Studies Toward Asymmetric Synthesis Of Bisabosqual A

Bisabosqual A is a meroterpenoid isolated from Stachybotrys sp.RF-7260.Among them,this natural product has the significant inhibitory activity on squalene synthase,from Saccharomyces cerevisiae,Candida albicans,rats liver and Hep G2 cells;Since squalene synthase inhibitors can inhibit the synthesis of cholesterol in human body,they are also of some significance for the development of anti-hypercholesterolemia drugs.In addition,there is a complex structure for Bisabosqual A,as the demonbstration of a cis,cis-fused tetracyclic skeleton and five consecutive stereosteric centers,including two quaternary carbons.At present,Bisabosqual A is mainly isolated from microorganisms,which is far from meeting the needs of medicinal research for human.Therefore,the chemical synthesis of Bisabosqual A is of great significance for providing a lot of sample.However,the known synthetic route of this molecule showed long steps,low yield,and high cost,and it is highly desirable for developing a more concise and efficient synthesis method.In this thesis,a new strategy for the asymmetric synthesis of Bisabosqual A is designed.Starting with chiral perillaldehyde,the oxidative [3+2] cycloaddition as a key reaction was applied to the total synthesis of this molecule for the first time.In addition,a "stepwise[3+2]" method featuring with Michael addition and the subsequent cyclization for a construction of dihydrobenzofuran skeleton in Bisabosqual A was explorated.