Study Towards The Total Synthesis Of Salimabromide

Marine halogenated natural product is a series of organic molecular that contains novel structure and extensive biological activity.Our group has a long-term commitment to the total synthesis and structure modification of marine halogenated natural product.Previously we have achieved the total synthesis of Aplydactone and asymmetric total synthesis of(+)-Majusculoic acid.In this thesis,we study the asymmetric total synthesis towards Salimabromide,an activited marine halogenated natural product with original structure.As a new kind of secondary metabolites,Salimabromide was isolated from an obligatory marine myxobacterium named salina that cultivated from a mud specimen originated from the coast of the island Prerow(Germany)in 2013 by Prof.Konig and coworkers.Salimabromide contains an unprecedented 6/6/7/5 tetracyclic ring system that never been discovered before.It contains a dibrominated benzene ring,a all-substituted cyclohexane,a five-me mbered lactone residue,and an ?,?-unsaturated seven-membered ketene ring.Besides,it comprises four contiguous stereogenic center,and two sterically highly congested quaternary carbons.All these characteristic structure indicates the incredible challenge towards the total synthesis of Salimabromide.In consideration of the unique structure of Salimabromide,we designed a efficient synthetic strategy in synthetic study towards Salimabromide.Starting from benzyl 2-diazopropionate,the core seven-membered ring was prepared from rodium-catalyzed enantioselectivity intramolecular Buchner reaction with the addition of chiral phosphorus ligands.Introducing the benzene moity by conformation controlled asymmetric 1,4-addition,followed by lactonization and Friedel-Crafts alkylation,we were expected to reach the 6/6/7/5 ring system.Finally,after dibromination with the benzene ring,we could achieved the asymmetric total synthesis of Salimabromide hopefully.We have produced the highly functional five-seven membered ring at present.