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元素有机化学国家重点实验室

Research Highlights

Achievement

【JianHua Xie's Group】Divergent Asymmetric Total Synthesis of Mulinane Diterpenoids

Release unit:SKLEOC   Release time:2017/08/24    Browse times:102


Mulinane diterpenoids were first isolated in 1990 from the aerial parts of
Mulinium crassifolium, which is a shrub growing in the north Chile and used in traditional folk medicine to treat a variety of ailments such as diabetes, bronchial, and intestinal disorders. To date, more than thirty mulinane diterpenoids have been isolated and identified. Mulinane diterpenoids possess a fused 5-6-7 tricyclic ring system with 5 to 9 contiguous carbon stereocenters, two of which are all-carbon quaternary centers. The structural complexity of mulinane diterpenoids makes their asymmetric total synthesis challenging.

Recently, Xie’s group achieved the first asymmetric total synthesis of mulinane diterpenoids. They use iridium-catalyzed asymmetric enone hydrogenation reaction recently developed from their laboratory (Org. Lett. 2017, 19, 3231-3234) to obtain key chiral intermediate. The synthetic strategy features an intramolecular Friedel-Crafts reaction to construct chiral fused 5-6-6 tricyclic motif, followed by a sequence of Birch reduction, conjugate methylation, homologation/ring-expansion reaction to furnish the desired 5-6-7 tricyclic skeleton bearing five contiguous carbon stereocenters. With this efficient strategy and late-stage functional modification or functionalization, 7 mulinane diterpenoids and 2 analogues have been synthesized in 11-15 steps in 8.6-19.9% overall yield. This work further demonstrates that the use of asymmetric catalysis can significantly improve the efficiency of asymmetric total synthesis of nature products.

Link: http://onlinelibrary.wiley.com/wol1/doi/10.1002/anie.201706994/abstract