7mL,0.051mol,20.0equiv.)和对甲苯磺酰氯(980mg,5.14mmol,2.0equiv.)。室温搅拌30分钟后,加入饱和氯化铵水溶液(35mL)淬灭反应。二氯甲烷萃取三次(3×10mL),合并有机相,无水硫酸钠干燥,抽干溶剂,柱层析(石油醚:乙酸乙酯,5:1, v/v)纯化得化合物I-a(622mg),两步收率61％。
化合物XI-a的检测数据如下：TLC(石油醚:乙酸乙酯,5:1v/v):Rf＝0.28；1H NMR(600 MHz,CDCl3):δ7.86(d,J＝7.8Hz,1H),7.55(t,J＝7.8Hz,1H),7.47(d,J＝7.8 Hz,1H),7.42–7.36(m,1H),6.23(dd,J＝7.8,1.2Hz,1H),5.81–5.74(m,1H), 5.16(dd,J＝7.8,4.2Hz,1H),5.12–5.03(m,2H),4.31(q,J＝7.2Hz,1H),3.66 (dt,J＝13.2,7.2Hz,1H),3.52(dt,J＝13.2,7.2Hz,1H),3.02(dd,J＝16.8,7.8 Hz,1H),2.69(dd,J＝16.8,7.2Hz,1H),2.36(q,J＝7.2Hz,2H)；13C NMR(150MHz, CDCl3):δ167.4,148.9,137.2,134.7,133.3,131.2,129.1,127.9,124.7,117.4,107.6, 45.8,38.5,33.5,33.1；IR(neat):vmax＝2924,1662,1522,1885,1350cm–1；HRMS(m/z): [M+Na]+calcd.for C15H16N2Na O3,295.1053；found,295.1055；[α]D 20＝-207.0(c 0.40, CHCl3)。化合物I-a的检测数据如下：TLC(石油醚:乙酸乙酯,5:1v/v):Rf＝0.30；1H NMR (600MHz,CDCl3):δ7.58(d,J＝8.4Hz,2H),7.25–7.15(m,4H),7.12(td,J＝ 7.8,1.2Hz,1H),7.06–7.01(m,1H),6.68(s,1H),6.12(dd,J＝7.8,1.8Hz,1H), 5.82–5.75(m,1H),5.17–5.03(m,2H),4.95(dd,J＝7.8,3.6Hz,1H),4.01–3.96(m,1H),3.61–3.52(m,2H),2.57(dd,J＝16.2,7.2Hz,1H),2.41(s,3H), 2.40–2.32(m,3H)；13C NMR(100MHz,CDCl3):δ168.0,143.7,139.3,136.4,134.7, 133.1,130.1,129.5,129.5,127.9,127.6,127.5,127.2,127.2,127.1,117.2,109.4, 45.7,38.5,33.0,32.6,21.5；IR(neat):vmax＝2926,1656,1264,1162cm–1；HRMS(m/z): [M+Na]+calcd.forC22H24N2NaO3S,419.1400；found 419.1400；[α]D 20＝-72.0(c 0.23, CHCl3)。
参考化合物I-a的合成，化合物X与不同的胺进行缩合，再还原硝基及进一步保护苯胺氮原子即可制备对应的化合物I-b～I-j。
化合物I-b的检测数据如下：收率：49％；TLC(石油醚:乙酸乙酯,1:1v/v):Rf＝0.55；1H NMR(600MHz,CDCl3):δ7.53(d,J＝7.8Hz,2H),7.35(t,J＝7.2Hz,2H),7.30 (t,J＝7.2Hz,1H),7.25(d,J＝4.2Hz,1H),7.16(d,J＝7.8Hz,2H),7.13–7.07 (m,3H),7.07–7.00(m,2H),6.11(d,J＝6.0Hz,1H),4.91(dd,J＝7.8,3.6Hz, 1H),4.75(d,J＝14.4Hz,1H),4.68(d,J＝14.4Hz,1H),4.06–3.94(m,1H),2.68 (dd,J＝16.2,7.2Hz,1H),2.44(dd,J＝16.2,9.6Hz,1H),2.35(s,3H)；13C NMR (150MHz,CDCl3):δ168.2,143.7,139.0,136.9,136.4,133.1,129.7,129.5,129.5, 128.7,128.7,127.9,127.8,127.8,127.7,127.6,127.6,127.4,127.2,127.2,110.1, 49.0,38.6,32.7,21.5；IR(neat):vmax＝3222,2920,1660,1383,1165,661,548cm–1； HRMS(m/z):[M+Na]+calcd.for C25H24N2NaO3S,455.1399；found,455.1384；[α]D 25＝- 44.7(c 0.67,CHCl3)。
化合物I-c的检测数据如下：收率：52％；TLC(石油醚:乙酸乙酯,3:1v/v):Rf＝0.65；1H NMR(400MHz,CDCl3):δ7.58(d,J＝8.0Hz,2H),7.26–7.13(m,4H),7.12–7.06 (m,1H),7.05–6.98(m,2H),6.09(dd,J＝7.6,1.6Hz,1H),5.44(s,1H),4.94 (dd,J＝7.6,3.6Hz,1H),4.07–3.98(m,1H),3.62–3.50(m,2H),2.58(dd,J ＝16.0,7.2Hz,1H),2.40(s,3H),2.35(dd,J＝16.4,9.6Hz,1H),2.18(t,J＝6.8 Hz,2H),2.02–1.92(m,4H),1.67–1.48(m,4H)；13C NMR(100MHz,CDCl3):δ167.7, 143.8,139.2,136.4,134.2,133.1,130.3,129.6,129.6,128.0,127.6,127.5,127.3, 127.3,126.8,123.7,108.7,44.8,38.4,36.8,32.8,28.2,25.3,22.9,22.2,21.5； IR(neat):vmax＝2929,1655,1387,1332,1264,1161cm–1；HRMS(m/z):[M+Na]+calcd for C26H30N2NaO3S,473.1869；found 473.1856；[α]D 25＝-53.7(c 0.82,CHCl3)。
化合物I-d的检测数据如下：收率：46％；TLC(石油醚:乙酸乙酯,3:1v/v):Rf＝0.40；1H NMR(600MHz,CDCl3)δ7.56(d,J＝7.8Hz,2H),7.20–7.13(m,4H),7.06(t,J ＝7.2Hz,1H),6.98(d,J＝7.8Hz,1H),6.12(d,J＝7.8Hz,1H),5.75(dt,J＝11.4, 6.0Hz,1H),5.40(dt,J＝11.4,7.2Hz,1H),4.95(dd,J＝7.8,4.2Hz,1H),4.29 (d,J＝6.0Hz,2H),4.21(qd,J＝15.0,7.2Hz,2H),4.09–4.06(m,1H),2.64(dd, J＝16.2,7.2Hz,1H),2.42–2.32(m,4H),0.90(s,9H),0.08(s,6H)；13C NMR(100 MHz,CDCl3):δ167.9,143.5,139.4,136.4,133.2,133.1,129.4,129.4,129.1,127.7, 127.6,127.4,127.3,127.2,127.2,125.2,110.0,59.1,42.3,38.5,32.5,25.8,25.8, 25.8,21.4,18.2,–5.3,–5.3；IR(neat):vmax＝3207,2953,2928,2855,1650,1599, 1491,1461,1407,1383,1335,1252,1161,1091cm–1；HRMS(m/z):[M+Na]+calcd.for C28H38NaN2O4SSi,549.2214；found,549.2208；[α]D 20＝-24.0(c 2.8,CHCl3)。
化合物I-e的检测数据如下：收率：41％；TLC(石油醚:乙酸乙酯,10:1v/v):Rf＝0.20；1H NMR(400MHz,CDCl3):δ7.58(d,J＝8.4Hz,2H),7.26–7.21(m,3H),7.17(t, J＝7.6Hz,1H),7.12–7.08(m,1H),7.02(d,J＝8.0Hz,1H),6.65(s,1H),6.26 (dd,J＝8.0,1.0Hz,1H),4.89(dd,J＝7.6,4.0Hz,1H),4.01–3.99(m,1H),3.77 –3.74(m,2H),3.65(dt,J＝13.6,4.8Hz,1H),3.57(dt,J＝13.6,5.6Hz,1H), 2.59(dd,J＝16.4,7.6Hz,1H),2.40–2.34(m,4H),0.89(s,9H),0.06(s,6H)；13C NMR(150MHz,CDCl3):δ168.0,143.7,139.2,136.4,133.1,131.9,129.5,129.5, 127.9,127.6,127.4,127.2,127.2,126.8,107.7,61.6,48.8,38.4,32.5,25.8,25.8, 25.8,21.5,18.1,-5.4,-5.4；IR(neat):vmax＝2927,2856,1650,1161,1091,564cm–1；HRMS(m/z):[M+Na]+calcd.for C26H36N2NaO4SSi,523.2057；found,523.2054；[α]D 25＝–41.4(c 0.28,CHCl3)。
化合物I-f的检测数据如下：收率：46％；TLC(石油醚:乙酸乙酯,1:1v/v):Rf＝0.80；1H NMR(400MHz,CDCl3):δ7.58(d,J＝8.4Hz,2H),7.26–7.15(m,4H),7.11(td, J＝8.0,2.0Hz,1H),7.03(d,J＝7.6Hz,1H),6.78–6.71(m,1H),6.18(dd,J ＝8.0,1.6Hz,1H),4.93(dd,J＝7.6,3.6Hz,1H),4.30–3.95(m,1H),3.65(dt, J＝6.0Hz,2H),3.58(t,J＝6.8Hz,2H)2.57(dd,J＝16.0,7.2Hz,1H),2.41(s, 3H),2.36(dd,J＝16.0,6.4Hz,1H),1.85–12.7(m,2H),0.90(s,9H),0.06(s, 6H)；13C NMR(100MHz,CDCl3):δ167.8,144.0,138.9,136.3,133.1,131.0,129.6, 129.6,128.0,127.7,127.6,127.3,127.3,126.7,108.5,60.0,43.6,38.4,33.0,31.5, 25.9,25.9,25.9,21.6，18.2，5.4,5.4；IR(neat):vmax＝2927,1651,1410,1335, 1385,1162,1091cm-1；HRMS(m/z):[M+Na]+calcd.forC27H38N2NaO4SSi,537.2214；found, 537.2194；[α]D 25＝-35.8(c 0.26,CHCl3)。
化合物I-g的检测数据如下：收率：48％；TLC(石油醚:乙酸乙酯,1:1v/v):Rf＝0.80；1H NMR(400MHz,CDCl3):δ7.57(d,J＝8.0Hz,2H),7.25–7.14(m,4H),7.10(td, J＝6.8,1.6Hz,1H),7.03(d,J＝8.0Hz,1H),6.94(s,1H),6.13(dd,J＝7.6,1.6 Hz,1H),4.94(dd,J＝7.6,3.6Hz,1H),4.04–3.93(m,1H),3.63(t,J＝6.4Hz, 2H),3.52(td,J＝6.8,2.0Hz,2H),2.58(dd,J＝16.0,7.2Hz,1H),2.40(s,3H), 2.36(dd,J＝16.0,6.4Hz,1H),1.70–1.58(m,2H),1.58–1.46(m,2H),0.89 (s,9H),0.05(s,6H)；13C NMR(100MHz,CDCl3)δ167.8,143.9,139.1,136.4,133.1, 130.2,129.6,129.6,127.9,127.7,127.5,127.3,127.3,127.0,109.1,62.7,46.0, 38.4,32.8,29.8,25.9,25.9,25.9,25.1，21.5，18.3，5.3，,5.3；IR(neat):vmax＝2928,2856,1649,1410,1387,1334,1255,1160,1091cm–1；HRMS(m/z):[M+Na]+ calcd.for C28H40N2NaO4SSi,551.2370；found,551.2354；[α]D 25＝-38.0(c1.00,CHCl3)。化合物I-h的检测数据如下：收率：45％；TLC(石油醚:乙酸乙酯,1:1v/v):Rf＝0.80；1H NMR(600MHz,CDCl3):δ7.58(d,J＝7.8Hz,2H),7.23(d,J＝8.4Hz,2H),7.21 –7.14(m,2H),7.13–7.08(m,1H),7.02(d,J＝7.8Hz,1H),6.96–6.89(m, 1H),6.12(dd,J＝7.8,1.8Hz,1H),4.95(dd,J＝7.8,4.2Hz,1H),4.04–3.96 (m,1H),3.60(t,J＝6.6Hz,2H),3.55–3.41(m,2H),2.58(dd,J＝16.2,7.8Hz, 1H),2.40(s,3H),2.36(dd,J＝16.2,9.6Hz,1H),1.64–1.49(m,4H),1.40–1.29 (m,2H),0.89(s,9H),0.04(s,6H)；13C NMR(150MHz,CDCl3):δ167.8,143.9,139.0, 136.4,133.1,130.3,129.6,129.6,127.9,127.6,127.6,127.3,127.3,126.9,108.9, 63.0,46.3,38.4,32.8,32.5,28.4,26.0,26.0,26.0,23.1，21.5，18.3，5.3,5.3； IR(neat):vmax＝2928,2855,1650,1410,1258,1160,1091cm–1；HRMS(m/z):[M+Na]+ calcd.for C29H42N2NaO4SSi,565.2527；found,565.2503；[α]D 25＝-62.6(c 0.46,CHCl3)。
化合物I-i的检测数据如下：收率：43％；TLC(石油醚:乙酸乙酯,5:1v/v):Rf＝0.40；1H NMR(400MHz,CDCl3):δ7.57(d,J＝8.4Hz,2H),7.24(d,J＝8.0Hz,2H),7.21 –7.17(m,2H),7.12(dt,J＝8.8,4.0Hz,1H),7.04(d,J＝8.0Hz,1H),6.72(s, 1H),6.17(dd,J＝7.6,1.6Hz,1H),4.94(dd,J＝7.6,3.6Hz,1H),4.32(s,2H), 4.03–3.94(m,1H),3.70–3.50(m,2H),2.56(dd,J＝16.4,7.2Hz,1H),2,41 (s,3H),2.37(dd,J＝16.0,10.0Hz,1H),2.26(t,J＝7.2Hz,2H),1.85–1.70 (m,2H),0.91(s,9H),0.12(s,6H)；13C NMR(100MHz,CDCl3):δ167.9,144.0,138.9, 136.3,133.1,130.6,129.7,129.7,127.9,127.7,127.6,127.3,127.3,127.0,109.0, 83.8,79.6,51.9,45.5,38.4,32.9,27.4,25.9,25.9,25.9,21.6，18.3，16.2，5.1, 5.1；IR(neat):vmax＝3213,2927,2856,1653,1409,1334,1255,1161,1075cm–1； HRMS(m/z):[M+Na]+calcd.for C30H40N2NaO4SSi,575.2370；found,575.2347；[α]D 25＝ -52.8(c 0.25,CHCl3)。
化合物I-j的检测数据如下：收率：48％；TLC(石油醚:乙酸乙酯,2:1v/v):Rf＝0.20；1H NMR(400MHz,CDCl3):δ7.58(d,J＝8.0Hz,2H),7.25–7.22(m,3H),7.19(td, J＝7.2,0.8,1H),7.12(td,J＝8.0,1.6Hz,1H),7.00(d,J＝7.6Hz,1H),6.51(s, 1H),6.37(dd,J＝8.0,2.0Hz,1H),5.05(dd,J＝7.6,3.6Hz,1H),4.35(dd,J＝ 17.2,2.4Hz,1H),4.23(dd,J＝17.2,2.4Hz,1H),4.09–4.01(m,1H),2.59(dd, J＝16.8,7.6Hz,1H),2.42(s,3H),2.40–2.34(m,1H),1.85(t,J＝2.4Hz,3H)；13C NMR(100MHz,CDCl3):δ167.5,143.9,139.1,136.3,133.1,129.6,129.6,128.9, 128.1,127.8,127.6,127.3,127.3,127.0,109.8,80.5,73.2,38.4,35.0,32.8,21.5, 3.6；IR(neat):vmax＝2962,1653,1263,1161,1091cm–1；HRMS(m/z):[M+Na]+calcd. for C22H22N2NaO3S,417.1243；found,417.1241；[α]D 20＝-45.4(c 0.28,CHCl3)。
实施实例4：化合物I-s的合成
将化合物I-e(7.5g,0.014mol,1.0equiv.)溶解到300mL四氢呋喃中，加入四丁基氟化铵(11.2g,0.036mol,2.5equiv.)，室温反应6小时候反应完全，加水淬灭反应，反应液用水萃取三次(3×100mL)，合并的水层用含5％三乙胺的乙酸乙酯萃取三次(3×80 mL)，合并的有机相用无水硫酸钠干燥，过滤，抽干溶剂,柱层析(石油醚:乙酸乙酯,1:5,v/v) 纯化得化合物I-s(5.3g),收率90％。
化合物I-s的检测数据如下：TLC(石油醚:乙酸乙酯,1:2v/v):Rf＝0.20；1H NMR(400 MHz,CDCl3):δ7.57(d,J＝8.0Hz,2H),7.23(d,J＝8.0Hz,2H),7.19(dd,J＝ 4.4Hz,2H),7.14–7.01(m,1H),6.97(d,J＝7.6Hz,1H),6.16(dd,J＝7.6,1.6 Hz,1H),5.89(m,1H),5.56–5.45(m,1H),5.02(dd,J＝7.6,3.6Hz,1H),4.25 (d,J＝6.8Hz,2H),4.20(t,J＝6Hz,2H),4.14–4.04(m,1H),2.60(dd,J＝16.4, 7.2Hz,1H),2.45–2.34(m,5H)；13C NMR(100MHz,CDCl3):δ168.3,143.7,139.5, 136.4,133.1,132.6,129.5,129.5,127.8,127.5,127.4,127.2,125.8,110.5,57.9, 43.1,38.4,32.5,21.5；IR(neat):vmax＝2923,1643,1491,1410,1382,1330,1260, 1158,1090cm–1；HRMS(m/z):[M+Na]+calcd for C22H24NaN2O4S,435.1349；found,435.1354； [α]D 25＝+70.4(c 2.6,CHCl3)。
实施实例5：化合物I-k的合成
将化合物I-s(10.0g,0.024mol,1.0equiv.)溶于400mL二氯甲烷中，分三次加入戴斯-马丁试剂(15.0g,0.036mol,1.5equiv.)。室温搅拌15分钟后加入硫代硫酸钠和碳酸氢钠水溶液淬灭反应，水层用二氯甲烷萃取三次(3×30mL)，合并有机相，用无水硫酸钠干燥，抽干溶剂，得到的粗产物用300mL溶解，加入对甲苯磺酸(57.3mg,2.43mmol,0.1 equiv.)，室温搅拌20分钟以后，加碳酸氢钠饱和水溶液淬灭反应，水层用二氯甲烷萃取三次(3×25mL)，合并的有机相用无水硫酸钠干燥，过滤，抽干溶剂,柱层析(石油醚:乙酸乙酯,2:1,v/v)纯化得化合物I-k(8.2g),收率82％。
化合物I-k的检测数据如下：TLC(石油醚:乙酸乙酯,1:2v/v):Rf＝0.40；1H NMR(600 MHz,CDCl3):δ9.59(d,J＝7.8Hz,1H),7.56(d,J＝8.4Hz,2H),7.22(m,5H), 7.13(s,1H),7.05(d,J＝7.8Hz,1H),6.82(dt,J＝15.6,4.8Hz,1H),6.11(dd, J＝16.2,8.4Hz,1H),6.03(d,J＝7.8Hz,1H),4.98(s,1H),4.51(d,J＝18Hz, 1H),4.35(d,J＝18Hz,1H),4.09(t,J＝9.6Hz,1H),2.68(dd,J＝16.8,7.2Hz, 1H),2.45(m,1H),2.38(s,3H)；13C NMR(150MHz,CDCl3):δ192.9,168.2,151.2, 143.9,139.0,136.4,133.2,132.5,129.6,129.2,127.8,127.8,127.7,127.5,127.2, 111.1,46.7,38.5,32.9,21.5；IR(neat):vmax＝3222,1657,1491,1404,1381,1330, 1290,1158,1091cm–1；HRMS(m/z):[M+Na]+calcd.forC22H22NaN2O4S,433.1192；found, 433.1188；[α]D 25＝-43.3(c 1.00,CHCl3)。
实施例6：化合物II和II’的制备
以化合物II-a的合成为例进行说明：化合物II-b～II-g，II’均参照II-a的合成方法制备。
溶解,35℃下用5W蓝色LED灯照射18h。抽干溶剂,柱层析(石油醚:乙酸乙酯,2:1,v/v)纯化得II-a(35.1mg),收率70％。II-a的dr值(>50:1)通过LC-MS确定: MeCN/H2O,30％(0min)→40％(6min)→30％(14min)→30％(15min),流速(0.4mL/min), 保留时间tR＝7.63min。(此反应将溶剂换成四氢呋喃:水＝1:1,v/v,得34.1mg产物II-a, 收率68％。
化合物II-a的检测数据如下：TLC(石油醚:乙酸乙酯,2:1v/v):Rf＝0.30；1H NMR(600MHz, CDCl3):δ7.69(d,J＝7.8Hz,1H),7.41(d,J＝8.4Hz,2H),7.29(t,J＝7.8Hz,1H),7.16(t,J＝7.2Hz,1H),7.14(d,J＝8.4Hz,2H),6.97(d,J＝7.2Hz,1H), 4.27(t,J＝8.4Hz,1H),3.55(td,J＝7.8,3.0Hz,2H),3.48(td,J＝11.4,7.2 Hz,1H),3.02(q,J＝8.4Hz,1H),2.81–2.74(m,1H),2.70(dd,J＝17.4,9.6Hz, 1H),2.47(dd,J＝17.4,5.4Hz,1H),2.36(s,3H),1.89–1.82(m,1H),1.70(dd, J＝12.0,6.6Hz,1H),1.25(d,J＝7.0Hz,3H)；13C NMR(150 MHz,CDCl3):δ168.2, 144.5,140.8,137.3,134.4,129.7,129.7,128.4,127.2,127.2,126.7,123.8,120.0, 62.3,61.2,43.9,38.1,35.0,33.54,30.6,21.6,13.2；IR(neat):vmax＝2926,1642, 1461,1357,1264,1169 cm–1；HRMS(m/z):[M+Na]+calcd.forC22H24N2NaO3S,419.1400；found, 419.1396；[α]D 20＝+99.0(c 0.30,CHCl3)。
(d,J＝8.0Hz,2H),7.37–7.29(m,5H),7.28–7.10(m,4H),7.00(d,J＝7.2Hz, 1H),4.47(t,J＝9.2Hz,1H),3.81–3.64(m,2H),3.62–3.47(m,2H),3.09(q, J＝8.4Hz,1H),2.95–2.85(m,1H),2.76(dd,J＝17.2,9.2Hz,1H),2.52(dd, J＝17.2,5.6Hz,1H),2.36(s,3H),2.29(t,J＝12.8Hz,1H),1.77–1.70(m,1H), 1.62–1.52(m,1H)；13C NMR(100 MHz,CDCl3):δ168.1,144.5,140.7,140.2,137.1, 134.4,129.8,129.8,129.3,129.3,128.5,128.5,128.5,127.2,127.2,126.7,126.2, 123.8,120.0,61.7,61.2,43.8,42.3,38.1,33.6,31.8,25.8,21.6；IR(neat):vmax＝2925,1643,1459,1353,1260,1166,1090,1019cm-1；HRMS(m/z):[M+Na]+calcd.for C28H28N2NaO3S,495.1713；found,495.1720；[α]D 25＝+45.1(c 0.28,CHCl3)。
–7.27(m,3H),7.18(t,J＝7.6Hz,1H),7.13(d,J＝8.0Hz,2H),6.94(t,J＝ 8.0Hz,1H),4.25–4.15(m,1H),3.77(s,3H),3.69–3.60(m,2H),3.55(dd,J ＝16.4,6.4Hz,1H),3.40(dt,J＝11.2,6.8Hz,1H),3.08–2.99(m,1H),2.88(q, J＝8.0Hz,1H),2.72(dd,J＝16.4,9.2Hz,1H),2.50(dd,J＝16.4,9.6Hz,1H), 2.43–2.36(m,1H),2.35(s,3H),2.00–1.77(m,2H)；13C NMR(100MHz,CDCl3): δ172.9,168.2,144.6,140.7,137.8,133.8,129.6,129.6,128.5,127.3,127.3,127.3, 123.9,120.6,63.2,58.5,51.7,44.0,37.8,37.6,33.9,32.1,28.1,21.5；IR(neat): vmax＝2952,1733,1654,1459,1354,1166cm-1；HRMS(m/z):[M+Na]+calcd.for C24H26N2NaO5S,477.1455；found,477.1437。
–7.29(m,3H),7.19(t,J＝7.6Hz,1H),7.14(d,J＝8.0Hz,2H),6.96(d,J＝ 7.6Hz,1H),4.21–4.11(m,1H),3.68–3.56(m,3H),3.52(dd,J＝16.8,4.8Hz, 1H),3.02–2.91(m,2H),2.77(dd,J＝17.2,9.6Hz,1H),2.61(dd,J＝16.8,10.8 Hz,1H),2.44(dd,J＝17.2,6.0Hz,1H),2.36(s,3H),2.19–1.96(m,2H)；13C NMR (100MHz,CDCl3):δ168.1,145.0,140.3,137.3,133.6,129.8,129.8,128.7,127.4, 127.2,127.2,124.0,120.6,118.7,62.6,59.1,43.8,37.9,37.6,33.6,27.9,21.6, 16.3；IR(neat):vmax＝2962,1652,1263,1090,1014cm-1；HRMS(m/z):[M+Na]+calcd. for C23H23N3NaO3S,444.1352；found,444.1366；[α]D 25＝+74.1(c 0.48,CHCl3)。
J＝7.6Hz,2H),7.65–7.46(m,3H),7.41–7.34(m,1H),7.30–7.15(m,4H), 7.08(d,J＝8.0Hz,2H),6.92(d,J＝7.6Hz,1H),4.35(dd,J＝16.4,5.6Hz,1H), 4.26(dd,J＝10.4,8.0Hz,1H),3.85–3.77(m,1H),3.74(dd,J＝10.4,6.4Hz, 1H),3.42–3.31(m,1H),3.28–3.12(m,2H),2.83(dt,J＝16.0,8.0Hz,1H), 2.73(dd,J＝15.6,9.2Hz,1H),2.38(dd,J＝16.0,7.2Hz,1H),2.34(s,3H),2.08 –1.96(m,1H),1.90–1.80(m,1H)；13C NMR(150MHz,CDCl3):δ199.0,168.3,144.7, 140.7,138.1,136.8,133.6,133.2,129.6,129.6,128.6,128.6,128.5,128.5,128.5, 127.5,127.4,127.4,124.0,120.8,64.0,57.7,44.3,37.6,37.5,37.1,34.3,28.3, 21.6；IR(neat):vmax＝3054,2925,1651,1448,1354,1265,1166cm-1；HRMS(m/z):[M –H]+calcd.for C29H27N2O4S,499.1770；found,499.1672。
J＝8.0Hz,1H),7.31(t,J＝7.6Hz,1H),7.23–7.17(m,3H), 7.09(d,J＝8.0Hz,2H),6.90(d,J＝7.6Hz,1H),4.98(d,J＝12.0Hz,1H),4.16 (dd,J＝10.4,7.6Hz,1H),4.00–3.92(m,1H),3.91(s,3H),3.90–2.83(m,1H), 3.81(s,3H),3.25–3.05(m,2H),2.79–2.61(m,2H),2.34(s,3H),2.31–2.22 (m,1H).1.94–1.85(m,2H)；13C NMR(100MHz,CDCl3):δ169.9,168.6,168.1,144.9, 140.6,138.2,133.0,129.6,129.6,128.6,127.8,127.6,127.6,124.1,121.1,64.2, 56.2,52.8,52.5,50.9,44.3,41.7,37.5,34.6,26.5,21.6；IR(neat):vmax＝2953, 1750,1656,1433,1353,1162cm-1；HRMS(m/z):[M+Na]+calcd.for C26H28N2NaO7S,535.1509； found,535.1496。
1H),7.34(d,J＝8.0Hz,2H),7.28(t,J＝8.0Hz,1H),7.16(t,J＝7.2Hz,1H), 7.11(d,J＝8.0Hz,2H),6.94(d,J＝7.6Hz,1H),4.27–4.06(m,5H),3.62– 3.44(m,3H),2.94(q,J＝8.4Hz,2H),2.90–2.77(m,1H),2.70(dd,J＝16.8, 9.6Hz,1H),2.41(dd,J＝17.2,6.4Hz,1H),2.33(s,3H),2.35–12.25(m,1H), 1.98–1.79(m,2H),1.36(t,J＝6.8Hz,6H)；13C NMR(100MHz,CDCl3):δ168.1, 144.6,140.6,137.4,133.9,129.6,129.6,128.5,127.2,127.2,127.1,123.9,120.3, 62.7,61.9,61.6,60.3,44.0,37.7,36.1,33.6,27.8,23.2,21.8,21.5,16.4；IR(neat): vmax＝2980,1648,1353,1165,1020,959,730,665cm-1；HRMS(m/z):[M+Na]+calcd. for C26H33N2NaO6PS,555.1689；found,555.1663.
MeCN/H2O,30％(0min)→40％(6min)→40％(14min)→30％(15min),流速(0.4mL/min), 保留时间tR1＝9.91min,tR2＝10.66min。TLC(石油醚:丙酮,2:1,v/v):Rf＝0.30；1H NMR(400MHz,CDCl3):δ7.77–7.69(m,5H),7.33–7.18(m,5H),7.13–6.95(m, 2H),4.94(d,J＝9.2Hz,1H),4.33(d,J＝12.8Hz,1H),3.80(s,1H),3.65(s,1H), 3.60(s,1H),3.22–3.13(m,1H),2.50–2.32(m,3H),2.42(s,3H),2.39(s,3H), 1.95(d,J＝13.2Hz,1H),1.75–1.57(m,1H),1.54–1.33(m,2H)；13C NMR(150 MHz,CDCl3):δ167.4,144.3,144.2,141.3,141.1,135.0,134.7,134.4,129.8,129.8, 129.7,129.7,128.6,128.0,127.3,127.3,125.5,123.2,117.6,66.1,61.4,59.0,43.3, 37.6,31.4,26.8,21.6,21.6,19.2；IR(neat):vmax＝1637,1264,1164,1091cm-1；HRMS (m/z):[M+Na]+calcd.for C29H32N4NaO5S2,603.1706；found,603.1708。
酯,1:2v/v):Rf＝0.40；1H NMR(600MHz,CDCl3):δ10.00(s,1H),7.59(d,J＝7.0 Hz,1H),7.38(d,J＝8.4Hz,2H),7.22(t,J＝7.8Hz,1H),7.15(d,J＝7.8Hz, 2H),7.05(t,J＝7.2Hz,1H),7.01(d,J＝7.2Hz,1H),4.35(d,J＝12.6Hz,1H), 4.28(d,J＝9.6Hz,1H),3.55(d,J＝11.4Hz,1H),3.41–3.33(m,1H),3.26(dd, J＝19.2,7.8Hz,1H),2.79(dd,J＝16.8,6.0Hz,1H),2.76–2.69(m,1H),2.57 (dd,J＝19.8,3.0Hz,1H),2.52–2.46(m,1H,2.34(s,3H),2.30–2.20(m,1H), 1.88–1.80(m,1H),1.61–1.52(m,2H),1.51–1.40(m,1H)；13C NMR(150MHz, CDCl3):δ202.0,169.3,144.5,141.6,134.2,134.1,129.8,129.8,128.4,126.8,126.8 125.7,123.7,117.1,69.6,61.1,47.9,45.6,37.4,34.0,33.2,33.2,24.5,21.5；IR(neat):vmax＝2927,1656,1264,1166cm-1；HRMS(m/z):[M+Na]+calcd.for C24H26N2NaO4S,461.1506；found,461.1495；[α]D 25＝+36.3(c 0.37,CHCl3)。II-h’:TLC(石油醚:乙酸乙酯,1:1v/v):Rf＝0.25；1H NMR(600MHz,CDCl3):δ9.88(s,1H),7.66(d,J＝ 7.8Hz,1H),7.52(d,J＝8.4Hz,2H),7.28(s,1H),7.18(d,J＝7.8Hz,2H),7.11 (t,J＝7.8Hz,1H),7.01(d,J＝7.8Hz,1H),4.58–4.49(m,1H),4.32(dd,J＝ 9.0,4.2Hz,1H),3.88–3.79(m,1H),3.11(t,J＝7.8Hz,1H),3.03–2.95(m, 1H),2.73(dd,J＝18.0,2.4Hz,1H),2.63–2.50(m,3H),2.43(td,J＝12.6,3.6 Hz,1 H),2.36(s,3H),1.87–1.77(m,2H),1.58–1.48(m,2H)；13C NMR(150MHz, CDCl3):δ201.0,166.4,144.5,140.8,134.9,134.4,129.9,129.9,128.7,126.8,126.8, 126.0,123.3,118.2,65.6,62.1,43.4,42.1,37.6,31.9,30.9,29.3,21.6,19.6；IR(neat):vmax＝2927,1646,1264,1167cm–1；HRMS(m/z):[M+Na]+calcd.for C24H26N2NaO4S,461.1506；found,461.1496；[α]D 25＝+55.7(c 0.12,CHCl3)。
8.4Hz,2H),7.21(t,J＝7.6Hz,1H),7.17(d,J＝8.0Hz,2H),7.08–6.97(m, 2H),4.59(d,J＝10.4Hz,1H),4.40–4.31(m,1H),3.62(d,J＝10.8Hz,1H),3.43 –3.33(m,1H),2.74–2.64(m,1H),2.63–2.51(m,2H),2.35(s,3H),2.06(d, J＝13.2Hz,1H),1.94(d,J＝10.0Hz,1H),1.78–1.70(m,1H),1.63(d,J＝12.8 Hz,1H),1.50–1.26(m,6H),1.19–1.07(m,1H),1.05–0.92(m,1H)；13C NMR (150MHz,CDCl3):δ169.1,144.2,141.8,134.4,134.0,129.7,129.7,128.4,126.9, 126.9,125.4,123.6,116.9,68.9,58.9,46.7,45.9,43.5,37.3,33.4,33.2,32.3,28.6, 26.2,25.8,21.5；IR(neat):vmax＝2926,1649,1460,1264,1168cm–1；HRMS(m/z):[M +Na]+calcd.for C26H30N2NaO3S,473.1870；found,473.1881；[α]D 25＝+55.8(c 0.40,CHCl3)。
(m,7H),7.11(t,J＝7.2Hz,3.5H),7.05(d,J＝4.4Hz,3.5H),7.00(d,J＝7.2 Hz,3.5H),4.53(dd,J＝9.6,4.4Hz,2.5H),4.40–4.20(m,6H),4.11(t,J＝4.0 Hz,2.5H),3.78–3.64(m,3.5H),3.44–3.33(m,2.5H),2.98–2.36(m,18H), 2.37(s,3H),2.36(s,7.5H),2.0–1.40(m,21H)；13C NMR(150MHz,CDCl3):δ168.4, 167.9,144.7,141.4,140.8,134.6,133.6,133.4,132.6,131.4,129.9,129.9,129.8, 129.8,128.8,128.7,127.2,127.2,127.0,127.0,126.2,125.3,124.3,124.0,119.0, 118.6,117.6,115.6,68.7,64.7,63.8,62.5,50.2,46.1,39.1,38.6,37.7,37.6,34.5, 34.5,32.2,29.7,28.4,28.0,23.4,21.5,21.1,20.2,19.8；IR(neat):vmax＝2925, 1650,1479,1351,1265,1166,1089cm-1；HRMS(m/z):[M+Na]+calcd.for C25H27N3NaO3S, 472.1665；found,461.1660。
实施例7：化合物III的制备
化合物III-a的合成
将Ir(dtbbpy)(ppy)2PF6(0.6mg,0.609μmol,0.005equiv.)、KHCO3(61.6mg,0.610mmol,5.0equiv.)、丙炔酸甲酯(51.2mg,0.610mmol,5.0equiv)和底物I-k(50.0mg,0.122mmol,1.0equiv.)置于25mL干燥试管中,抽换氩气保护。混合物用干燥脱气四氢呋喃(5mL)溶解,35℃下用5W蓝色LED灯照射20h。抽干溶剂,柱层析(异丙醇：环己烷,1:10到1:4, v/v)纯化得III-a(36.1mg),收率60％，III-a-1(7.2mg),收率12％。III-a的dr值(>50:1) 通过LC-MS确定:MeCN/H2O,35％(0min)→35％(6min)→35％(14min)→35％(15min),流速(0.4mL/min),保留时间tR1＝5.76min,tR2＝6.07min。
化合物III-a的检测数据如下：TLC(异丙醇：环己烷,1:4v/v):Rf＝0.60；1H NMR(400MHz, CDCl3):δ9.70(s,1H),7.74(d,J＝8.0Hz,1H),7.56(s,1H),7.35–7.31(m, 3H),7.19(t,J＝7.6Hz,1H),7.13(d,J＝8.0Hz,2H),7.00(d,J＝7.6Hz,1H), 4.29(dd,J＝13.2,1.6Hz,1H),4.04–4.03(m,2H),3.84(s,3H),3.55–3.46 (m,1H),3.23–3.13(m,1H),3.05(dd,J＝13.2,3.6Hz,1H),2.92(dd,J＝14.8, 8.0Hz,1H),2.48–2.45(m,2H),2.39(dd,J＝15.2,10.0Hz,1H),2.34(s,3H)；13C NMR(150MHz,CDCl3):δ199.7,170.7,165.5,144.7,140.6,135.6,134.4,133.4, 132.8,129.7,129.7,128.9,127.1,127.1,126.9,124.3,119.5,65.1,52.9,52.3,45.1, 41.4,37.6,35.4,28.2,21.5；IR(neat):vmax＝3337,2925,1714,1658,1354,1167, 755,671cm-1；HRMS(m/z):[M+Na]+calcd.for C26H26N2NaO6S,517.1403；found,517.1400； [α]D 25＝+19.0(c 0.10,CHCl3)。
化合物III-a-1的检测数据如下：TLC(异丙醇：环己烷,1:4v/v):Rf＝0.50；1H NMR(400 MHz,CDCl3):δ9.48(d,J＝8.0Hz,1H),7.65(d,J＝8.0Hz,1H),7.57(d,J＝8.0 Hz,2H),7.29–7.26(m,1H),7.19(d,J＝8.0Hz,2H),7.10–7.05(m,2H),6.52 (dt,J＝15.6,5.2Hz,1H),6.22(t,J＝10.8Hz,1H),6.11(d,J＝11.6Hz,1H), 5.98(dd,J＝15.6,8.0Hz,1H),5.77(d,J＝9.6Hz,1H),4.58(dd,J＝16.8,4.4 Hz,1H),4.38(d,J＝10.0Hz,1H),3.96(dd,J＝16.8,6.0Hz,1H),3.82(s,3H), 3.70–3.65(m,1H),2.85(dd,J＝16.4,7.2Hz,1H),2.71(d,J＝16.0Hz,1H), 2.36(s,3H)；13C NMR(150MHz,CDCl3):δ193.1,168.6,165.4,150.6,144.4,141.4, 139.7,133.8,133.6,132.8,129.7,129.7,129.1,127.3,127.3,125.4,124.4,124.2, 116.2,64.7,59.4,52.1,46.6,37.7,35.4,21.5；IR(neat):vmax＝2925,1722,1664, 1354,1167,664cm–1；HRMS(m/z):[M+Na]+calcd.for C26H26N2NaO6S,517.1403；found, 517.1399；[α]D 25＝+46.5(c 0.33,CHCl3)。
化合物III-b的合成
将Ir(dtbbpy)(ppy)2PF6(0.5mg,0.568μmol,0.005equiv.)、KHCO3(56.8mg,0.568mmol, 5.0equiv.)、丙炔酸甲酯(47.7mg,0.568mmol,5.0equiv.)和底物I-l(50.0mg,0.114 mmol,1.0equiv.)置于25mL干燥试管中,抽换氩气保护。混合物用干燥脱气四氢呋喃(5mL) 溶解,35℃下用5W蓝色LED灯照射24h。抽干溶剂,柱层析(异丙醇：环己烷,1:10到1:4, v/v)纯化得III-b(37.5mg),收率63％，III-b-1(4.2mg),收率7％。III-b的dr值(48:1)通过LC-MS确定:MeCN/H2O,35％(0min)→35％(6min)→35％(14min)→35％(15min),流速(0.4mL/min),保留时间tR1＝7.94min,tR2＝8.41min.。III-b-1的Z/E值(10:1)通过LC-MS确定:MeCN/H2O,35％(0min)→35％(6min)→35％(14min)→35％(15min),流速(0.4 mL/min),保留时间tR1＝4.83min,tR2＝5.51min。
化合物III-b的检测数据如下：TLC(异丙醇：环己烷,1:4v/v):Rf＝0.50；1H NMR(600MHz, CDCl3):δ9.72(s,1H),7.56(s,1H),7.39(d,J＝8.4Hz,2H),7.31(d,J＝1.8 Hz,1H),7.16(d,J＝7.8Hz,2H),6.88(d,J＝8.4Hz,1H),6.73(dd,J＝8.4,1.8 Hz,1H),4.29(dd,J＝13.2,1.2Hz,1H),4.03–4.01(m,2H),3.87(s,3H),3.85 (s,3H),3.55–3.46(m,1H),3.12–3.10(m,1H),3.04(dd,J＝13.2,3.6Hz,1H), 2.88(dd,J＝15.0,8.4Hz,1H),2.51–2.45(m,2H),2.37–2.33(m,4H)；13C NMR (150MHz,CDCl3):δ199.7,170.8,165.5,160.4,144.7,141.8,134.5,133.5,132.7, 129.8,129.8,127.3,127.1,127.1,124.6,113.5,104.7,65.8,55.7,52.9,52.4,45.1, 41.4,37.0,35.8,28.2,21.5；IR(neat):vmax＝2924,1716,1662,1163,748,668cm–1； HRMS(m/z):[M+Na]+calcd.for C27H28N2NaO7S,547.1509；found,547.1503；[α]D 25＝+37.8 (c 0.57,CHCl3)。
化合物III-b-1的检测数据如下：TLC(异丙醇：环己烷,1:4v/v):Rf＝0.40；1H NMR(600 MHz,CDCl3):δ9.49(d,J＝7.8Hz,1H),7.58(d,J＝8.4Hz,2H),7.23(d,J＝2.4 Hz,1H),7.19(d,J＝8.1Hz,2H),6.93(d,J＝7.8Hz,1H),6.62(dd,J＝8.4,2.4 Hz,1H),6.54(dt,J＝16.2,6.0Hz,1H),6.20–6.16(m,1H),6.08(d,J＝11.4 Hz,1H),5.93(dd,J＝15.6,7.8Hz,1H),5.74(d,J＝10.2Hz,1H),4.59(dd,J＝ 16.8,3.6Hz,1H),4.36(dd,J＝10.2,1.8Hz,1H),3.95(dd,J＝16.8,5.4Hz,1H), 3.85(s,3H),3.81(s,3H),3.64–3.59(m,1H),2.80(dd,J＝16.2,7.2Hz,1H), 2.67(dd,J＝16.2,2.4Hz,1H),2.36(s,3H)；13C NMR(150MHz,CDCl3):δ193.1, 168.7,165.4,160.7,150.6,144.5,142.6,139.6,133.9,133.5,129.7,129.7,127.3, 127.3,124.6,124.5,124.3,111.7,102.0,65.3,59.7,55.7,52.1,46.6,37.2,35.6, 21.5；IR(neat):vmax＝2923,1722,1661,1163,734,666,588cm–1；HRMS(m/z):[M+ Na]+calcd.for C27H28N2NaO7S,547.1509；found,547.1500。
化合物III-c的合成
将Ir(dtbbpy)(ppy)2PF6(0.6mg,0.609μmol,0.005equiv.)、KHCO3(61.6mg,0.610mmol, 5.0equiv.)、3-炔基-2-丁酮(25.6mg,0.305mmol,2.5equiv.)和底物I-k(50.0mg,0.122 mmol,1.0equiv.)置于25mL干燥试管中,抽换氩气保护。混合物用干燥脱气四氢呋喃(5mL) 溶解,35℃下用5W蓝色LED灯照射24h。抽干溶剂,柱层析(异丙醇：环己烷,1:10到1:4, v/v)纯化得II-c(30.3mg),收率52％,III-c-1(12.8mg),收率22％。III-c的dr值(>50:1) 通过LC-MS确定:MeCN/H2O,32.5％(0min)→32.5％(6min)→32.5％(14min)→32.5％(15min), 流速(0.4mL/min),保留时间tR1＝3.44min,tR2＝7.52min。
化合物III-c的检测数据如下：TLC(异丙醇：环己烷,1:4v/v):Rf＝0.60；1H NMR(400MHz, CDCl3):δ9.67(s,1H),7.75(d,J＝8.4Hz,1H),7.52(d,J＝2.4Hz,1H),7.36 –7.32(m,3H),7.21–7.18(m,1H),7.15(d,J＝8.0Hz,2H),7.02(d,J＝7.6 Hz,1H),4.28(dd,J＝13.2,2.0Hz,1H),4.11(d,J＝8.0Hz,1H),4.03(t,J＝9.2 Hz,1H),3.60–3.54(m,1H),3.24(q,J＝8.8Hz,1H),2.99(dd,J＝13.2,3.6Hz, 1H),2.94(dd,J＝15.2,8.0Hz,1H),2.52(s,3H),2.39–2.37(m,3H),2.35(s, 3H)；13C NMR(100MHz,CDCl3):δ199.9,197.1,170.7,144.9,140.7,140.5,135.8, 135.3,133.2,129.8,129.8,128.9,127.1,127.1,126.9,124.3,119.3,65.2,52.6, 45.2,41.6,37.7,35.5,26.5,25.4,21.5；IR(neat):vmax＝2923,1720,1668,1353, 1167,753cm–1；HRMS(m/z):[M+Na]+calcd.for C26H26N2NaO5S,501.1454；found,501.1452； [α]D 25＝+14.4(c 0.50,CHCl3)。
化合物III-c-1的检测数据如下：TLC(异丙醇：环己烷,1:4v/v):Rf＝0.53；1H NMR(400 MHz,CDCl3；a mixture of amide rotamers e in a 1:1ratio):δ9.61(t,J＝8.4Hz,2H),8.30(dd,J＝13.2,12.0Hz,2H),7.62–7.58(m,4H),7.48(t,J＝4.8Hz, 2H),7.47–7.42(m,4H),7.37–7.33(m,4H),7.20–7.15(m,2H),6.83–6.77 (m,2H),6.46(d,J＝7.8Hz,1H),6.36(d,J＝7.8Hz,1H),6.22–6.10(m,4H), 6.01(dd,J＝7.8,1.8Hz,1H),5.23(dd,J＝7.8,3.6Hz,1H),4.95(dd,J＝7.8, 3.6Hz,1H),4.89(d,J＝13.8Hz,1H),4.81(d,J＝13.8Hz,1H),4.43–4.40(m, 4H),4.17–4.14(m,1H),3.93–3.90(m,1H),2.81–2.65(m,4H),2.56(dd,J ＝16.8,10.2Hz,2H),2.47(s,3H),2.46(s,3H),2.18(s,3H),2.17(s,3H)；13C NMR(150MHz,CDCl3；all signals for the amide rotamers are listed):δ196.5,196.2,192.7,167.8,167.3,150.7,150.6,145.7,145.4,143.9,143.9,143.6,143.5,134.3,134.3,133.1,132.9,132.7,132.6,131.0,130.1,130.1,129.2,129.1,129.0,129.0,128.3,128.2,127.9,127.9,110.7,110.5,110.3,110.2,46.6,46.6,39.1,37.6,33.1,32.8,28.2,27.5,21.7,21.6；IR(neat):vmax＝2923,1720,1668,1353,1167,753cm–1； HRMS(m/z):[M+Na]+calcd.for C26H26N2NaO5S,501.1454；found,501.1457；[α]D 25＝–43.6 (c0.43,CHCl3)。
化合物III-d的合成
将Ir(dtbbpy)(ppy)2PF6(0.5mg,0.590μmol,0.005equiv.)、KHCO3(59.0mg,0.590mmol, 5.0equiv.)、丙炔酸甲酯(51.2mg,0.610mmol,5.0equiv.)和底物I-m(50.0mg,0.118 mmol,1.0equiv.)置于25mL干燥试管中,抽换氩气保护。混合物用干燥脱气四氢呋喃(5mL) 溶解,35℃下用5W蓝色LED灯照射24h。抽干溶剂,柱层析(异丙醇：环己烷,1:10到1:4, v/v)纯化得III-d(40.1mg),收率67％，III-d-1(13.1mg),收率22％。III-d的dr值(24:1) 通过LC-MS确定:MeCN/H2O,32.5％(0min)→32.5％(6min)→32.5％(14min)→32.5％(15min), 流速(0.4mL/min),保留时间tR1＝11.76min,tR2＝13.14min。
化合物III-d的检测数据如下：TLC(异丙醇：环己烷,1:4v/v):Rf＝0.50；1H NMR(400MHz, CDCl3):δ7.73(d,J＝8.0Hz,1H),7.51(s,1H),7.34–7.30(m,3H),7.18(t, J＝7.6Hz,1H),7.12(d,J＝8.0Hz,2H),7.00(d,J＝7.6Hz,1H),4.26(dd,J＝ 13.2,1.6Hz,1H),4.05–4.01(m,2H),3.82(s,3H),3.44–3.41(m,1H),3.21– 3.15(m,1H),2.96(dd,J＝13.2,3.2Hz,1H),2.91(dd,J＝15.2,8.0Hz,1H),2.49 –2.37(m,3H),2.33(s,3H),2.10(s,3H)；13CNMR(150MHz,CDCl3):δ206.0,170.7, 165.6,144.7,140.6,135.7,133.8,133.4,133.3,129.7,129.7,128.8,127.1,127.1, 126.9,124.2,119.5,65.1,52.9,52.2,44.2,41.2,37.6,35.5,30.2,29.2,21.5；IR (neat):vmax＝3018,1712,1663,1355,1250,744,668cm–1；HRMS(m/z):[M+Na]+calcd. for C27H28N2NaO6S,531.1560；found,531.1555；[α]D 25＝+81.6(c 0.58,CHCl3)。
化合物III-d-1的检测数据如下：TLC(异丙醇：环己烷,1:4v/v):Rf＝0.40；1H NMR(400 MHz,CDCl3):δ7.66(d,J＝8.4Hz,1H),7.56(d,J＝8.0Hz,2H),7.25–7.24(m, 1H),7.17(d,J＝8.0Hz,2H),7.09–7.06(m,2H),6.46(dt,J＝16.0,5.6Hz,1H), 6.20–6.15(m,1H),6.09(d,J＝12.0Hz,1H),6.02(d,J＝16.0Hz,1H),5.75(d, J＝10.0Hz,1H),4.56(dd,J＝17.6,4.4Hz,1H),4.35(d,J＝10.0Hz,1H),3.82 (s,2H),3.77(dd,J＝10.8,4.0Hz,1H),3.73–3.66(m,1H),2.84(dd,J＝16.4, 7.2Hz,1H),2.70(dd,J＝16.0,2.0Hz,1H),2.36(s,3H),2.24(s,3H)；13C NMR(150 MHz,CDCl3):δ198.2,168.5,165.3,144.5,141.5,140.9,139.5,133.7,133.0,132.6, 129.7,129.7,129.0,127.3,127.3,125.4,124.5,124.3,116.0,64.6,59.0,52.1,46.3, 37.7,35.5,27.0,21.5；IR(neat):vmax＝2952,1722,1664,1354,1167,751,578cm–1； HRMS(m/z):[M+Na]+calcd.for C27H28N2NaO6S,531.1560；found,531.1555；[α]D 25＝+90.0 (c 0.17,CHCl3)。
化合物III-e的合成
将Ir(dtbbpy)(ppy)2PF6(0.5mg,0.590μmol,0.005equiv.)、KHCO3(59.0mg,0.590mmol, 5.0equiv.)、1-叔丁基二甲基氧硅烷-3-丁炔-2-酮(58.9mg,0.305mmol,2.5equiv.) 和底物I-m(50.0mg,0.118mmol,1.0equiv.)置于25mL干燥试管中,抽换氩气保护。混合物用干燥脱气四氢呋喃(5mL)溶解,35℃下用5W蓝色LED灯照射24h。抽干溶剂,柱层析(异丙醇：环己烷,1:10到1:4,v/v)纯化得III-e(36.7mg),收率50％，III-e-1(8.1mg),收率11％。19e的dr值(34:1)通过LC-MS确定:MeCN/H2O,40％(0min)→65％(6min)→50％(14min)→40％(15min),流速(0.4mL/min),保留时间tR1＝8.39min,tR2＝8.51min。
化合物III-e的检测数据如下：TLC(丙酮：石油醚,1:1v/v):Rf＝0.40；1H NMR(400MHz, CDCl3):δ7.75–7.72(m,1H),7.41–7.30(m,4H),7.19(t,J＝7.2Hz,1H),7.14 (d,J＝8.4Hz,2H),7.02(d,J＝7.6Hz,1H),4.86(s,2H),4.20(dd,J＝13.2,2.0 Hz,1H),4.08(d,J＝10.4Hz,1H),3.98(t,J＝4.8Hz,1H),3.50–3.45(m,1H), 3.22(q,J＝8.8Hz,1H),3.02(dd,J＝13.2,3.6Hz,1H),2.92(dd,J＝14.8,8.0 Hz,1H),2.44–2.30(m,6H),2.09(s,3H),0.95(s,9H),0.16(s,3H),0.14(s, 3H)；13C NMR(150MHz,CDCl3):δ206.0,196.2,170.6,144.8,140.6,138.6,135.4, 133.7,133.3,129.7,129.7,128.9,127.1,127.1,126.8,124.3,119.3,66.2,65.2,52.5, 44.3,41.3,37.6,35.6,30.1,27.9,25.8,25.8,25.8,21.5,18.4,-5.2,-5.3；IR(neat): vmax＝2927,1714,1357,837,749,577cm-1；HRMS(m/z):[M+Na]+calcd.forC33H42N2NaO6SSi, 645.2425；found,645.2428；[α]D 25＝+40.8(c0.24,CHCl3)。
化合物III-e-1的检测数据如下：TLC(丙酮：石油醚,1:1v/v):Rf＝0.50；1H NMR(400 MHz,CDCl3；a mixture of rotamer e and e’in a 1:1ratio):δ8.48(dd,J＝13.6,11.2Hz,2H),7.62(dd,J＝11.2,8.4Hz,4H),7.50–7.43(m,5H),7.34–7.31 (m,4H),7.20–7.14(m,3H),6.76–6.69(m,2H),6.47(d,J＝7.6Hz,1H),6.36 (d,J＝7.6Hz,1H)，6.17–6.09(m,3H),5.96(dd,J＝7.6,2.0Hz,1H),5.37– 5.26(m,2H),5.21(dd,J＝7.6,3.2Hz,1H),4.93(dd,J＝7.6,3.6Hz,1H),4.33 –4.30(m,4H),4.13–4.09(m,2H),4.05–4.00(m,4H),3.91–3.86(m,2H), 2.78–2.67(m,4H),2.54(dd,J＝16.8,10.8Hz,2H),2.47(s,3H),2.45(s,3H), 2.30(s,3H),2.29(s,3H),0.70(s,18H),0.06––0.15(m,12H)；13C NMR(150MHz,CDCl3；all signals for the amide rotamers are listed):δ198.7,198.6,197.8,167.7, 167.2,145.5,145.3,144.4,144.2,144.0,143.5,140.9,140.9,134.5,134.4,133.0, 132.9,131.9,131.8,130.9,130.1,130.0,129.1,128.9,128.9,128.7,128.2,128.1, 128.0,128.0,110.5,110.3,104.1,103.8,68.4,68.4,46.6,46.5,39.1,37.7,33.1, 32.8,27.2,27.2,25.7,25.6,21.7,21.6,17.9,1.0,–5.6,–5.6,–5.6,–5.6；IR(neat):vmax＝2952,1722,1664,1354,1167,751,578cm–1；HRMS(m/z):[M+Na]+calcd. forC33H42N2NaO6SSi,645.2425；found,645.2418；[α]D 25＝–150.0(c 0.01,CHCl3)。
化合物III-f的合成
将Ir(dtbbpy)(ppy)2PF6(0.6mg,0.614μmol,0.005equiv.)、KHCO3(61.4mg,0.614mmol, 5.0equiv.)、丙炔酸甲酯(51.6mg,0.614mmol,5.0equiv.)和底物I-n(50.0mg,0.122 mmol,1.0equiv.)置于25mL干燥试管中,抽换氩气保护。混合物用干燥脱气四氢呋喃(5mL) 溶解,35℃下用5W蓝色LED灯照射24h。抽干溶剂,柱层析(异丙醇：环己烷,1:10到1:4, v/v)纯化得III-f(30.2mg),收率50％.III-f的dr值(24:1)通过LC-MS确定:MeCN/H2O,32.5％ (0min)→32.5％(6min)→32.5％(14min)→32.5％(15min),流速(0.4mL/min),保留时间 tR1＝11.76min,tR2＝13.14min。
化合物III-f的检测数据如下：TLC(丙酮：石油醚,1:1v/v):Rf＝0.40；1H NMR(400MHz, CDCl3):δ7.75–7.74(m,2H),7.34(t,J＝8.0Hz,3H),7.18(d,J＝7.2Hz,1H),7.14(d,J＝8.0Hz,2H),7.00(d,J＝7.6Hz,1H),4.47(d,J＝13.6Hz,1H),4.23 (d,J＝10.4Hz,1H),4.05(t,J＝10.0Hz,1H),3.89(s,3H),3.25–3.18(m,2H), 3.14(dd,J＝13.6,3.6Hz,1H),2.93(dd,J＝14.8,7.6Hz,1H),2.74–2.68(m, 1H),2.58–2.52(m,1H),2.41(dd,J＝14.8,10.0Hz,1H),2.35(s,3H)；13C NMR (150MHz,CDCl3):δ170.7,165.1,144.7,140.5,136.8,135.2,133.3,130.2,129.7, 129.7,128.9,127.1,127.1,126.9,124.3,119.4,117.4,65.1,53.6,52.5,41.3,37.7, 35.4,30.1,21.5,20.9；IR(neat):vmax＝2952,1713,1669,1256,1167,729,578cm–1； HRMS(m/z):[M+Na]+calcd.for C26H25N3NaO5S,514.1407；found,514.1402；[α]D 25＝+52.8(c 0.11,CHCl3)。
化合物III-g的合成
将Ir(dtbbpy)(ppy)2PF6(0.4mg,0.483μmol,0.005equiv.)、KHCO3(48.3mg,0.483mmol, 5.0equiv.)、丙炔酸甲酯(40.3mg,0.483mmol,5.0equiv.)和底物I-o(50.0mg,0.097 mmol,1.0equiv.)置于25mL干燥试管中,抽换氩气保护。混合物用干燥脱气四氢呋喃(5mL) 溶解,35℃下用5W蓝色LED灯照射24h。抽干溶剂,柱层析(石油醚：乙酸乙酯,5:1到1:1, v/v)纯化得III-g(20.9mg),收率36％，III-g-1-Z(13.4mg),收率23％，III-g-1-E(12.2mg), 收率21％。III-g的dr值(45:1)通过LC-MS确定:MeCN/H2O,35％(0min)→40％(6min)→35％ (14min)→35％(15min),流速(0.4mL/min),保留时间tR1＝5.84min,tR2＝7.13min。
化合物III-g的检测数据如下：TLC(石油醚:乙酸乙酯,1:1v/v):Rf＝0.57；1H NMR(600 MHz,CDCl3):δ7.73(d,J＝8.4Hz,1H),7.54(s,1H),7.35–7.32(m,3H),7.19 (t,J＝7.2Hz,1H),7.13(d,J＝7.8Hz,2H),7.01(d,J＝7.2Hz,1H),4.58(d, J＝12.6Hz,1H),4.14–4.01(m,6H),3.86(s,3H),3.36–3.30(m,1H),3.18(q, J＝8.4Hz,1H),2.97(d,J＝12.6Hz,1H),2.91(dd,J＝14.4,7.8Hz,1H),2.40 (dd,J＝14.4,10.2Hz,1H),2.34(s,3H),1.85–1.70(m,2H),1.31–1.25(m, 6H)；13C NMR(150MHz,CDCl3):δ170.5,165.4,144.7,140.6,135.7,134.1,133.7, 133.4,129.7,129.7,128.8,127.1,127.1,126.9,124.3,119.6,65.1,61.8,52.8,52.3, 41.6,37.6,35.5,29.6,28.7,27.8,26.8,21.5,16.3；IR(neat):vmax＝2925,1716, 1663,1236,1167,753,670cm–1；HRMS(m/z):[M+Na]+calcd.forC29H35N2NaO8PS,625.1743； found,625.1740；[α]D 25＝+40.8(c 0.07,CHCl3)。
化合物III-g-1-Z的检测数据如下：TLC(石油醚:乙酸乙酯,1:1v/v):Rf＝0.34；1HNMR (600MHz,CDCl3):δ7.69(d,J＝8.0Hz,1H),7.51(d,J＝7.8Hz,2H),7.28–7.05 (m,1H),7.16(d,J＝7.8Hz,2H),7.08(t,J＝7.8Hz,1H),7.04(d,J＝7.2Hz, 1H),6.53–6.40(m,1H),6.17(t,J＝10.8Hz,1H),6.08(d,J＝11.4Hz,1H),5.69 (d,J＝10.2Hz,1H),5.50–5.43(m,1H),4.38–4.29(m,2H),4.10–3.95(m, 4H),3.87–3.85(m,1H),3.81(s,3H),3.57–3.55(m,1H),2.80(dd,J＝16.8, 7.2Hz,1H),2.71(d,J＝16.2Hz,1H),1.36(t,J＝7.2Hz,3H),1.28(t,J＝7.2 Hz,3H)；13C NMR(150MHz,CDCl3):δ168.5,165.3,146.7,146.6,144.4,141.5,139.9, 133.5,129.6,129.6,129.0,127.2,127.2,125.6,124.3,124.0,118.4,117.0,64.7, 61.8,61.7,59.3,51.9,47.6,47.4,37.6,34.9,21.5,16.3；IR(neat):vmax＝2925,1716,1663,1236,1167,753,670cm–1；HRMS(m/z):[M+Na]+calcd.for C29H35N2NaO8PS,625.1743；found,625.1740；[α]D 25＝+117.0(c 0.09,CHCl3)。
化合物III-g-1-E的检测数据如下：TLC(石油醚:乙酸乙酯,1:1v/v):Rf＝0.40；1HNMR (600MHz,CDCl3):δ7.73(d,J＝8.4Hz,1H),7.56(d,J＝8.4Hz,2H),7.29(t, J＝7.2Hz,1H),7.21(d,J＝8.2Hz,2H),7.09–6.99(m,3H),6.49–6.41(m, 1H),5.95(dd,J＝15.2,1.8Hz,1H),5.43(t,J＝17.4Hz,1H),4.68–4.63(m, 2H),4.46(d,J＝10.2Hz,1H),4.03–3.91(m,2H),3.80(s,3H),3.70–3.63(m, 1H),3.59–3.50(m,1H),2.37(s,3H),1.37(t,J＝7.2Hz,3H),1.26(t,J＝7.2 Hz,3H)；13C NMR(150MHz,CDCl3):δ168.8,165.7,145.7,144.7,143.9,141.4,133.5, 132.2,129.9,129.9,129.2,127.1,127.1,125.5,124.2,122.5,119.2,116.2,65.3, 63.8,61.9,61.8,52.0,48.5,48.4,38.4,34.8,21.5,16.3；IR(neat):vmax＝2984, 1723,1670,1355,1166,1023,966,748,665cm–1；HRMS(m/z):[M+Na]+calcd.forC29H35N2NaO8PS,625.1743；found,625.1740；[α]D 25＝+54.0(c 0.07,CHCl3)。
化合物III-h的合成
将Ir(dtbbpy)(ppy)2PF6(0.4mg,0.483μmol,0.005equiv.)、KHCO3(46.6mg,0.466mmol, 5.0equiv.)、丙炔酸甲酯(39.2mg,0.466mmol,5.0equiv.)和底物I-p(50.0mg,0.093 mmol,1.0equiv.)置于25mL干燥试管中,抽换氩气保护。混合物用干燥脱气二氧六环(5mL) 溶解,35℃下用5W蓝色LED灯照射24h。抽干溶剂,柱层析(石油醚：丙酮,1:3v/v)纯化得19h(38.9mg),收率76％。III-h的dr值(45:1)通过LC-MS确定:MeCN/H2O,30％(0min)→40％ (6min)→30％(14min)→30％(15min),流速(0.4mL/min),保留时间tR1＝9.94min,tR2＝ 11.89min。
化合物III-h的检测数据如下：TLC(石油醚:丙酮,3:1v/v):Rf＝0.45；1H NMR(400MHz, CDCl3):δ7.74(d,J＝8.0Hz,1H),7.63(d,J＝1.6Hz,1H),7.37–7.25(m,3H),7.19(t,J＝7.6Hz,1H),7.13(d,J＝7.6Hz,2H),7.00(d,J＝7.2Hz,1H),5.76 –5.63(m,1H),5.02–4.90(m,2H),4.42(d,J＝12.4Hz,1H),4.10–3.93(m,2H), 3.85(s,3H),3.77–3.60(m,1H),3.17(q,J＝9.2Hz,1H),3.01(dd,J＝12.8, 3.6Hz,1H),2.90(dd,J＝14.8,8.0Hz,1H),2.41–2.32(m,1H),2.34(s,3H)；13C NMR(150MHz,CDCl3):δ170.3,165.6,144.7,140.7,135.9,135.4,133.9,133.5, 132.4,129.7,129.7,128.9,127.2,127.2,127.0,124.3,119.7,115.9,65.2,52.9, 52.3,42.0,37.6,36.9,35.4,21.6；IR(neat):vmax＝2924,1716,1666,1356,1257, 1169,1090,760,579cm–1；HRMS(m/z):[M+Na]+calcd.for C26H26N2NaO5S,501.1455；found, 501.1453；[α]D 20＝+139.3(c 0.27,CHCl3)。
化合物III-i的合成：参考III-a的合成方法
1H),6.95(d,J＝7.8Hz,1H),6.82–6.78(m,1H),6.02(dd,J＝9.6,2.4Hz,1H), 4.15–4.07(m,2H),3.49–3.42(m,1H),3.12–3.05(m,2H),2.90–2.85(m,1H), 2.77–2.70(m,2H),2.67(t,J＝12.6Hz,1H),2.53–2.46(m,2H),2.35(s,3H), 2.24(dd,J＝19.8,5.4Hz,1H),1.71–1.64(m,1H)；13C NMR(150MHz,CDCl3):δ 198.0,170.5,146.8,144.3,141.2,135.9,134.7,129.7,129.7,129.5,128.6,127.1, 127.1,126.3,123.5,119.3,66.6,53.0,43.5,43.5,36.4,33.6,33.1,29.4,29.3, 21.6；IR(neat):vmax＝2921,2851,1649,1460,1354,1259,1165,1089,1016,797,754 cm–1；HRMS(m/z):[M+Na]+calcd.for C26H26N2NaO4S,485.1505；found,485.1505；[α]D 20＝+40.3(c 0.32,CHCl3)；m.p.:252–253C.
6.94–6.90(m,1H),6.10(dd,J＝9.6,2.4Hz,1H),4.13(dd,J＝ 13.2,4.8Hz,1H),4.04(t,J＝9.6Hz,1H),3.60(dt,J＝9.6,6.0Hz,1H),3.13 (q,J＝6.0Hz,1H),2.98(t,J＝12.6Hz,1H),2.85–2.75(m,2H),2.53–2.43(m, 2H),2.40–2.35(m,1H),2.34(s,3H),2.29–2.17(m,2H),2.10–2.01(m,1H)；13C NMR(150MHz,CDCl3):δ198.1,171.8,147.1,144.4,141.0,135.9,134.1,129.9,129.6, 129.6,128.7,127.1,127.1,126.5,124.1,119.4,64.9,52.1,45.6,43.6,37.2,36.4, 34.9,30.8,22.7,21.5；IR(neat):vmax＝2922,1659,1259,1167,1015,795,671,579 cm–1；HRMS(m/z):[M+Na]+calcd.for C26H26N2NaO4S,485.1505；found,485.1504；[α]D 20＝+41.9(c 0.41,CHCl3)；m.p.:161–163C.
2.4Hz,1H),4.48(dd,J＝12.8,4.0Hz,1H),4.27(dd,J＝10.0,2.0Hz,1H),3.79 (d,J＝13.2Hz,1H),3.35(t,J＝7.6Hz,1H),2.75(dd,J＝17.2,2.4Hz,1H),2.67 (d,J＝13.6Hz,1H),2.59(dd,J＝17.2,3.4Hz,1H),2.46–2.33(m,6H),2.14 –2.02(m,1H),2.00–1.87(m,1H),1.45(q,J＝24.8,13.2Hz,1H)；13C NMR(150 MHz,CDCl3):δ198.6,168.4,148.1,144.4,141.4,134.6,133.8,129.8,129.8,129.3, 128.6,126.9,126.9,125.5,123.5,117.1,64.1,63.0,49.7,49.1,37.7,37.1,32.0, 30.9,29.7,21.5；IR(neat):vmax＝2923,1648,1460,1350,1261,1166,1091cm–1；HRMS (m/z):[M+H]+calcd.for C26H27N2O4S,463.1686；found,463.1686；[α]D 20＝+105.2(c 0.51, CHCl3)；m.p.:232–234C.
Hz,1H),4.18(dd,8.4,6.0Hz,1H),3.47–3.42(m,1H),3.13–3.08(m,1H),2.74 –2.70(m,2H),2.66(dd,J＝14.4,3.6Hz,1H),2.56(dt,J＝12.6,4.2Hz,1H), 2.45–2.37(m,2H),2.35(s,3H),2.33–2.29(m,2H),1.69(dd,J＝25.8,12.6Hz, 1H)；13C NMR(150MHz,CDCl3):δ199.7,169.7,149.2,144.4,141.0,135.5,134.9, 129.8,129.8,128.8,128.5,126.9,126.9,126.2,123.4,119.0,64.9,58.8,46.3,46.0, 37.0,32.8,31.2,29.6,25.7,21.6；IR(neat):vmax＝2962,2920,1666,1260,1091, 1019cm–1；HRMS(m/z):[M+Na]+calcd.forC26H26N2NaO4S,485.1505；found,485.1503；[α]D 25＝+17.9(c 0.26,CHCl3)；m.p.:120–122℃.
化合物III-k的合成：参考III-a的合成方法
(m,1.7H),7.18–7.09(m,5.1H),6.97–6.92(m,1.7H),5.57(q, J＝6.6Hz,0.7H),5.50(q,J＝7.2Hz,1H),5.24–5.07(m,3.4H),4.92(d,J＝ 14.4Hz,1H),4.41–4.48(d,J＝15.6Hz,0.7H),4.12(t,J＝9.6Hz,1H),4.07 –3.96(m,1.7H),3.70(m,1H),3.62(m,1.7H),3.40–3.32(m,1H),3.32–3.25 (m,0.7H),3.17–3.03(m,1.7H),2.86(dd,J＝15.6,8.4Hz,1H),2.82–2.70 (m,1.7H),2.69–2.62(m,1.1H),2.42–2.26(m,1.7H),2.35(s,3H),2.34(s,2.1H),2.15(dd,J＝15.0,9.0Hz,1H),1.68(d,J＝6.6Hz,2.1H),1.63(d,J＝6.6 Hz,3H)；13CNMR(150MHz,CDCl3):δ172.8,169.6,168.9,144.5,144.4,140.9,140.9, 136.4,136.4,135.8,135.7,133.9,133.8,129.6,129.6,129.5,129.1,128.6,128.5, 128.5,128.2,128.2,128.1,128.1,127.2,127.2,126.6,126.6,124.5,124.1,124.1, 123.8,119.5,119.4,66.7,66.6,66.5,65.9,53.8,51.9,44.9,42.9,38.4,37.3,36.7, 36.6,34.9,34.8,28.8,27.4,21.6,13.5,13.3；IR(neat):vmax＝2916,1731,1658, 1356,1168cm–1；HRMS(m/z):[M+Na]+calcd.for C32H32N2NaO5S,579.1924；found, 579.1917.
4.63(d,J＝13.8Hz,1H),4.28(d,J＝14.4Hz,0.5H),4.14–4.06(m,1H),4.01 –3.92(m,1H),3.77–3.69(m,1.5H),3.62–3.55(m,0.5H),3.46(dd,J＝12.0, 5.4Hz,1H),3.35–3.26(m,1H),3.15–3.03(m,1.5H),2.95–2.83(m,2H),2.77 (dd,J＝15.0,8.4Hz,0.5H),2.68–2.60(m,0.5H),2.47(dt,J＝15.0,6.6Hz, 0.5H),2.39–2.30(m,0.5H),2.35(s,3H),2.34(s,1.5H),2.27(dd,J＝15.6,9.6 Hz,1.5H),2.17(dd,J＝15.0,9.0Hz,0.5H),1.89–1.81(m,0.5H),1.63(d,J＝ 6.6Hz,1.5H),1.48(d,J＝6.6Hz,3H)；13C NMR(150MHz,CDCl3):δ172.6,172.5, 169.0,168.5,144.5,140.9,136.8,136.3,135.7,133.8,133.7,130.0,129.6,129.6, 128.6,128.6,128.5,128.5,128.3,128.2,128.2,128.1,127.7,127.2,127.1,127.0, 126.7,126.7,126.6,125.5,124.1,124.1,119.6,119.6,68.0,66.8,66.7,65.7,53.1, 52.3,44.1,44.1,41.3,38.5,37.0,36.4,35.0,34.9,29.2,26.8,25.6,21.6,13.4,13.3；IR(neat):vmax＝2922,1730,1657,1477,1459,1355,1168cm–1；HRMS(m/z):[M +Na]+calcd.for C32H32N2NaO5S,579.1924；found,579.1913.
化合物III-l的合成：参考III-a的合成方法
–5.73(m,1H),5.72–5.62(m,1H),5.61–5.51(m,3H),5.17–5.07(m,17H), 5.07–4.98(m,9H),4.38–4.23(m,6H),4.22–4.15(m,5H),4.04–3.92(m, 1H),3.56(td,J＝10.0,3.6Hz,1H),3.51–3.36(m,6H),3.22(dd,J＝9.6,3.6 Hz,1H),3.18–3.02(m,6H),2.99–2.89(m,2H),2.89–2.77(m,5H),2.76–2.48 (m,28H),2.38–2.21(m,27H),2.09–1.98(m,3H),1.89–1.70(m,8H),1.29 –1.16(m,2H),0.90(t,J＝7.6Hz,1H)；13C NMR(150MHz,CDCl3):δ174.3,173.1, 172.2,169.5,168.2,168.0,144.4,144.4,140.9,140.9,140.9,138.1,136.5,136.4, 135.7,135.6,135.2,134.9,134.8,134.7,134.0,133.8,129.7,129.6,128.6,128.2, 128.4,128.3,128.1,127.9,127.1,126.9,126.9,126.7,126.2,126.1,125.9,124.0, 123.5,119.6,119.0,118.5,118.0,117.3,116.1,77.2,77.0,76.8,66.6,66.5,66.5, 66.2,65.2,64.8,58.7,58.0,51.1,46.5,45.8,45.3,44.3,41.2,40.6,40.3,39.8,39.6,37.1,37.0,36.5,34.7,32.9,31.9,31.7,28.3,26.5,21.5；IR(neat):vmax＝ 1729,1651,1496,1455,1354,1265,1163cm-1；HRMS(m/z):[M+Na]+calcd.for C32H32N2NaO5S,579.1924；found,579.1925.
2H),3.63(td,J＝9.2,4.4Hz,1H),3.14–2.96(m,3H),2.73(dd,J＝16.4,8.4 Hz,1H),2.57(m,2H),2.37(dd,J＝16.4,6.8Hz,1H),2.29(s,3H),2.10–2.00 (m,1H)；13C NMR(150MHz,CDCl3):δ172.5,169.9,136.2,134.3,129.6,128.4,128.2, 128.2,127.0,126.5,123.7,119.3,117.1,66.3,66.1,51.9,51.9,42.3,40.6,40.5, 40.0,36.3,33.4,29.8,21.5；IR(neat):vmax＝2924,1728,1655,1597,1165cm-1；HRMS (m/z):[M+Na]+calcd forC32H32N2NaO5S,579.1924；found,579.1923；[α]D 25＝+45.4(c 2.42,CHCl3).
实施例8：化合物IV的制备
以化合物IV-a的制备为例进行说明：
氩气保护下，将Ir(dtbbpy)(ppy)2PF6(0.5mg,0.579μmol,0.005equiv.)、KHCO3(57.9mg, 0.579mmol,5.0equiv.)、丙烯酸甲脂(11.5L,0.130mmol,1.1equiv.)和底物I-b(50.0 mg,0.116mmol,1.0equiv.)置于10mL干燥试管中，混合物用干燥脱气四氢呋喃(5mL)溶解，35℃下用5W蓝色LED灯照射15h。抽干溶剂，柱层析(石油醚：丙酮，2:1，v/v)纯化得IV-a(50mg)，收率83％。
7.08–7.03(m,2H),6.93(d,J＝6.8Hz,2H),5.06(d,J＝14.4 Hz,1H),4.22(d,J＝10.4Hz,1H),3.92(d,J＝14.8Hz,1H),3.86(dd,J＝9.2,6.0 Hz,1H),3.74(s,3H),3.68–3.60(m,1H),2.82(dd,J＝16.0,6.0Hz,1H),2.73 (dd,J＝16.0,2.0Hz,1H),2.52(t,J＝7.2Hz,2H),2.33(s,3H),2.11–1.84(m, 2H)；13C NMR(150MHz,CDCl3):δ173.2,168.5,144.2,141.6,136.4,134.1,132.6, 129.7,129.7,128.5,128.5,128.5,128.4,128.4,127.4,126.9,126.9,125.0,124.1, 116.1,62.7,62.6,52.0,49.4,38.1,34.4,30.7,28.2,21.5；IR(neat):vmax＝2924, 1733,1657,1353,1166,666,578cm–1；HRMS(m/z):[M+Na]+calcd.forC29H30N2NaO5S, 541.1768；found,541.1759；[α]D 25＝+77.9(c 0.29,CHCl3).
2H),7.07–7.08(m,2H),6.98(d,J＝7.2Hz,2H),4.87(d,J＝14.4Hz,1H),4.30 (d,J＝10.0Hz,1H),4.09(d,J＝14.4Hz,1H),3.90(dd,J＝9.6,4.8Hz,1H),3.72 –3.68(m,1H),2.80–2.68(m,2H),2.48–2.44(m,2H),2.34(s,3H),2.09– 2.00(m,1H),1.89–1.80(m,1H)；13C NMR(150MHz,CDCl3):δ168.1,144.5,141.4, 136.1,133.8,132.1,129.8,129.8,128.7,128.7,128.7,128.5,128.5,127.8,127.0, 127.0,125.2,124.2,119.0,115.9,62.6,62.5,49.8,38.0,34.4,29.5,21.5,14.8； IR(neat):vmax＝2925,1656,1351,1165,665,578cm–1；HRMS(m/z):[M+Na]+calcd. for C28H27N3NaO3S,508.1665；found,508.1660；[α]D 25＝+92.4(c 0.38,CHCl3).
6.91(d,J＝7.2Hz,2H),5.01(d,J＝14.4Hz,1H),4.22(d,J＝10.0 Hz,1H),3.98(d,J＝14.4Hz,1H),3.71(dd,J＝10.0,4.8Hz,1H),3.66–3.56 (m,1H),2.82(dd,J＝16.0,6.0Hz,1H),2.72(dd,J＝16.0,2.0Hz,1H),2.69– 2.53(m,2H),2.33(s,3H),2.21(s,3H),2.07–1.91(m,1H),1.84–1.77(m,1H)；13C NMR(100MHz,CDCl3):δ207.6,168.4,144.2,141.6,136.5,134.1,132.7,129.7, 129.7,128.4,128.4,128.4,128.4,128.4,127.4,126.8,126.8,125.1,124.1,116.1, 62.9,62.8,49.2,39.9,38.1,34.2,30.1,26.4,21.5；IR(neat):vmax＝2924,1654, 1350,1164,665,578cm–1；HRMS(m/z):[M+Na]+calcd.forC29H30N2NaO4S,525.1819；found, 525.1811；[α]D 25＝+84.4(c 0.83,CHCl3).
–7.03(m,2H),6.92(d,J＝6.8Hz,2H),5.01(d,J＝14.4Hz,1H),4.20(d,J＝ 10.4Hz,1H),3.99(d,J＝14.8Hz,1H),3.77(dd,J＝10.0,4.8Hz,1H),3.70– 3.58(m,1H),2.81(dd,J＝16.0,6.0Hz,1H),2.77–2.61(m,3H),2.33(s,3H), 2.09–1.94(m,1H),1.91–1.79(m,1H)；13CNMR(150MHz,CDCl3):δ200.7,168.4, 144.3,141.6,136.4,134.1,132.6,129.8,129.8,128.5,128.5,128.5,128.4,128.4, 127.5,126.9,126.9,125.1,124.1,116.1,62.8,62.7,49.3,40.7,38.1,34.2,25.0, 21.5；IR(neat):vmax＝2924,1655,1351,1165,664,577cm–1；HRMS(m/z):[M+Na]+ calcd.for C28H28N2NaO4S,511.1662；found,511.1658；[α]D 25＝+95.5(c 0.6,CHCl3).
7.30(d,J＝8.4Hz,2H),7.21(m,4H),7.12–7.05(m,2H),7.04–6.98(m,4H), 4.95(d,J＝14.4Hz,1H),4.21(d,J＝10.2Hz,1H),4.13(d,J＝14.4Hz,1H),3.91 (dd,J＝10.4,5.6Hz,1H),3.72–3.62(m,1H),3.17(q,J＝6.4Hz,2H),2.95(dd, J＝16.0,6.3Hz,1H),2.75(d,J＝16.0Hz,1H),2.34–2.21(m,4H),1.97–1.90 (m,1H)；13C NMR(150MHz,CDCl3):δ199.0,168.7,144.2,141.7,136.7,136.5,133.9, 133.5,132.9,129.6,129.6,128.7,128.7,128.5,128.5,128.5,128.5,128.5,128.1, 128.1,127.5,126.9,126.9,125.1,124.2,116.1,63.2,62.9,49.7,38.2,35.2,34.6, 26.5,21.5；IR(neat):vmax＝2923,1656,1352,1165,665,578cm–1；HRMS(m/z):[M +Na]+calcd.for C34H32N2NaO4S,587.1975；found,587.1965；[α]D 25＝+31.7(c 0.4,CHCl3).
6.94(d,J＝6.4z,2H),4.91(d,J＝14.4Hz,1H),4.36(d,J＝10.0Hz,1H),4.09 (d,J＝14.4Hz,1H),3.78(dd,J＝10.4,4.8Hz,1H),3.71–3.56(m,1H),3.00 (s,6H),2.90(dd,J＝16.0,6.0Hz,1H),2.72(d,J＝16.0Hz,1H),2.45(t,J＝ 6.8Hz,2H),2.32(s,3H),2.25–2.11(m,1H),1.86–1.77(m,1H)；13C NMR(150 MHz,CDCl3):δ171.8,168.8,144.2,141.7,136.8,134.1,133.1,129.7,129.7,128.4, 128.4,128.4,128.4,128.4,127.3,126.9,126.9,125.1,124.2,116.1,63.6,62.8, 49.5,38.2,37.1,35.7,34.4,30.0,27.8,21.5；IR(neat):vmax＝2924,1644,1352, 1166,666,579cm–1；HRMS(m/z):[M+Na]+calcd.forC30H33N3NaO4S,554.2084；found, 554.2092；[α]D 25＝+63.0(c 0.37,CHCl3).
2H),6.90(d,J＝7.2Hz,2H),5.09(d,J＝14.4Hz,1H),4.25(d,J＝8.0Hz,1H), 4.20(d,J＝10.0Hz,2H),3.93(d,J＝14.8Hz,1H),3.74(dd,J＝10.4,5.2Hz, 1H),3.64–3.60(m,1H),2.86–2.64(m,4H),2.32(s,3H),2.06–1.93(m,1H), 1.91–1.85(m,1H),0.96(s,9H),0.13(d,J＝5.6Hz,6H)；13C NMR(150MHz,CDCl3): δ210.2,168.6,144.2,141.6,136.5,134.2,132.6,129.7,129.7,128.5,128.5,128.5, 128.4,128.4,127.4,126.9,126.9,125.1,124.1,116.1,69.3,62.8,62.7,49.2,38.1, 35.0,34.2,26.0,25.8,25.8,25.8,21.5,18.3,–5.4,–5.5；IR(neat):vmax＝2856, 1658,1353,1165,665,578cm–1；HRMS(m/z):[M+Na]+calcd.for C35H44N2NaO5SSi,655.2620； found,655.2622；[α]D 25＝+93.6(c 0.87,CHCl3).
J＝6.8Hz,2H),4.91(d,J＝14.4Hz,1H),4.27(d,J＝10.4Hz,1H), 4.19–3.96(m,5H),3.85(dd,J＝9.2,5.2Hz,1H),3.71–3.58(m,1H),2.84– 2.64(m,2H),2.33(s,3H),2.09–1.67(m,4H),1.33(dt,J＝11.2,7.2Hz,6H)；13C NMR(150MHz,CDCl3):δ168.4,144.3,141.6,136.4,134.0,132.6,129.7,129.7, 128.5,128.5,128.5,128.4,128.4,127.5,127.0,127.0,125.1,124.1,116.1,63.8, 63.6,62.6,61.9,49.9,38.0,34.3,26.3,23.2,22.3,21.5,16.5；IR(neat):vmax＝ 2924,1657,1230,1166,730,665,578cm–1；HRMS(m/z):[M+H]+calcd.for C31H37N2O6- PS,597.2176；found,597.2183；[α]D 25＝+45.5(c 0.73,CHCl3).
6.99(d,J＝6.4Hz,2H),6.09(dd,J＝11.6,10.0Hz,1H),5.98(d,J＝11.6Hz, 1H),5.69(d,J＝10.0Hz,1H),4.89(d,J＝14.8Hz,1H),4.27(dd,J＝14.4,2.0 Hz,1H),4.16(d,J＝14.4Hz,1H),3.77(s,3H),3.56(dd,J＝9.6,7.2Hz,1H), 2.84(dd,J＝16.0,6.4Hz,1H),2.74(dd,J＝16.0,3.2Hz,1H),2.32(s,3H)；13C NMR(100MHz,CDCl3):δ168.6,165.4,144.1,141.6,140.3,136.6,134.0,133.1,129.6, 129.6,128.5,128.3,128.3,128.3,128.3,127.3,127.2,127.2,125.3,123.9,123.7, 116.8,64.9,58.8,51.9,48.5,37.8,35.1,21.5；IR(neat):vmax＝2928,1724,1660, 1356,1168,667,579cm–1；HRMS(m/z):[M+Na]+calcd.for C29H28N2NaO5S,539.1611；found, 539.1607；[α]D 25＝+89.8(c 0.89,CHCl3).
7.07(d,J＝4.2Hz,2H),6.97(dd,J＝16.0,4.2Hz,1H),6.94(d,J＝7.2Hz,2H), 5.90(d,J＝16.0Hz,1H),5.17(d,J＝14.4Hz,1H),4.69(s,1H),4.38(d,J＝10.2 Hz,1H),3.83(d,J＝15.0Hz,1H),3.78(s,3H),3.65–3.62(m,1H),2.74–2.59 (m,2H),2.34(s,3H)；13C NMR(150MHz,CDCl3):δ168.9,166.0,144.5,144.4,141.5, 135.8,134.0,132.1,129.8,129.8,128.7,128.6,128.6,128.6,128.6,127.8,127.0, 127.0,125.2,124.2,122.1,115.9,63.9,63.5,52.0,49.4,38.6,34.9,21.5；IR(neat): vmax＝2923,1722,1667,1356,1167,666,579cm–1；HRMS(m/z):[M+Na]+calcd.for C29H28N2NaO5S,539.1611；found,539.1612；[α]D 25＝+56.2(c 2.87,CHCl3).
2H),7.42(d,J＝8.4Hz,1H),7.23–7.18(m,4H),7.14(d,J＝7.8Hz,2H),7.07 –7.03(m,4H),6.26(d,J＝11.4Hz,1H),5.88(dd,J＝11.4,10.2Hz,1H),5.49 (dd,J＝9.6,3.0Hz,1H),4.69(d,J＝14.4Hz,1H),4.44(d,J＝14.4Hz,1),4.31 (dd,J＝9.6,3.0Hz,1H),3.57–3.49(m,1H),2.84(dd,J＝16.2,7.2Hz,1H), 2.70(dd,J＝16.2,3.6Hz,1H),2.33(s,3H),2.23(s,3H)；13C NMR(150MHz,CDCl3): δ198.6,168.8,144.1,141.6,137.7,137.0,134.1,133.4,131.0,129.6,129.6,128.6, 128.4,128.4,128.3,128.3,127.3,127.3,127.2,125.3,124.0,116.9,65.2,58.3, 48.5,37.7,35.4,31.3,21.5；IR(neat):vmax＝2923,1657,1460,1353,1167,719, 666cm–1；HRMS(m/z):[M+Na]+calcd.for C29H28N2NaO4S,523.1662；found,523.1656；[α]D 25＝+58.3(c 0.17,CHCl3).
(dd,J＝16.2,4.2Hz,1H),6.09(dd,J＝16.2,2.4Hz,1H),5.00(d,J＝14.4Hz,1H), 4.74(s,1H),4.40(d,J＝10.2Hz,1H),4.04(d,J＝14.4Hz,1H),3.65(t,J＝7.8 Hz,1H),2.69(dd,J＝15.6,1.8Hz,1H),2.63(dd,J＝15.6,6.6Hz,1H),2.35(s, 3H),2.23(s,3H)；13C NMR(100MHz,CDCl3):δ197.0,168.9,144.5,142.3,141.5, 136.0,133.9,132.1,130.1,129.9,129.9,128.8,128.7,128.7,128.7,128.7,127.8, 127.0,127.0,125.2,124.2,115.9,64.0,63.7,49.7,38.5,35.0,28.6,21.5；IR(neat): vmax＝2923,1663,1355,1166,1021,800,578cm–1；HRMS(m/z):[M+Na]+calcd.for C29H28N2NaO4S,523.1662；found,523.1667；[α]D 25＝+28.7(c 0.23,CHCl3).
4H),7.13(d,J＝8.0Hz,2H),7.05(q,J＝6.8Hz,4H),6.55(d,J＝12.0Hz,1H), 6.04(dd,J＝11.6,9.6Hz,1H),5.56(dd,J＝9.6,2.4Hz,1H),4.69(d,J＝14.4 Hz,1H),4.45(d,J＝14.4Hz,1H),4.33(dd,J＝9.6,3.2Hz,1H),4.23(d,J＝1.6 Hz,2H),3.57–3.48(m,1H),2.86(dd,J＝16.0,6.8Hz,1H),2.69(dd,J＝16.0, 3.6Hz,1H),2.33(s,3H),0.94(s,9H),0.12(s,6H)；13C NMR(150MHz,CDCl3):δ 200.1,168.9,144.1,141.6,140.1,137.1,134.2,133.4,129.6,129.6,128.5,128.3, 128.3,128.3,128.3,127.3,127.3,127.2,126.6,125.3,124.0,117.0,69.7,65.1, 58.5,48.5,37.7,35.5,25.8,25.8,25.8,21.5,18.3,–5.4,–5.4；IR(neat):vmax＝2928,1662,1359,1168,838,665,579cm–1；HRMS(m/z):[M+Na]+calcd.for C35H42N2NaO5SSi,653.2476；found,653.2474；[α]D 25＝+75.2(c 0.41,CHCl3).
2H),7.07(d,J＝4.4Hz,2H),6.98–6.90(m,3H),6.41(dd,J＝16.0,2.0Hz,1H), 5.08(d,J＝14.4Hz,1H),4.74(s,1H),4.39(d,J＝10.4Hz,1H),4.26(s,2H), 3.94(d,J＝14.8Hz,1H),3.63(dd,J＝10.0,4.0Hz,1H),2.71–2.56(m,2H),2.34 (s,3H),0.94(s,9H),0.11(s,6H)；13C NMR(100MHz,CDCl3):δ198.0,168.8,144.5, 142.9,141.5,136.0,133.9,132.1,129.8,129.8,128.7,128.6,128.6,128.6,128.6, 127.8,127.0,127.0,125.2,124.9,124.2,115.9,69.1,63.9,49.6,40.0,38.6,35.0, 25.8,25.8,25.8,21.5,18.3,–5.40,–5.40；IR(neat):vmax＝2927,1668,1358,1258, 1167,1019,800,666,578cm–1；HRMS(m/z):[M+Na]+calcd.for C35H42N2NaO5SSi,653.2476； found,653.2470；[α]D 25＝+20.5(c 0.21,CHCl3).
＝7.8Hz,1H),6.37(d,J＝7.8Hz,1H),6.17(d,J＝7.8Hz,1H),6.06(d,J＝7.8 Hz,1H),5.35(d,J＝13.2Hz,1H),5.24(d,J＝13.2Hz,1H),5.12(dd,J＝7.8, 3.6Hz,1H),4.90(dd,J＝7.8,3.6Hz,1H),4.84(d,J＝15.0Hz,2H),4.60(t,J ＝13.8Hz,2H),4.09–3.99(m,5H),3.82–3.77(m,1H),2.81–2.74(m,2H), 2.66(dd,J＝16.2,8.4Hz,1H),2.51(dd,J＝16.8,9.0Hz,1H),2.46(s,3H),2.43 (s,3H),0.72(s,9H),0.68(s,9H),–0.04(d,J＝9.0Hz,6H),–0.10(d,J＝9.0 Hz,6H)；13C NMR(150MHz,CDCl3):δ198.7,198.5,167.8,167.2,145.5,145.3,144.5, 144.2,144.1,143.8,136.9,136.9,134.6,134.5,132.8,132.7,130.9,130.1,130.0, 129.5,129.3,129.3,129.1,129.0,128.8,128.7,128.1,128.1,128.1,128.0,128.0, 127.7,127.7,109.9,109.8,104.2,103.9,68.6,68.5,49.1,49.1,39.3,37.9,33.0, 32.7,25.7,25.6,21.7,21.7,18.0,18.0,–5.6,–5.6,–5.7,–5.7；IR(neat):vmax＝2927,2855,1672,1572,1370,1171,1079,838,663cm–1；HRMS(m/z):[M+Na]+calcd.for C35H42N2NaO5SSi,653.2476；found,653.2468.
(d,J＝7.8Hz,2H),7.42(d,J＝8.4Hz,1H),7.19–7.17(m, 4H),7.09(d,J＝8.4Hz,2H),7.05–7.03(m,4H),6.85(d,J＝11.4Hz,1H),6.08 (dd,J＝11.4,9.0Hz,1H),5.37(d,J＝8.4Hz,1H),4.64(d,J＝14.4Hz,1H),4.51 (d,J＝14.4Hz,1H),4.33(dd,J＝10.2,2.4Hz,1H),3.57(t,J＝7.2Hz,1H),2.90 (dd,J＝15.6,7.2Hz,1H),2.68(d,J＝16.2Hz,1H),2.31(s,3H)；13C NMR(150MHz, CDCl3):δ191.6,169.0,144.1,141.6,138.4,137.0,136.9,133.8,133.6,133.3,129.6, 129.5,129.5,128.9,128.9,128.7,128.7,128.6,128.5,128.5,128.4,128.4,127.3, 127.3,127.3,125.2,124.1,116.7,65.3,59.2,49.0,37.7,36.0,21.5；IR(neat): vmax＝2923,1659,1356,1226,1164,731,665,578cm–1；HRMS(m/z):[M+Na]+calcd. for C34H30N2NaO4S,585.1819；found,585.1809；[α]D 25＝+75.3(c 0.35,CHCl3).
–7.05(m,5H),6.86(d,J＝15.2Hz,1H),4.97(d,J＝14.4Hz,1H),4.89(s,1H), 4.47(d,J＝10.8Hz,1H),4.22(d,J＝14.4Hz,1H),3.68(dd,J＝10.2,3.6Hz, 1H),2.77–2.62(m,2H),2.35(s,3H)；13C NMR(150MHz,CDCl3):δ189.1,169.1, 144.6,143.9,141.5,136.9,136.2,133.8,133.5,132.2,129.9,129.9,128.8,128.8, 128.8,128.7,128.7,128.7,128.7,128.7,128.7,127.8,127.1,127.1,125.7,125.2, 124.3,115.9,64.6,64.2,50.2,38.6,35.2,21.5；IR(neat):vmax＝2922,1670,1460, 1355,1166,733,699,665cm–1；HRMS(m/z):[M+Na]+calcd.for C34H30N2NaO4S,585.1819； found,585.1809；[α]D 25＝+6.6(c 0.11,CHCl3).
实施实例9：化合物V的制备：
氩气保护下，将Ir(dtbbpy)(ppy)2PF6(0.3mg,0.347μmol,0.005equiv.)、KHCO3(34.7 mg,0.347mmol,5.0equiv.)、2,3-丁二烯酸甲酯(14.0mg,0.140mmol,2.0equiv.)和底物I-a(30.0mg,0.069mmol,1.0equiv.)置于10mL干燥试管中，混合物用干燥脱气四氢呋喃(3mL)溶解，35℃下用5W蓝色LED灯照射15h。抽干溶剂，柱层析(石油醚：丙酮，4:1，v/v)纯化得V(33.0mg)，收率90％。
化合物V的检测数据如下：TLC(petroleum ether:EtOAc,1:3v/v):Rf＝0.60；1HNMR(400 MHz,CDCl3):δ7.43(d,J＝8.0Hz,2H),7.38(d,J＝8.0Hz,1H),7.28–7.15(m, 4H),7.13(d,J＝8.0Hz,2H),7.06(d,J＝4.4Hz,2H),6.85(d,J＝7.2Hz,2H), 5.35(d,J＝14.4Hz,1H),5.21(s,1H),5.09(s,1H),4.54(d,J＝10.0Hz,1H), 4.43(s,1H),3.75(s,3H),3.65–3.50(m,2H),3.47–3.31(m,2H),2.85(dd, J＝15.6,6.0Hz,1H),2.64(d,J＝15.6Hz,1H),2.32(s,3H)；13C NMR(100MHz,CDCl3): δ171.8,169.9,144.2,141.5,137.8,136.2,134.0,133.0,129.6,129.6,128.4,128.4, 128.4,128.3,128.3,127.3,126.9,126.9,125.2,124.0,116.4,115.9,67.2,61.0, 52.2,49.0,39.1,38.3,34.0,21.5；IR(neat):vmax＝2924,1733,1663,1353,1166, 667,579cm–1；HRMS(m/z):[M+Na]+calcd.forC30H30N2NaO5S,553.1768；found,553.1761； [α]D 25＝+149.1(c 0.8,CHCl3).
实施实例10：化合物VI的制备：
氩气保护下，将Ir(dtbbpy)(ppy)2PF6(0.3mg,0.347μmol,0.005equiv.)、KHCO3(34.7mg, 0.347mmol,5.0equiv.)、丙烯酸甲酯化合物(44.0mg,0.170mmol,2.5equiv.)和底物 I-a(30.0mg,0.069mmol,1.0equiv.)置于10mL干燥试管中，混合物用干燥脱气四氢呋喃(6mL)溶解，35℃下用5W蓝色LED灯照射15h。抽干溶剂，柱层析(石油醚：丙酮，4:1，v/v)纯化得VI(26.0mg)，收率71％。
化合物VI的检测数据如下：TLC(petroleum ether:EtOAc,1:2v/v):Rf＝0.60；1HNMR(400 MHz,CDCl3):δ7.43(d,J＝8.0Hz,1H),7.39(d,J＝8.4Hz,2H),7.25–7.16(m, 4H),7.12(d,J＝8.0Hz,2H),7.08–7.02(m,2H),6.98(d,J＝6.8Hz,2H),6.41 (s,1H),5.66(s,1H),5.00(d,J＝14.4Hz,1H),4.21–4.10(m,2H),4.02(d,J ＝14.4Hz,1H),3.84(s,3H),3.67–3.56(m,1H),2.87(dd,J＝16.0,6.8Hz,1H), 2.74(d,J＝16.0Hz,1H),2.62(d,J＝8.0Hz,2H),2.33(s,3H)；13C NMR(151MHz, CDCl3):δ168.5,166.9,144.1,141.8,136.5,136.5,134.0,132.6,129.6,129.6,129.0, 128.6,128.6,128.5,128.4,128.4,127.5,127.0,127.0,125.0,124.1,116.0,61.9, 61.6,52.3,49.4,37.9,35.9,34.8,21.5；IR(neat):2953,1655,1440,1168,732, 665,578cm–1；HRMS(m/z):[M+Na]+calcd.forC30H30N2NaO5S,553.1768；found,553.1763； [α]D 25＝+93.6(c 0.67,CHCl3).
实施实例11:化合物1的制备
化合物III-j(200mg,0.433mmol,1.0equiv.)和Pd(OH)2(200mg)溶于20mL乙酸乙酯，于氢气环境下(1atm)，室温搅拌反应。待原料完全消失后，将反应液经硅藻土过滤，浓缩滤液得无色油状粗品。经硅胶柱层析纯化(石油醚/乙酸乙酯,1:1v/v)得化合物1(172mg,白色泡沫状固体，收率86％)。
化合物1的检测数据如下：1H NMR(600MHz,CDCl3):δ7.66(d,J＝7.8Hz,1H),7.54 –7.50(m,2H),7.27(d,J＝2.4Hz,1H),7.19(d,J＝7.8Hz,2H),7.09(t,J＝ 7.5Hz,1H),7.02(d,J＝7.2Hz,1H),4.48(dd,J＝12.6,3.6Hz,1H),4.25(dd, J＝9.6,3.0Hz,1H),3.72(dt,J＝12.6,2.4Hz,1H),3.32(t,J＝8.4Hz,1H),2.74 (dd,J＝17.4,2.4Hz,1H),2.60(dd,J＝17.4,6.6Hz,1H),2.45–2.41(m,1H), 2.40–2.35(m,5H),2.35–2.31(m,1H),2.14–2.09(m,1H),1.83(dd,J＝13.2, 3.6Hz,1H),1.69(qt,J＝13.2,4.2Hz,1H),1.55–1.52(m,1H),1.46–1.35(m, 3H)；13C NMR(150MHz,CDCl3):δ209.9,168.3,144.4,141.3,134.7,133.9,129.8, 129.8,128.6,126.9,126.9,125.6,123.5,117.3,61.4,62.7,53.6,49.7,42.2,41.2, 37.1,31.9,30.9,28.7,25.9,21.6。HRMS-ESIC26H29N2O4S[M+H+]分子量计算值：465.1843；分子量实测值：465.1845。
实施实例12：化合物2a/b的制备
化合物1(40.3mg,0.091mmol,1.0equiv.)溶于4.0mL干燥甲醇中，加入硼氢化钠(10.2 mg,0.273mmol,3.0equiv.)，室温下搅拌反应。待原料完全消失后，加入饱和氯化铵溶液淬灭反应，乙酸乙酯萃取(3×5mL)，合并有机相，无水硫酸钠干燥，滤过，浓缩得无色油状粗品。经硅胶柱层析纯化(石油醚/乙酸乙酯,3:2v/v)后得化合物2a/b(35.9mg,白色粉末，收率89％)。
化合物2a/b的检测数据如下：1H NMR(600MHz,CDCl3):δ7.64(d,J＝7.8Hz,3H),7.48 (t,J＝8.4Hz,6H),7.29–7.27(m,3H),7.17–7.15(m,6H),7.13–7.08(m, 3H),7.01(t,J＝7.2Hz,3H),4.37–4.30(m,2H),4.28–4.15(m,4H),3.92(brs, 1H),3.73(brs,2H),3.57–3.50(m,1H),3.48–3.45(m,2H),3.28(td,J＝9.6, 4.8Hz,2H),3.15–3.10(m,3H),2.75(dt,J＝13.2,3.6Hz,2H),2.72–2.60(m, 5H),2.35(s,9H),2.21(t,J＝12.0Hz,2H),2.16–2.08(m,2H),2.05–2.00(m, 3H),1.85(d,J＝13.2Hz,1H),1.80–1.76(m,2H),1.73–1.66(m,1H),1.66– 1.60(m,1H),1.60–1.47(m,3H),1.40–1.28(m,3H),1.27–1.11(m,5H),0.89 (m,4H)；13C NMR(150MHz,CDCl3):δ168.9,168.2,144.4,141.1,135.4,135.1,134.9, 134.8,129.8,129.7,128.5,128.5,126.9,126.8,126.1,126.0,123.5,123.5,118.6, 118.3,73.7,68.8,65.5,65.2,63.7,60.9,59.5,53.4,49.4,48.7,47.9,45.1,42.0, 38.5,37.0,36.8,35.4,34.6,34.1,33.4,33.3,31.9,31.5,29.5,29.2,27.0,23.4, 21.6,19.2。HRMS-ESI C26H30NaN2O4S[M+Na+]分子量计算值：489.1818；分子量实测值： 489.1817。
实施实例13：化合物3:的制备
化合物2a/b(25.2mg,0.054mmol,1.0equiv.)在氩气保护下溶于4.0mL干燥四氢呋喃。 0℃下缓慢加入氢化钠(21.5mg,0.540mmol,10.0equiv.)，维持该温度搅拌30分钟后，缓慢加入二硫化碳(64μL,1.07mmol,20.0equiv.)，随后升至室温搅拌反应20分钟。随后加入碘甲烷(67μL,1.07mmol,20.0equiv.)，于35℃搅拌反应3小时。待原料完全消失后，加入饱和氯化铵溶液淬灭反应，分出有机层，水层以乙酸乙酯萃取(3×5mL)，合并有机层，无水硫酸钠干燥，滤过，浓缩。粗品不经纯化直接溶于5.0mL干燥甲苯中，氩气保护下加入 AIBN(7.2mg,0.050mmol,1.0equiv.)和三丁基锡氢(67μL,0.250mmol,5.0equiv.)，升温至80℃反应约3小时。待原料完全消失后，将反应液冷却至室温，旋干溶剂，粗品经硅胶柱层析纯化(石油醚/乙酸乙酯,3:1v/v)后得化合物3(18.1mg，白色泡沫状固体，收率74％)。化合物3的检测数据如下：1H NMR(600MHz,CDCl3):δ7.65(d,J＝7.8Hz,1H),7.48 (d,J＝7.8Hz,2H),7.28–7.26(m,1H),7.16(d,J＝8.4Hz,2H),7.11(t,J＝ 7.2Hz,1H),7.01(d,J＝7.2Hz,1H),4.28(dd,J＝13.2,4.2Hz,1H),4.18(dd, J＝9.0,5.4Hz,1H),3.47(ddd,J＝12.0,5.4,3.6Hz,1H),3.11(dt,J＝8.4,6.0 Hz,1H),2.67(d,J＝6.0Hz,2H),2.36(s,3H),2.23(dt,J＝13.2,3.0Hz,1H), 2.20–2.11(t,J＝12.3Hz,1H),1.74(d,J＝10.2Hz,3H),1.66–1.59(m,1H), 1.29–1.20(m,4H),1.18–0.99(m,2H),0.92–0.85(m,1H)；13C NMR(150MHz, CDCl3):δ168.5,144.3,141.1,135.4,135.0,129.7,128.5,126.9,126.0,123.5,118.6, 112.5,65.4,60.1,49.4,41.0,40.7,38.6,36.9,32.6,31.7,29.8,28.3,26.0,25.7, 21.6。HRMS-ESI C26H31N2O3S[M+H+]分子量计算值：451.2050；分子量实测值：451.2050。
实施实例14:化合物4的制备
化合物3(37.3mg,0.082mmol,1.0equiv.)溶于4.0mL甲醇，加入镁屑(40.5mg,1.64mmol,20.0equiv.)，室温下剧烈搅拌反应约3小时。待原料完全消失后，加饱和氯化铵溶液淬灭反应，乙酸乙酯萃取(3×5mL)，合并有机层，无水硫酸钠干燥，滤过，粗品经硅胶柱层析纯化(石油醚/乙酸乙酯,2:1v/v)得化合物4(20.4mg，白色泡沫状固体，收率83％)。
化合物4的检测数据如下：1H NMR(400MHz,CDCl3):δ7.07(d,J＝8.0Hz,2H),6.76(t,J＝7.2Hz,1H),6.65(d,J＝7.6Hz,1H),4.33(dd,J＝12.8,3.2Hz,1H),4.06 (s,NH),3.78(dd,J＝8.8,5.6Hz,1H),3.62(q,J＝8.8Hz,1H),3.38(dt,J＝10.0, 5.6Hz,1H),2.74(dd,J＝16.4,6.8Hz,1H),2.50(dd,J＝16.4,9.6Hz,1H),2.27 (t,J＝12.0Hz,1H),1.90(dd,J＝10.0,4.0Hz,1H),1.81–1.64(m,4H),1.27 (d,J＝11.2Hz,3H),1.20–1.05(m,3H),1.05–0.82(m,1H)；13C NMR(150MHz, CDCl3):δ171.2,149.3,131.9,128.1,123.8,119.6,109.9,63.8,58.5,48.7,40.4, 40.0,39.9,38.0,34.8,32.7,30.0,26.0,25.7。HRMS-ESIC19H25N2O[M+H+]分子量计算值：297.1961；分子量实测值：297.1962。
实施实例15：化合物5的制备
氩气保护下，化合物4(25.5mg,0.080mmol,1.0equiv.)溶于25mL干燥四氢呋喃，加入苯亚硒酸酐(33.7mg,0.090mmol,1.1equiv.)，40℃搅拌反应约3小时。待原料完全消失后，加入饱和碳酸氢钠溶液淬灭反应，分出有机层，水层以乙酸乙酯萃取(3×10mL)，合并有机层，无水硫酸钠干燥，滤过，粗品经硅胶柱层析纯化(石油醚/乙酸乙酯,1:1v/v)得化合物5(21.4mg，白色泡沫状固体，收率86％)。
化合物5的检测数据如下：1H NMR(400MHz,CDCl3):δ7.91(s,NH),7.47(d,J＝7.6Hz,1H),7.35(d,J＝8.0Hz,1H),7.21(t,J＝7.6Hz,1H),7.14(t,J＝7.6Hz, 1H),4.85(dd,J＝13.2,3.6Hz,1H),4.67–4.64(m,1H),3.72(d,J＝3.6Hz,2H), 2.34(t,J＝12.4Hz,1H),2.11(d,J＝11.2Hz,1H),1.79–1.68(m,4H),1.43– 1.25(m,5H),1.11–0.95(m,2H)；13C NMR(150MHz,CDCl3):δ166.9,136.6,129.8, 126.0,122.5,120.0,118.5,110.9,104.9,56.2,48.5,41.8,41.6,41.5,32.5,29.8, 29.3,26.1,25.7。HRMS-ESI C19H23N2O[M+H+]分子量计算值：295.1805；分子量实测值： 295.1802。
实施实例16：Yohimbane的制备:
氩气保护下，化合物5(15.3mg,0.052mmol,1.0equiv.)和[Rh(H)(CO)(PPh3)3](2.3mg,0.003mmol,0.05equiv.)溶于3.0mL干燥四氢呋喃，随后缓慢加入PhSiH3(19μL,0.152mmol,3.0equiv.)，室温下搅拌反应。待原料完全消失后，加入饱和氟化铵溶液淬灭反应，分出有机层，水层以乙酸乙酯萃取(3×5mL)，合并有机层，无水硫酸钠干燥，滤过，浓缩。粗品经硅胶柱层析纯化(石油醚/乙酸乙酯,1:1v/v)得(+)–yohimbane(12.7mg，黄白色泡沫状固体，收率87％)。
Yohimbane检测数据如下：1H NMR(600MHz,CDCl3):δ7.72(brs,1H),7.47(d,J＝7.8Hz,1H),7.30(d,J＝7.8Hz,1H),7.12(t,J＝7.8Hz,1H),7.08(t,J＝7.8Hz, 1H),3.29(d,J＝10.8Hz,1H),3.09(q,J＝5.4Hz,1H),3.04–2.99(m,1H),2.90 (dd,J＝10.8,3.6Hz,1H),2.72(dd,J＝15.0,4.2Hz,1H),2.61(td,J＝11.4,4.2 Hz,1H),2.13(t,J＝10.8Hz,1H),2.00(dt,J＝12.0,3.6Hz,1H),1.76(d,J＝ 4.8Hz,2H),1.71(d,J＝8.4Hz,1H),1.62(s,1H),1.50–1.43(m,1H),1.38(q, J＝12.0Hz,1H),1.34–1.28(m,2H),1.28–1.16(m,1H),1.13–1.07(m,1H), 1.09–0.98(m,1H)；13C NMR(150MHz,CDCl3):δ135.9,135.1,127.5,121.2,119.3, 118.1,110.7,108.1,62.1,60.2,53.2,42.0,42.0,37.0,32.9,30.4,26.4,26.0,21.8。 HRMS-ESI C19H25N2[M+H+]分子量计算值：281.2012；分子量实测值：281.2010。

Claims (13)

1.具有式I结构的化合物：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；
R选自(1)：其中n为0-3之间的整数；R3，R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构；
或者R选自(2)：其中n为0-3之间的整数；R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构；
或者R为(3)：苄基或对甲氧基苄基；
或者R为(4)：其中R7选自吸电子基团或亚甲基连接的离去基团。
2.具有式II或式II’结构的化合物：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；
n为0-3之间的整数；R3，R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构。
3.具有式III结构的化合物：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；
R6和R7选自各种吸电子基团或亚甲基连接的离去基团。
4.具有式IV，式V或式VI结构的化合物：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；R为苄基或对甲氧基苄基；R8为吸电子基团。
5.一种合成权利要求1所述式I化合物的方法，其特征在于，包括如下步骤：
在R-NH2的存在下通过缩合生成将硝基还原为氨基，可选的，将氨基上的一个氢原子用R2基团进行取代；
R选自(1)：其中n为0-3之间的整数；R3，R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构；
或者R选自(2)：其中n为0-3之间的整数；R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构；
或者R为(3)：苄基或对甲氧基苄基；
或者R为(4)：其中R7选自吸电子基团或亚甲基连接的离去基团。
6.一种制备如权利要求2所述式II化合物的方法，其特征在于，包括式I化合物在可见光光照的条件下发生自由基串联反应：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；
R选自其中n为0-3之间的整数；R3，R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构。
7.一种制备如权利要求2所述式II’化合物的方法，其特征在于，包括式I化合物在可见光光照的条件下发生自由基串联反应：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；
R选自其中n为0-3之间的整数；R4，R5分别选自氢，各种吸电子基团或供电子基团；或者R4，R5形成5-7元饱和或者不饱和环状结构。
8.一种制备如权利要求3所述式III化合物的方法，其特征在于，包括式I化合物与化合物在可见光光照的条件下反应生成式III所示化合物：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；R6选自吸电子基团或亚甲基连接的离去基团；R为其中R7选自吸电子基团或亚甲基连接的离去基团。
9.一种制备如权利要求4所述式IV化合物的方法，其特征在于，包括式I化合物与在可见光光照的条件下发生自由基串联反应：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；R选自苄基或对甲氧基苄基；R8为吸电子基团。
10.一种制备如权利要求4所述式V及式VI化合物的方法，其特征在于，包括式I化合物在光照下分别与发生自由基串联反应：
其中R1为在苯环上的单取代或多取代，R1选自H，C1-C6的烷基或C1-C6的烷氧基；R2选自对甲苯磺酰基或邻硝基苯磺酰基；R选自苄基或对甲氧基苄基。
11.根据权利要求5-9所述制备方法，其特征在于，光源为可见光，优选为5W蓝色LED灯；光敏剂可使用Ir(dtbbpy)(ppy)2PF6，Ru(bby)3Cl2·6H2O，Ir(dF(CF3)ppy)2(bpy)PF6和Ru(bby)3Cl2等，优选为Ir(dtbbpy)(ppy)2PF6；碱可使用各种无机碱及有机碱如碳酸钾、碳酸铯、碳酸氢钾、三乙胺、二异丙基乙基胺等，优选为碳酸氢钾；温度可为0℃到50℃，优选为35℃；溶剂可使用各类有机溶剂如甲苯、1,2-二氯乙烷、二氧六环、N,N-二甲基甲酰胺、四氢呋喃、乙腈、二氯甲烷及相应溶剂与水的混合溶剂，优选为四氢呋喃。
12.式II-VI所述化合物在天然产物全合成中的应用。
13.根据权利要求12所述的应用，其特征在于，III在(+)-Yohimbane全合成中的应用。
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CN113698402A (zh) * 2021-10-28 2021-11-26 华南理工大学 具有抗炎活性的天然生物碱Arbornamine的合成方法及应用
CN115043770A (zh) * 2022-07-21 2022-09-13 南京大学 一种吲哚/氮杂吲哚类化合物的光诱导合成方法
CN115043770B (zh) * 2022-07-21 2023-09-08 南京大学 一种吲哚/氮杂吲哚类化合物的光诱导合成方法

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