Asymmetric Divergent Total Syntheses Of Illicium Anislactone-type Sesquiterpenes

With structures varying from citronellal,artemisinin to taxol and natural rubber,terpenes are a wide variety of natural products with complex structures and a broad range of functions.More than thousands of terpenes have been isolated so far,and used in the form of flavors,medicines and materials.Sesquiterpenes are a subclass of terpenoids which usually contains 15 carbon atoms(three isoprene units)and exhibit wide biological activities,such as anti-tumor,anti-malaria,antibacterial,anti-inflammatory and analgesic effects.Illicium plants are mainly distributed in North America and vast areas from India to eastern Asia,including nearly 40 species.Many unique neurotrophic sesquiterpenes have been discovered in this genus of plants.Our research group has been committed to the total synthesis and structural modification of Illicium sesquiterpenes for a long time,aiming to find leading compounds with good biological profiles.In this dessertation,the studies towards asymmetric divergent syntheses of anislactone-type sesquiterpenes are elaborated.Anislactone-type sesquiterpenes are a nature product family with polycyclic ring system and diverse oxidation patterns.Usually,they contain a 5/5 fused carbon ring framework which is fused with two y-lactones,and five contiguous quaternary stereocenters,in particular,a highly congested five-membered ring(B ring)bearing five stereocenters.Some members,such as Merrilactone A,exhibit good neurotrophic properties.Recent studies showed that some of them have inhibitory activity against hepatitis B virus.The potential of the nature product family is still worth exploring.In the foray of total synthesis,beginning with cheap feedstock,(+)-Pulegone a pivotal tetracyclic ring system was constructed through a series of cylization transformations,including an epoxide opening/esterification cascade reaction,a palladium catalytic 1,6-enyne cyclization hydroboration-oxidation reaction and a radical cyclization reaction.And all the chiral centers of natural products were constructed with high selectivity during this process.In the final stage of the synthesis,we achieved a selective dehydrogenation/desaturation reaction which secured divergent total syntheses of four natural products including Merrilactone A.Overall,we provided an entry to the anislatone sesquiterpenes with high atom and redox economies.