The first enantioselective synthesis of (−)-conolutinine was achieved in 10 steps. The synthesis featured a catalytic asymmetric bromocyclization of tryptamine to forge the tricycle intermediate. Hydration of an alkene catalyzed by Co(acac)₂ was also employed as a key step to diastereoselectively introduce the tertiary alcohol moiety. The absolute configuration of (−)-conolutinine was established to be (2S,5aS,8aS,13aR) based on this asymmetric total synthesis.

 

 

Total Synthesis of (−)-Conolutinine

Xiangyang Feng^†‡, Guangde Jiang^‡, Zilei Xia^‡, Jiadong Hu^†‡, Xiaolong Wan^§, Jin-Ming Gao^†, Yisheng Lai^*‡, and Weiqing Xie^*†§

^† Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, 22 Xinong Road, Yangling 712100, Shaanxi, China

^‡ State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, Center of Drug Discovery, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China

^§ State Key Laboratory of Bioorganic & Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China

Org. Lett., Article ASAP

DOI: 10.1021/acs.orglett.5b02046

http://pubs.acs.org/doi/abs/10.1021/acs.orglett.5b02046

 http://pubs.acs.org/doi/suppl/10.1021/acs.orglett.5b02046/suppl_file/ol5b02046_si_001.pdf

*E-mail: yslai@cpu.edu.cn., *E-mail: xiewq@nwafu.edu.cn.

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