Total Synthesis Of Hamigeran B

This disertation has a research on the total synthesis of Hamigeran B,mainly including the following two parts:The first part:Total synthesis of?±?-Hamigeran B.Hamigeran B is a high biological activity natural product,which has a good inhibitory effect on various viruses.It has an unique[6.6.5]tricyclic skeleton structure with three consecutive stereogenic center.In the synthesis of work,combing with the preivious research on the creaction C-C bonds in our lab,a mild and efficient phosphinamide palladacyclic catalytic system was established to complete Suzuki cross-coupling of large steric cycloalkene derivatives.The tricyclic skeleton structure was constructed featuring the intramolecular Aldol reaction in presence of Grignard reagent.By changing the protecting groups and controlling the steric hindrance,the tetrasubstitued double bond would be high enantioselectivity hydrogenolysis.Finally the study of total synthesis of?±?-Hamigeran B was completed in 14 steps.The second part:Asymmetric total synthesis of?-?-Hamigeran B.This disertation reported a new synthesis method of PHOX ligand.In the presence of EDCI and HOBt,hydroxyamides were obtained by2-?diphenyl phosphine?benzoic acid condensed with amino alcohols in high yield;And PHOX ligand was completed under the condition of PPh₃/NEt₃/CCl₄/MeCN system.New synthetic method has the advantages of simple,efficient,mild reaction conditions and high total yield.In order to complete the asymmetric total synthesis of?-?-Hamigeran B,The quaternary carbon stereogenic center was constructed by the asymmetric decarboxylation allylation reaction.Through the screening of PHOX ligands,solvents and temperature,eventually key stereogenic intermediate was obtained with 80%yield and 84%ee,it established foundation to the asymmetric total synthesis of?-?-Hamigeran B.