Synthesis Of Marine Natural Products Hymenialdisine Derivatives

The Alzheimer's disease, associated with the overexpression of kinase GSK-3βand CDK5, rank the fourth disease that causes most elder death among cancer, hypertension, diabetes and Alzheimer. The marine natural product hymenialdisine exhibits strong inhibition against the Alzheimer's disease related kinase GSK-3βand CDK5. Meanwhile, it also shows strong inhibition activities against the other members of the CDK family as well as many other kinases such as Erk1, Erk2, CK1, MEK etc. Structral modification of bioactive natural products has always been the most effective way in seaching for new drug candidates.In this thesis, The structrual modification is focused on theα-position of the pyrrole ring of hymenialdisine. the synthesis of 2-phenyl substituted and 2-benzyl substituted hymenialdisine derivatives by 7-step and 9-step reactions are reported. The new compounds are stable and with good lipophilicity, which will be used for activity screening.