| The total synthesis of natural products is very important in practical applications of chemistry.It is the frontier of organic specialization and has attracted wide attention from chemists.Since the amount of bioactive natural products isolated from nature is generally limited by the difficulty of separation,it is unable to provide a sufficient amount of biologically active natural products in time to evaluate biological activities and study the structural activity relationship.It is important to provide sufficient natural products and the ability to quickly prepare these natural structures.Botrytis cinerea was identified as the pathogen of more than 235 species of plants,and plants infected with it produced gray mold.This mold is widely distributed in the world,infecting many economic plants and causing serious agricultural losses every year.A large number of botryanes metabolites can be isolated from a lot of natural products.These compounds have been found to have a broad spectrum of biological activity,and studies showing high cytotoxicity to numerous human cancer cells have been shown.The natural products of the botryane family has such a elegant chemical structure and potential biological activity,which has attracted many bio or chemical researchers.Nevertheless,since the first product was isolated in 1974,more than 70 types of natural products have been isolated from the metabolites of Botrytis,but no research on the total synthesis of natural products of this family has been published.Until 2016,our research group developed IMDA and[3+2]cycloaddition reactions for the synthesis of Botryanes and Hypocrolide A.Based on previous studies in our group,this study carried out a total synthesis study for 4 ?-acetoxy-probotryane-9?,10?,15 ?-triol.This molecule is very challenging because it is the natural product with the highest oxidation state in the family and has a trans 5/5 bicyclic structure.Direct chemical synthesis of the 5/5/6 tricyclic skeleton with high tension of molecules in the presilphiperfolanol family is not easy,and this kind of obstacle was encountered in the preliminary synthesis work of the research group.The synthesis goal of this research group is 4?-acetoxy-probotryane-9?,10?,15?-triol,and the structure is very challenging.The purpose of this study is to develop an efficient synthetic route with high functional group tolerance,leading to the total synthesis of 4?-acetoxy-probotryane-9?,10?,15?-triol.There are currently few relevant studies in this field,and the family to which the molecule belongs has attracted the attention of many scientists in the field of biological activity.Therefore,this research has high application value and urgency.According to the previous research in our research group,it is considered difficult to directly construct the trans 5/5 fused ring.Very harsh reaction conditions are often required,which is detrimental to the replication and dense functional group structure of the target molecule.Therefore,consider using a detour.The synthesis of the molecule is completed by first constructing a trans 5/6/6 fused ring structure with a relatively low tension,and then completing the ring contraction reaction in one step gave the desired trans 5/5/6 tricyclic system.Considering the previous syntheses work of the group in the Botryanes family,it is feasible and efficient to continue the total synthesis using the known 5/6 bicyclic skeleton.It can save a lot of time required to develop a new synthetic route.Therefore,first,the 5/6 bicyclic skeleton was synthesized by the known route of the research group,and then the construction of the 5/6/6 tricyclic skeleton was completed by the ring closing metathesis reaction.After a series of functional group transformations,the synthesis of the ring-precursor precursor was achieved and the related Wolff rearrangement was explored.It will lay a research foundation for the total synthesis of 4?-acetoxy-probotryane-9?,10?,15?-triol. |
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