关键词: (N,O)-螺缩酮, Aldol环化, Pratensilin, 全合成

(±)-Pratensilins are a class of natural products isolated from Streptomyces. Owing to their notable antibacterial and antitumor activities, they have been identified as research focus in the field of natural product chemistry. However, their molecular structure comprises five ring systems (A, B, C, D, and E) with the C and E rings jointly forming a characteristic (5,5)-(N,O)-spiroketal scaffold, which poses substantial synthetic challenges. To date, no reports on their chemical synthesis have been documented. To address this gap in the synthetic research of such natural products, this study undertook a total synthesis study targeting the N-methyl Pratensilin B molecule. Firstly, using copper trifluoromethanesulfonate [Cu(OTf)₂] as the catalyst and a racemic oxazoline as the ligand, the key (5,5)-(N,O)-spiroketal scaffold of the target molecule was efficiently constructed via a catalytic reaction. Subsequently, under the action of a catalytic amount of lithium hydroxide (LiOH), the B ring system was successfully constructed through an intramolecular Aldol cyclization reaction. Through the design and optimization of the aforementioned key steps, the first total synthesis of the N-methyl Pratensilin B molecule was ultimately accomplished. This study provides a viable strategy for the synthetic chemistry research of (±)-Pratensilin-type natural products and also lays a material foundation for the in-depth investigation of their subsequent biological activities.

Key words: (N,O)-spiroketal, aldol cyclization, pratensilin, total synthesis