Synthetic Studies Towards The Total Synthesis Of Akuammiline Alkaloid Natural Products

This dissertation mainly focuses on the total synthesis of akuammiline natural products.Akuammiline alkaloids are a family of biogenetically related indole monoterpenoids isolated mainly from Alstonia scholaris,and have high-strained and cage-like structure of pentacyclic rings.The alkaloids contain potential biological activity,such as anti-cancer and antimalarial activity,and the mechanism is to interfere in the regulation of gene expression in immune.In the course of our synthetic studies,we developed an efficient synthetic strategy to synthsis of scholarisine K and alstolactine A.The key steps of the synthesis include:olefin metathesis to constuct D ring;Heck reaction to construct the 1,3-bridged[3,3,1]bicycle;intramolecular alkylation to constuct the C6-C7 bond;Fischer indolization to form the basic skeleton of akuammilines.The first asymmetric total syntheses of scholarisine K was accomplished in 22 steps.At the same time,acid-promoted epoxide opening/lactonization to generate the second lactone ring furnished the biomimetic synthesis of alstolactine A.The first asymmetric total syntheses of akuammiline natural product scholarisine K was accomplished in 25 linear steps from commercially available L-2-allylglycine.These results imply a biogenetic relationship between scholarisine K and alstolactine A.The syntheses described here may provide a new approach to other akuammilines and derivatives for medicinal studies.