Abstract:

Humantenine-type compounds are a group of Gelsemium alkaloids isolated from Gelsemium elegans Benth that possess complex structures and remarkable activities. In this work, the synthetic approaches of them were investigated. The key structure of Gelsemium alkaloids humantenine(13) was efficiently constructed through a region- and stereoselectivity addition of compound 11 to compound 10. A multi-step, one pot eno-loxonium cyclization cascade was used in a highly efficient way to construct, simultaneously, the tetrahydropyran ring, oxepane ring, C3 chiral carbon and C7 chiral quaternary carbon of humantenine(2). Based the above created methodology, the key skeleton(6) of oxindole alkaloid humantenine(2), humantenine N₄-oxide(3), gelseganines A(4)and gelseganines B(5) was asymmetric synthesized in 16 steps with a total yield of 1.5%. The structures of the compounds were confirmed by IR, ¹H NMR, ¹³C NMR and high resolution mass spectrometer(HRMS). Especially, we successfully synthesized hmantenine-type skeleton which indicates this method has a widely range of applications.

Key words: Humantenine, Asymmetric synthesis, Enol-oxonium cyclization, Oxindole alkaloid