Total Synthesis Of Zoanthamine Family Natural Products

This dissertation mainly focuses on the total synthesis of zoanthamine alkaloids.Zoanthamine alkaloids are a family of marine natural products with high structural complexity and diverse biological activity.Most of them harbor the common highly functionalized and stereochemically core structure and several challenging all-carbon quaternary stereocenters.Here,we reported a unique and efficient strategy for the total syntheses of norzoanthamine and the core structure of zoanthenol.The Ueno–Stork radical cyclization was utilized to install the contiguous allcarbon quaternary centers at C-9 and C-22 positions;the Fe-catalyzed HAT radical reaction and the Co-catalyzed HAT radical reaction were applied to forge A-B-C ring with newly formed all-carbon quaternary center at C-12;the Mn-catalyzed HAT radical reaction was chosen to stereospecifically reduce the challenging tetra-substituted olefin(C13=C18)to contruct the trans-arrayed A-B ring.These approaches allow for the rapid access to the core structure of norzoanthamine.Through the further oxidation state adjustion and fragment-coupling,the biomimic precursor of the norzoanthamine was efficiently obtained.Afterwards,we realized the synsthesis of norzoanthamine with one-pot bio-inspired cyclization.Eventually,from the known compound,the total synthesis of norzoanthamine was accomplished in 33 longest linear steps.The formal synthesis of zoanthenol was also realized with norzoanthamine as the starting material.Furthermore,under the direction of our above described apporoaches for norzoanthamine,the highly functionalized skeleton of zoanthenol was efficiently constructed through Co-catalyzed HAT reaction.Our synthetic research further verified the proposed biogenetic pathway.At the same time,this reasearch provided a new method for the syntheses of other zoanthamine alkaloids and their related derivatives.