Alkyne-based Cascade Reaction And Its Application In Total Synthesis Of Hemigossypol,Gossypol And Their Analogues

Natural products have diverse and complex achitectures and often display a variety of bioactivity,which play an important role in pharmaceutical,agricultural and biological industry.Meanwhile,their complex structures often mean a big challenge for chemical synthesis and embrace many efforts on synthetic investigations.Cascade reactions could establish complex achitectures stereoselectively in one step by avoiding isolation of reaction intermediates,which was a powerful method for efficiente synthesis of intricate natural products and pursued by synthetic chemists.Recently,cascade reactions involving alkyne have earned a rapid development.We catch this trend by using natural product scaffold oriented design and have established some practical methodology of cascade rection of alkyne and achieved the total synthesis of gossypol.This dissertation contains three parts:Part one: We designed and accomplished a cascade reaction of alkyne for generating a gold carbene intermediate which could be used in cyclopropanation and O-H bond insertion reaction.In addition,a preliminary study of ligand effects and the property of this newly formed gold carbene revealed that strongly ?-donating and weakly ?-acidic nitrogen-heterocyclic carbene ligand was vital for promoting methoxyl group leaving to generate the aromatic carbene,resulting in improved yield and selectivity.This carbene intermediate has partial carbocation-like property which should be classified into Fischer-type carbene.Part two: By using the low resonance energy of maltol to generate a dearomatic intermediate,which initiated Claisen rearrangement and Michael addition cascade reaction leading to rapid construction of large amounts of polysubstituted salicylaldehydes.Relevant mechanism investigation disclosed that an eight electron augment Claisen rearrangement of 1,2,6-triene was possible;the intermolecular 1,6-Michael addition process was closely correlated with the matching degree of energy of LUMO and HOMO between Michael acceptor and nucleophile.What's more,an analysis was given for some special rearrangements observed in experiments by using aromatic transition state theory.Part three: We have achieved total synthesis of gossypol,hemigossypol and their analogous.The synthetic route adopted a dearomatic oxidation state transfer strategy of maltol derivative,which enabled an efficient 100% atom-economic,step-economic and redox neutral reaction to construct polysubstituted salicylaldehyde.Besides,an intramolecular Alder-ene cyclization reaction was used to construct the key naphthaline scaffold at late stage.Finally,we have accomplished the total synthesis of gossypol in 16 steps.