Studies On The Biomimetic Synthesis Of Fumagillin And Keramaphidin B

This thesis aims at the biomimetic total synthesis of Fumagillin and Keramaphidin B,which consists of the following two parts:In chapter 1,the biomimetic synthesis of Fumagillin was studied.Fumagillin is a sesquiterpene which has potent angiogenesis inhibition.A number of chemical synthesis stretagies of Fumagillin have been developed.However,the biosynthesis of Fumagillin has been studied on the stage of tissue culture and cell feeding experiment.It was worthwhile to develop the new biomimetic synthesis of Fumagillin.Our strategic design is based on the use of intramolecular ring-opening reaction(Grob fragmentation)as the key steps for the construction of the cyclohexane core system(Fig.1),which followed by Tang's biosynthesis hypothesis.At present,cyclohexene 1-92 was prepared by the Diels-Alder reaction from dienophile 1-82 and diene 1-91,which could be used as the substrate of intramolecular Sakurai reaction.Fig.1 Retrosynthetic analysis of FumagillinIn chapter 2,the biomimetic synthesis of Keramaphidin B was studied.Keramaphidin B was isolated from Amphimedon sp.in 1994,which has antibacterial and insect-resistant activity.Due to the unique structure,Keramaphidin B was considered to be the synthetic precursor of Manzamine alkaloids.To overcome the low yield of Baldwin's biomimetic synthesis,a new biomimetic synthesis strategy of Keramaphidin B based on the use of Michael-Aldol-Mannich annulation cascade reaction as the core step was probed(Fig.2).Currently,C13 unit 2-30 was preprared by Wittig and Michael reaction from quaternary phosphonium salt and C5 unit 2-26.Moreover,the model cascade annulation of Michael-Aldol-Mannich was successfully established to provide chemical basis for the annulation cascade reaction of C26 unit 2-38.Fig.2 Retrosynthetic analysis of Keramaphidin B...