Studies Towards The Total Syntheses Of(-)-Huperzine Q,(+)-Lycopladine B,(+)-Lycopladine C And(-)-Incarviatone A

Lycopodium alkaloids are a large family of structurally unique but related natural products.Nearly 300 compounds have been isolated so far.Owing to their complex polycyclic skeletons and diverse biological activities,the total syntheses of these alkaloids have attracted broad attention from the synthetic community in recent years.The first part of this thesis is the concise asymmetric total syntheses of three fawcettimine type alkaloids:(-)-huperzine Q,(+)-lycopladine B and(+)-lycopladine C.The first chapter was fully described the total syntheses of three Lycopodium alkaloids.The classification and biosynthetic pathway of Lycopodium alkaloids was introduced at the beginning.Then,the total syntheses of fawcettimine-type alkaloids were summarized and introduced detailly.Based on our previous work,a more concise and efficient synthetic route was designed to furnish the key 6/9 spirocyclic intermediate.The novel and chemselective carbonyl-olefin metathesis was used to construct the 5 member ring skeleton.In the late-stage,the NBS mediated enamine functionalization was used to install the aminal moiety of(-)-Huperzine Q and dienamine moiety of(+)-lycopladine B and(+)-lycopladine C.At last,we furnished the total syntheses of(-)-Huperzine Q,(+)-lycopladine B and(+)-lycopladine C in 12,14 and 15 steps respectively.(-)-Incarviatone A,a structure complexly natural product,was isolated from traditional Chinese herb Incarvillea delavayi.It has a unique polycyclic architectures with eight contiguous stereogenic centers.More importantly,preliminary biological test show it is a novel monoamine oxidase(MAO)inhibitor(IC50 29 n M).So it has a great potential for the treatment of depression,Alzheimer's disease,and other neurological diseases.The second part of this thesis is the concise asymmetric total syntheses of(-)-incarviatone A.The second chapter was focus on the total syntheses of(-)-incarviatone A.The scalable and sequential C-H activation strategy was used in the early stage synthesis.Starting from commercially available phenylacetic acid,through 4 times efficient and selective C-H activation,include the first developed diasteroselective sp3 C-H insertion reaction to construct the indane framework.In the late stage,the natural product was furnished in one step through biomimetic strategy and cascade reaction,the first asymmetric total synthesis of(-)-incarviatone A was achieved in 14 steps at last.Through the detailed mechanistic studies and all the possible intermediates and isomers formed during the biomimetic cascade process was disclose.