Asymmetric total synthesis of 19 dehydroxyl arisandilactone, a natural product of Schisandra chinensis

Nearly 60% of small molecule chemical drugs come from natural products and their analogues As an important source of innovative drugs, natural products with complex structures play an important role in the discovery of new drugs The total synthesis of natural products is very creative, difficult and challenging It is an important research field of organic chemistry and pharmaceutical chemistry Schizandraceae (source: Wikipedia) Schisandra is commonly used in the folk to treat insomnia, eliminate fatigue and calm down As a traditional Chinese medicine, Schisandrae has been used in China for thousands of years Many studies have shown that lignans are the main active components in Schisandra chinensis, but there are also a lot of nortriterpenoids in Schisandra chinensis Modern scientific research shows that a large number of nortriterpenoids in Schisandra chinensis have high neuropharmacological activity, as well as anti hepatitis, anti-cancer and anti AIDS properties, so the synthesis of these compounds has attracted the attention of many organic synthesis chemists Since 2003, more than 200 nortriterpenoids have been isolated from Schisandra chinensis by sun Handong, academician of Kunming Institute of Botany, Chinese Academy of Sciences This series of natural products have novel and complex structures, and their core carbon skeletons are mainly 7-7-bicycles, 7-6-5-bicycles, 7-8-5-bicycles, 7-8-3-bicycles, 7-9-bicycles and 7-8-3-5-bicycles All of these ring systems have high ring tension middle ring, even middle ring small ring system This kind of molecular skeleton is highly oxidized to form complex complex functional groups, and the chiral centers are densely distributed, which becomes the difficulty and challenge in synthesis Strategic reverse synthesis analysis (source: naturecommunications) recently, Yang Zhen's research group of School of chemistry and molecular engineering of Peking University adopted the bionic rearrangement reaction from 7-8-3 to 7-9, and completed the construction of these two kinds of new skeletons as well as the full synthesis of 19-dehydroxyl aristandilactone a In consideration of the conversion of biosynthesis, the group first completed 7-8-3 bicycles by using Simons Smith like cyclopropane ring expansion, olefin cyclometathesis and intramolecular [2 + 1] cycloaddition Then, under the action of Lewis acid, Mukaiyama aldol reaction and Homo Michael reaction took place in series, and γ - butyrolactone fragment was introduced in one step, and the bionic transformation from 7-8-3 to 7-9 with bridgehead double bond was completed After the adjustment of stereochemistry and oxidation state, the total synthesis of 19-dehydroxyl aristandilactone a was finished in 37 steps In many cases, total synthesis is the only way to obtain a large number of natural products and their analogues At this time, the pursuit of synthesis efficiency is no longer an abstract concept Simple steps measurement (the longest linear sequence, LLS) is not the only standard to measure the synthesis efficiency Considering the step economy and yield together, the improvement and application of the research work to some classical organic reaction methodology ensure the high efficiency of the synthesis, and further improve the diversity oriented synthesis strategy for the representative structure of the family natural products Thesis link: https://www.nature.com/articles/ncomms114233