Design,Syntheses And Bioevaluation Of Natural Alkaloids And Amino Acids

Fascaplysin was the first natural bis-indole alkaloid isolated in 1988 from the marine sponge Fascaplysinopsis sp..Fascaplysin exhibits a broad range of bioactivities.However,only a few Fascaplysin derivatives exist,so we have designed and synthesized several new derivatives with functional group structures and conducted pharmacological studies on them.Seven new derivatives were obtained.Two new Fascaplysin derivatives were generated by the cyclization reaction.We then performed pharmacological studies on the inhibitory effect of these derivatives on glioma at the cellular level.According to the results,these derivatives have a good inhibitory effect on the growth of glioma.We have provided several novel derivatives for Fascaplysin as a potential anticancer active agent.γ-Butyric acid is a non-protein amino acid or GABA for short.In mammals’brains,high levels of GABA and L-glutamate are used as inhibitory neurotransmitters and excitatory neurotransmitters,respectively.When levels of GABA in the brain drop,it could be a host of neurodegenerative or psychiatric disorders,such as schizophrenia,depression,Alzheimer’s disease,and epilepsy.To increase the concentration of GABA,the effect can be achieved by inhibiting GABA transaminase(GABA-AT).Studies have shown that carbocyclic nucleosides containing cyclopentene structure can inhibit GABA-AT.These carbocyclic nucleoside compounds can be obtained by the hydrolysis of amido-norbornene derivatives with functionalization in alkene’s structure.Our group has realized the research on the preparation of GABA-AT inhibitors through the synthesis method of three-step reaction.The method uses the super alkali system(~nBu Li+KO~tBu)to achieve a high yield of amido-norbornene derivatives with multi-functional group.However,due to its small steric hindrance,the ~nBu Li organic base used in this method is easy to undergo additional reactions with substrates in the reaction process.Therefore,we replace the super base(~nBu Li+KO~tBu)with LDA(Lithium diisopropyl amide),having a higher steric resistance,and then realized the direct functionalization of amido-norbornene in the alkene’s structure.This method has mild conditions and a high reaction yield.