Studies On The Asymmetric Synthesis Of Herbarumin Ⅲ, Tuckolide, Cuparene And Flavans

This thesis focused on the application of sulfone and chiral sulfoxide in the synthesis of bioactive natural products based on Julia coupling reaction as key steps. A new scheme was found for the synthesis of Herbarumin III, a 10-membered lactone compound and it diastereomer 55. The synthesis of Tuckolide and Cuparene were attempted. Some efforts were done with the asymmetric cyclization reaction induced by chiral sulfoxide to synthesize flavans. During this term, some extra results were investigated and an efficient method was found for selective removal of phenolic TBDMS protecting group with simple organic nitrogen base in aqueous DMSO in mild condition. This thesis was described in five chapters as following.Chapter I Review on the isolation, activities and synthesis of natural products with 10-membered lactone ring skeleton10-membered lactone ring compounds exist widely and play an important role. Their obvious activities aroused wide interest and a lot of research was published on their isolation, activities and synthesis. There are more than 70 natural compounds isolated, which can inhibit the synthesis of cholesterol in liver, anti-KB cell, anti-bacterial and so on. There are a lot of methods reported on their synthesis, including the method based on intramolecular esterifications, the reaction based on ring-amplied reactions, oxidative fragmentations, or by constructing C-C or C=C bonds.Chapter II Total synthesis of 10-membered lactone ring natural product, Herbarumin III and synthesis research of TuckolideHerbarumin III is a phytotoxin and Tuckolide is a 10-membered lactonized compound with a special activity on inhibiting the form of cholesterol. Herbarumin III was synthesis from n-butanal through asymmetric allylation, sharpless dihydroxylation, Julia coupling-olefination, Yamaguchi lactonization and so on in 2.3% total yield, along with its diastereoisomer 55. Total synthesis of Tuckolide was tried from acetaldehyde through the similar procedure and key intermediate sulfone160 formed smoothly.Chapter III Research on the asymmetric synthesis of flavansChiral sulfoxide was used to induce the asymmetric cyclization of 1, 3-diaryl-1-propanol to form flavans. When the reaction proceeded with Lewis acid, it resulted in a pair of diastereoisomers in 1:1 ratio. Diastereoisomerization crystallization of this pair of products in various bases yielded in about 20%de. These results indicated that the cyclization maybe has a S_N1 process and sulfoxide hasn't attended the process. But bases can pull sulfoxide into the process of cyclization. This will serve the further research on synthesis of flavans.Chapter IV Research on asymmetric synthesis of aromatic terpenoids CupareneThree schemes were tried for the asymmetric synthesis of Cuparene based on Julia coupling-olefination. Key intermediate 34, 52 and 57 were synthesized and will be converted to Cuparene in the following work through methylation, elimination and so on, which is in progress.Chapter V Chemoselective removal of phenolic TBDMS ether by organic nitrogen basesSimple organic nitrogen bases, such as Et₃N, pyridine, DBU, et al, were found to be efficient reagents for deprotection of TBDMS on phenolic hydroxyl groups in aqueous DMSO. The apparent order of efficiency of these bases is primary amine > secondary amine > tertiary amine and aliphatic nitrogen base > aromatic nitrogen base. Phenolic TBDMS ether has been cleaved selectively in the presence of alcoholic TBDMS ether in this method. The rate of deprotection is in inverse ratio to the amount of base. Catalytic amount of base did the reaction wildly and completely in enough time. This method also worked with carboxylic TBDMS esters and phenolic Ac esters. This method is high yielding, fast, clean, safe, cost-effective, and most suitable for organic synthesis.