Total Synthesis Of Hamigerans And Gukulenins

Part I: total synthesis of hamigerans.The first total synthesis of 10 members of hamigerans has been accomplished by a unified and convergent route.The all-carbon quaternary stereocenter was constructed by semipinacol rearrangement,and then the sequential Suzuki-Miyaura cross coupling and Mc Murry coupling with the aromatic ring could give the 5-6-6 tricarbocyclic skeleton efficiently.Exploring the selective hydrogenation of tetrasubstituted olefins could efficiently construct the continuous chiral centers(C5,C6),then we completed the formal synthesis of hamigeran B through the known oxidation(17%,13 steps).The direct expansion of the B ring has not obtained the desired results,therefore we revised our strategy for generating the 5-7-6 tricarbocyclic skeleton.After a sequence of oxidative cleavage,homologation and intramolecular aldol reaction,we have achieved the first total synthesis of hamigeran G with 20 steps,in 8.4% yield.Inspired by the biosynthetic hypothesis,reacting hamigeran G with appropriate amino acids could complete the synthesis of hamigergan D,N-Q and their 18-epimers(1.2%-2.3%,21 steps),and hamigeran G could be transformed to hamigeran L by oxidative cleavage(2.4%,24 steps).In this part,we have accomplished the first diversity total synthesis of hamigerans.Part II: synthesis of gukulenins.The tropolones of gukulenins was designed to be constructed by the cyclopropanation followed by ring opening strategy,which could be used in the synthesis of gukulenins monomers and dimers.The 5-6-6 tricarbocyclic skeleton was completed in 8 steps,29% yield based on the Suzuki-Miyaura cross coupling,Mc Murry coupling and the selective hydrogenation of tetrasubstituted olefins,which has been developed in part I.After investigation of different methylation methods,the methyl three 5-6-6-3 tetracarbocyclic compounds were obtained by reacting with different cyclopropanation reagents.Then we explored the conditions of cyclopropane opening extensively,but we have not obtained the desired results,and the relevant work is still in progress.In part II,the currrent work can provide a foundation for the total synthesis of gukulenins.