Secologanin Based One-step Stereoselective Synthesis And Transformation Of Non-natural Alkaloids & "One-pot" Construction Of Indolizines And Dihydroindolizines

Alkaloids,such as terpenoid indole alkaloids and isoquinoline alkaloids,equip pivotal pharmaceutical activities and are widespread in nature.Both of these alkaloids share the same precursor,namely socologanin.Its value in biochemistry is beyond a critical precursor for alkaloid synthesis.Given rich in reactive functional groups and chiral centers,this raw material has the capability for synthesizing poly-cyclic diversified optical active compounds with intricate structures,which provides the foundation for creating novel chemical compounds with bioactivities.The second part of this thesis focuses on characteristics of socologanin's reactive functional groups.A total of twenty-one non-natural alkaloids with stereoselectivity belonging to five categories were constructed by one-step method through reactions between socologanin and dual-electronegative compounds,like phenylenediamines,ethylenediamine,hydroxylamine,ethylalcohol and prolinol.These non-natural alkaloids,including benzimidazole alkaloids,[5,6,6]-imidazolidine alkaloids,[5,5,6]-isoxazolidine alkaloids,[5,6,6]-oxazolidine alkaloids and hexahydropyrrolo-oxazole alkaloids,have chiral selective structure and many reactive sites,enabling further transformation.More interestingly,we got one Camptothecin-like and five-ring fused compound among these synthetic products.The more stable and rigid structure has been synthesised by structural modification.With the future activity screening and structural modification,we expect to get derivatives with good biological activity.In the third part of the thesis,we developed the methodologies to afford several heterocyclic compounds.Herein,we discovered a facile approach and "one-pot"multicomponent way to provide dihydroindolizine and indolizine derivatives.In summary,we have developed a new general and practical synthetic protocol for the efficient assembly of 17 polysubstituted dihydroindolizines and 17 indolizines from pyrrole-2-carboxaldehyde;2-bromo-l-phenylethanone and 2-nitrovinyl benzene,which would provide an attractive strategy for the synthesis of indolizine drug intermediate derivatives.