Biomimetic Synthesis Of Several Natural Dimeric Securinega-type Alkaloids

Objective：Natural securinine alkaloid, which belongs to indole alkaloid, is a kind of alkaloidwith special chemical skeleton. Its main types are divided into securinine-type andnorsecurine-type alkaloid. Most of securinine alkaloid could easily lead to the formation ofdimers, trimers as well as polymers, and show good pharmacological activities. In this thesis,we mainly explore the mechanism of biosynthetic pathways of these dimeric securinine-typealkaloids, and use chemical methods to simulate the biosynthetic pathway to synthesize thesedimers, even trimers.Method:(1)[2+2] cycloaddition: Based on the structure analysis of highly axisymmetricsecurinine alkaloid dimers, it could be explained through the chemical mechanism of [2+2]cycloaddition. So we treated securinine-and norsecurinine-type alkaloids under ultravioletlights to obtain the dimers.(2) Baylis-Hillman reaction: Other kinds of dimers and trimers with specialcombinational ways were analyzed and could be explained via Baylis-Hillman reaction.Different catalyst (including self-catalyzed) and conditions were also utilized to get this typeof dimers and trimers.(3)[2+3] cycloaddition: According to oxidation rearrangement of previous reports, the sameway was also used for securinine dimer by oxidation rearrangement and dipole [2+3]cycloaddition with another molecule of securinine to get the oxidation rearrangement dimers.Result:(1) In this thesis, a highly regio-and stereoselectivitive securinine alkaloid dimer wassynthesized which is exactly the same as the one separated by professor Ye Wencai group.Different kinds of securinine with similar structure were also used to go through [2+2]cycloaddtion reaction and achieve the same results as that of securinine. In subsequent work,the [2+2] cycloaddtion was inadvertently found that it could be carried out under normal lightcondition. At the same time, according to the high regio-and stereoselectivity of alkaloid and its low yield, different reaction time, concentration and solvent polarity and energycalculation were further discussed.(2) It was discovered that two or three molecules of norsecurinine could combine with eachother and become two main configurational trimers by Baylis-Hillman reaction. Nevertheless,as for securinine, it does not make the corresponding product through Baylis-Hillman reaction.Changing different conditions and catalysts still cannot achieve the effect.(3) In this thesis,8dimeric securinega-type alkaloids were obtained. The structures of thecompounds were characterized by ESI-MS, HRMS (ESI),1H NMR,13C NMR, DEPT-135,1H-1H COSY, HSQC, HMBC, NOESY analysis.