Synthesis Study Of Multifunctional Spiro[4.5] Decane Skeleton And Asymmetric Synthesis Study Of The 5-quaternary Carbon-1,4-cyclohexene Diketone Structure Unit

With the constant exploration of the valuable compounds in nature,more and more natural products with important biological activities and medicinal potentials have been disclosed Many of them have similar core skeleton structures.Therefore,synthetic chemists have been long-term commitment to the synthetic study of these skeletons,with the aim to provide a practical and convenient synthetic method for related natural products.This thesis mainly focuses on synthetic research on two significant skeleton structures.Part one:the bi-linderone core molecular skeleton-synthsis research on multifunctional spiro[4.5]decaneIn this part,we have summarized the synthetic stratigies of the natural products with multifunctional spiro[4.5]decane for two decades.Numerous reports are about simple natural products.Reports about the complex natural products are much fewer.Even some natural products,with important biological activities and complex structures,have not yet reported so far.Based on the early work of our group,we have carried out the synthesis research on multifunctional spiro[4.5]decane,with bi-linderone as the goal.Based on the Darzens/ring-expansion reaction developed previously by our group,we have synthesized two trienes efficiently.One triene with two methyl groups has 6π-electrocyclization reaction at room temperature rapidly,forming a novel spiro[4.5]decane.This discovery provides a new method to build the skeleton structure and synthesize natural products with this skeleton.Moreover,after the screening of literatures,it is found that there are very few examples of 6π-electrocyclization reaction happening at room temperature.Our observation is a meaningful supplement to the chemistry of 6π-electrocyclization reaction.The other triene with one methyl group could have 6π-electrocyclization reaction under thermal condition,generating another spiro[4.5]decane.We believe that the cyclization rate differences between two trienes should be attributed to the existence of intramolecular hydrogen bond,which can inhibit the process of 6π-electrocyclization reaction.And this will be quite meaningful to the practical application of 6π-electric cyclization reaction.Part two:the research on the asymmetric synthesis of the 5-quaternary carbon-1,4-cyclohexene diketone structure unitIn this part,we have summed up the synthetic strategies about 5-quaternary carbon-1,4-cyclohexene diketone structure unit,on the basis of the synthetic reports about this kind of natural products.We hope to develop a new asymmetric synthetic way for this structure unit.We have studied the 4-electron electrocyclic ring-opening/6π-electrocyclization process of the cyclobutene diketone alkenyl adducts and asymmetric synthesis of the structure unit through the chiral auxiliary and substrate chiral induction strategies.The results have showed that chiral imine auxiliary strategy is not effective.Fortunately,we have successfully accomplished the asymmetric building of the skeleton through the substrate chiral induction strategy,that is proved reliable by many examples.The yield for two steps reaches 50-62%,and ee value goes up to 91-97%.The success of this strategy provides not only a new way for the asymmetric synthesis of the natural products with this skeleton,but also a powerful fundation for the asymmetric synthesis of periglaucine B,a natural product,we are working on in our labaratory.In summary,we have efficiently accomplished the building of the multifunctional spiro[4.5]decane skeleton through 6π-electrocyclization reaction,which adds a new content for 6π-electrocyclization reaction.In addition,through the substrate chiral induction strategy,the 4-electron electrocyclic ring-opening/6π-electrocyclization process of the cyclobutene diketone alkenyl adducts has been successfully demonstrated as the asymmetric access to the 5-quaternary carbon-1,4-cyclohexene diketone structure unit with a moderate yield and high stereoselectivity.This opens a new synthetic pathway for the natural products with this skeleton.