文献类型：期刊文献

英文题名：Total Synthesis and Stereochemical Assignment of Delavatine A: Rh-Catalyzed Asymmetric Hydrogenation of Indene-Type Tetrasubstituted Olefins and Kinetic Resolution through Pd Catalyzed Triflamide-Directed C-H Olefination

作者：Zhang, Zhongyin[1,2,3];Wang, Jinxin[2,3];Li, Jian[3];Yang, Fan[1];Liu, Guodu[3];Tang, Wenjun[3];He, Weiwei[1];Fu, Jian-Jun[1];Shen, Yun-Heng[2];Li, Ang[3];Zhang, Wei-Dong[1,2]

机构：[1]East China Univ Sci & Technol, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Second Mil Med Univ, Sch Pharm, Dept Phytochem, 325 Guohe Rd, Shanghai 200433, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Organ Chem, Collaborat Innovat Ctr Chem Life Sci, State Key Lab Bioorgan & Nat Prod Chem, 345 Lingling Rd, Shanghai 200032, Peoples R China

年份：2017

卷号：139

期号：15

起止页码：5558

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20171703603556);WOS:【SCI-EXPANDED(收录号:WOS:000399966000038)，CCR-EXPANDED(收录号:WOS:000399966000038)】；

基金：We thank Prof. Shou-Fei Zhu and Dr. David Edmonds for helpful discussions and Xiaoli Bao and Lingling Li from the Instrumental Analysis Center of Shanghai Jiao Tong University for X-ray crystallographic analysis. Financial support was provided by Ministry of Science & Technology (2013CB-836900), Chang Jiang Scholar Program, National Natural Science Foundation of China (21525209, 21290180, 21621002, 21572064, 81502956, 81230090, 81520108030, 81573318, and 81373301), Chinese Academy of Sciences (Strategic Priority Research Program XDB20020000), Shanghai Science and Technology Commission (15JC1400400, 17XD1404600, and 15PJ1401300), K. C. Wong Education Foundation, the Fundamental Research Funds for the Central Universities, and State Key Laboratory of Bioorganic and Natural Products Chemistry.

语种：英文

外文关键词：Synthesis (chemical) - Cell culture - Kinetics - Olefins - Reaction intermediates - Stereochemistry - Palladium compounds - Polycyclic aromatic hydrocarbons - Catalysis - Hydrogenation - Sulfur compounds

摘要：Delavatine A (1) is a structurally unusual isoquinoline alkaloid isolated from Incarvillea delavayi. The first and gram-scale total synthesis of 1 was accomplished in 13 steps (the longest linear sequence) from commercially available starting materials. We exploited an isoquinoline construction strategy and developed two reactions, namely Rhcatalyzed asymmetric hydrogenation of indene-type tetrasubstituted olefins and kinetic resolution of beta-alkyl phenylethylamine derivatives through Pd-catalyzed triflamide-directed C-H olefination. The substrate scope of the first reaction covered unfunctionalized olefins and those containing polar functionalities such as sulfonamides. The kinetic resolution provided a collection of enantioenriched indane- and tetralin-based triflamides, including those bearing quaternary chiral centers. The selectivity factor (s) exceeded 100 for a number of substrates. These reactions enabled two different yet related approaches to a key intermediate 28 in excellent enantiopurity. In the synthesis, the triflamide served as not only an effective directing group for C-H bond activation but also a versatile functional group for further elaborations. The relative and absolute configurations of delavatine A were unambiguously assigned by the syntheses of the natural product and its three stereoisomers. Their cytotoxicity against a series of cancer cell lines was evaluated.