Lei Xiaoguang group of Peking University has made important progress in the field of total synthesis of natural products of enantiokaurane tetracycline diterpene

Enantiokaurane diterpenoids are a large group of natural products of tetracycline diterpenoids with antibacterial, antiviral, antitumor and other important biological activities At present, more than 1000 members have been isolated and identified Due to its complex structure and potential biological activity, this type of natural product has attracted the attention of synthetic chemists Many famous organic chemists at home and abroad have studied the synthesis of this kind of molecules At present, most of the reported synthesis methods need to construct the four ring skeleton, especially the [3.2.1] double ring skeleton Lei Xiaoguang group of Peking University recently made important progress in the synthesis of natural products of enantiokaurane They developed a simple and efficient method to construct the enantiokaurane tetracyclic skeleton: by using the rhodium catalyzed Yu - [3 + 2 + 1] cycloaddition reaction developed by Yu Zhixiang research group of Peking University, they constructed the 6 / 6 / 6 tricyclic skeleton, and then combined with the latest palladium mediated cycloalkylation reaction to construct the [3.2.1] bicyclic skeleton The two-step strategy can be used to rapidly construct the enantiomeric kaurane and the enantiomeric beyerane skeletons with different substituents Based on this strategy, they completed the unprotected synthesis of ent-1 α - hydroxykauran-12-one and 12-oxo-9,11-dehydrokaurane in 10 and 8 steps respectively, and completed the synthesis of 12 α - hydroxy-9,11-dehydrokaurane in 10 steps, and modified its structure Through the fine regulation of the reaction precursors, the synthesis strategy can be applied not only to the efficient synthesis of different enantiomeric kaurane natural products, but also to the efficient synthesis of natural product analogues The completion of this work further elucidates the great advantages of Yu - [3 + 2 + 1] reaction in the synthesis of natural products and drug molecules with bridgehead fourth-order carbon This achievement was published online in Journal of American Chemical Society (DOI: 10.1021 / JACS 9b13722) under the title of "protecting group free syntheses of ENT kaurane dieterpenoids: [3 + 2 + 1] cycloaddition / cycloalkenylation approach" Wang Jin, a doctoral student in Lei Xiaoguang's research group, and Hong baccalaureate, Ph.D., were the co authors Professor Yu Zhixiang gave very constructive guidance to the key reactions (Yu - [3 + 2 + 1] reactions) used in this work This work was supported by the National Natural Science Foundation of China, the key R & D program of the Ministry of science and technology, the Beijing outstanding young scientists program, and the Peking University Tsinghua joint life center.