1、有机化学有机化学 Chinese Journal of Organic Chemistry ARTICLE *Corresponding author.E-mail: Received August 13,2022;revised September 2,2022;published online October 10,2022.Project supported by the National Natural Science Foundation of China(No.21971104),the Key Research Projects in Colleges and Universit
2、ies of Education Department of Guangdong Province(No.2021ZDZX2035),the Shenzhen Bay Laboratory(No.SZBL2019062801006),the Shenzhen Nobel Prize Scientists Laboratory Project(No.C17783101),the Guangdong Innovative Program(No.2019BT02Y335),the Innovative Team of Universities in Guangdong Province(No.202
3、0KCXTD016),the Guangdong Provincial Key Laboratory of Catalysis(No.2020B121201002)and the Shenzhen Science and Technology Innovation Committee(No.ZDSYS20190902093215877).国家自然科学基金(No.21971104)、广东省教育厅高校重点科研项目(No.2021ZDZX2035)、深圳湾实验室(No.SZBL2019062801006)、深圳市诺贝尔奖科学家实验室(No.C17783101)、广东省本土创新团队项目(No.2019
4、BT02Y335)、广东省高校创新团队(No.2020KCXTD016)、广东省催化化学重点实验室(No.2020B121201002)、深圳市科技创新委员会(No.ZDSYS20190902093215877)资助项目.Chin.J.Org.Chem.2023,43,171177 2023 Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences http:/sioc- DOI:10.6023/cjoc202208014 研究论文研究论文 Daphnezomines A 和 B 的四环核心骨架合成 胡晶平a,b 陈
5、文清b 蒋宇旸b 徐 晶*,b,c(a哈尔滨工业大学化工与化学学院 哈尔滨 150001)(b南方科技大学化学系与格拉布斯研究院 广东省催化化学重点实验室 深圳市小分子药物发现与合成重点实验室 广东深圳 518055)(c深圳湾实验室 广东深圳 518132)摘要摘要 在虎皮楠生物碱家族中,daphnezomine A 型生物碱仅包含三位成员:daphnezomine A(1),daphnezomine B(2)以及dapholdhamine B.这些生物碱含有独特的氮杂金刚烷骨架,9 个连续的手性立体中心,因此呈现出巨大的合成挑战性.报道了分子 1 和 2 的四环核心骨架的合成.关键步骤包括
6、一个黄氏酰胺活化增环反应和一个 Hutchins-Kabalka 还原重排反应.关键词关键词 全合成;虎皮楠生物碱;daphnezomine A;daphnezomine B;氮杂金刚烷;黄氏酰胺活化增环反应;Hutchins-Kabalka 还原重排 Synthesis of Tetracyclic Core Structure of Daphnezomines A and B Hu,Jingpinga,b Chen,Wenqingb Jiang,Yuyangb Xu,Jing*,b,c(a School of Chemistry and Chemical Engineering,Harbi
7、n Institute of Technology,Harbin 150001)(b Department of Chemistry and Shenzhen Grubbs Institute Guangdong Provincial Key Laboratory of Catalysis Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis,Southern University of Science and Technology,Shenzhen,Guangdong 518055)(c Shenzhen
8、 Bay Laboratory,Shenzhen,Guangdong 518132)Abstract Among the tiniest Daphniphyllum alkaloid subfamilies,daphnezomine A-type alkaloids consist of only three known members,namely daphnezomine A(1),daphnezomine B(2)and dapholdhamine B.These alkaloids contain a unique aza-adamantane core along with nine
9、 contiguous stereogenic centers,thus presenting remarkable synthetic challenges.The synthesis of tetracyclic core structure of 1 and 2 was reported.The key steps in our approach include a Huangs amide-activa tion-annulation and a Hutchins-Kabalka reductive rearrangement.Keywords total synthesis;Daph
10、niphyllum alkaloids;daphnezomine A;daphnezomine B;aza-adamantane;Huangs am-ide-activation-annulation;Hutchins-Kabalka reductive rearrangement 1 Introduction Since the isolation of daphnimacrine in 1909,more than 350 Daphniphyllum alkaloids have been isolated.They consist of a large family of structu
11、rally intriguing natural products with a wide range of bioactivity.1 Owing to their promising pharmacological potential and complex archi-tectures,Daphniphyllum alkaloids have attracted extensive activities from organic synthesis community over the past four decades.2 Since Heathcocks seminal synthe
12、ses,3 continuous efforts have resulted in elegant total syntheses by the groups of Carreira,4 Li,5 Smith,6 Fukuyama/Yokoshima,7 Dixon,8 Zhai,9 Qiu,10 Gao,11 Sarpong,12 Li13 and Lu14.Moreover,Hanessian and his co-workers 有机化学 研究论文 172 http:/sioc- Shanghai Institute of Organic Chemistry,Chinese Academ
13、y of Sciences Chin.J.Org.Chem.2023,43,171177 have reported the total synthesis of a putative natural Daphniphyllum alkaloid.11,15 Meanwhile,our group has also accomplished enantioselective total syntheses of calyciphylline A-type alkaloid himalensine A,daphne-zomine A-type alkaloid dapholdhamine B,b
14、ukitting-gine-type alkaloid caldaphnidine O and yuzurimine-type alkaloid caldaphnidine J.2d,16 2 Results and discussion Amongst the tiniest Daphniphyllum alkaloid subfamilies,daphnezomine A-type alkaloids consist of only three known members,namely daphnezomine A(1),17 daphnezomine B(2)17 and daphold
15、hamine B(3)18(Figure 1).These alka-loids contain a unique aza-adamantane core along with nine contiguous stereocenters,thus signifying remarkable syn-thetic challenges.Fascinated by their complex caged stru-ctures,a program aiming to prepare these molecules in an efficient manner was initiated.Recen
16、tly,our group has accomplished the first total synthesis of 3.16b Soon after our report,Li and his co-workers reported efficient syntheses of 1 and 2.13 Herein,we would like to introduce our efforts toward the synthesis of 1 and 2,which successfully fabri-cated the aza-tetracyclic core structure.The key transfor-mations in our approach include Huangs amide-activation-annulation and Hutchins-Kabalka reductive rearrangement.Figure 1 Daphnezomine A-type alkaloids Despite our success in the synthesi