Studies On The Total Synthesis Of Lophotoxin

Lophotoxin is a unique furanocembrane diterpene isolated from Lophogorgia.Much attention has been attracted in recent years due to its complex structure and biological activity.This thesis aims at the total synthesis of Lophotoxin and a synthetic strategy has been proposed for the total synthesis of Lophotoxin(showed in figure).Highlights of the approach include the fourteen-membered macrocyclic precursor which can been synthesised from substituted furan via Diels-Alder reaction,intramolecular ketene [2+2] cycloaddition and ene reaction substuently.The key step is the fourteen-membered macrocyclic ring of the Lophotoxin constructed through the retro-Diels-Alder reaction.Perillene is the key starting material for our synthesis,to achieve our goal,the efficient synthesis of Perillene is the prerequisite.In this thesis,the coupling reaction of Grignard reagent of 3-chloromethylene furan with carbonates for the synthesis of Perillene has been developed,the yield up to 80.4%.In addition,a series of analogues of Perillene include Dendrolasin and Ambliofuran have been synthesised by using this method.The results lay the foundation for the total synthesis of Lophotoxin.