Studies Towards Total Synthesis Of Rhodomollins A And B

The dissertation describes the total synthesis studies of rhodomollin A and rhodomollin B.It is composed of two chapters as follow:Chapter 1.Research Progress of Natural Products of Grayanane DiterpenoidsIn this chapter,the application studies of rhododendrons and the classification,activity and synthesis of grayanane diterpenids were briefly reviewed.Chapter 2.Synthetic Studies of Rhodomollins A and BThis chapter mainly introduces the isolation and synthesis of rhodomollins A and B.rhodomollins A and B are novel diterpenoids which were discovered by Yu and coworkers in 2016 from the fruits of R.molle.It was different from the skeleton structure of natural products of conventional grayanoids diterpenoids,which possess a5/5/6/6/6 five-ring systerm,in which there was an all-carbon[2.2.2]core and an oxa-[3.2.1]core skeleton then fused each other.In addition,the molecule has 10 stereogenic centers,including 8 contiguous stereogenic centers and 4 quaternary carbon centers.According to the unique structural characteristics of rhodomollins A and B,a convergent synthesis strategy was designed.The first generation of synthesis route:we constructed the[2.2.2]core structure by intramolecular Diels-Alder reaction,and assumed that the[3+2]cycloaddition reaction was the key step to construct the seven-membered ring.Due to the influence of steric hindrant effect,the[3+2]cycloaddition reaction catalyzed by Rh didn’t realize.Second generation synthesis route:we connected the two fragments between C1 and C10 through an intermolecular nucleophilic addition reaction.Due to the low yield and poor stereoselectivity of this reaction,subsequent synthesis was very difficult.The third generation synthesis route:we connected the two fragments between C5 and C6 through Sonogashira cross-coupling,and envisioned that cyclization of seven-membered ring through intramolecular Heck reaction,which didn’t realize due to the steric hindrant effect.The fourth generation synthesis route:we connected the two fragments between C1 and C10by Stille cross-coupling reaction,and attempt to construct the seven-membered ring by step cyclization strategy.Due to the long route and low yield,the subsequent synthesis was very difficult,and the connection between C5 and C6 is unsuccessful.The fifth generation synthesis route:C6 was introduced into the C5 position of the A ring fragment to overcome the steric hindrant effect,the two fragments were connected by Stille cross-coupling between C1 and C10,the seven-membered ring was constructed by intramolecular nuclephilic addition reaction,and the oxa-[3.2.1]core structure was constructed by Mukaiyama hydration for oxidation and S_N2 substitute reaction.The final oxidation state was adjusted by the tandem Payne/Meinwald rearrangement reaction.Finally,the first asymmetric total synthesis of rhodomollins A and B was achieved in 28 longest linear steps.