Chemistry - A European Journal
Chemistry - A European Journal
5 years ago

Total Syntheses of Lepadiformine Marine Alkaloids with Enantiodivergency, Utilizing Hg(OTf)2-Catalyzed Cycloisomerization Reaction and their Cytotoxic Activities

Total Syntheses of Lepadiformine Marine Alkaloids with Enantiodivergency, Utilizing Hg(OTf)2-Catalyzed Cycloisomerization Reaction and their Cytotoxic Activities
Yoshiki Morimoto, Haruka Nokubo, Takeshi Kodama, Tomoyuki Koyama, Kengo Yamauchi, Momochika Kumagai, Kunihiro Matsumura, Shinnosuke Ezaki, Keisuke Nishikawa, Seiho Kikuchi
The enantioselective total syntheses of lepadiformine marine alkaloids, azatricyclic natural products isolated from marine tunicates, were completed. These alkaloids have a unique chemical structure characterized by the trans-1-azadecalin (AB ring system) fused with the spirocyclic ring (AC ring system). Here we found that a cycloisomerization reaction from functionalized linear substrates to a 1-azaspiro[4.5]decane framework corresponding to the AC ring in lepadiformines is promoted by a catalytic amount of mercury(II) triflate (Hg(OTf)2). The total syntheses of (−)-lepadiformines A and B were achieved in 28 % and 21 % overall yields, respectively, through the novel cycloisomerization reaction. The syntheses of (+)- and (−)-lepadiformine C hydrochloride salts also enabled us to determine the absolute configuration of natural lepadiformine C. It has been found that a phenomenon of enantiodivergence occurs in lepadiformine alkaloids from a single species of marine tunicate, Clavelina moluccensis. The cytotoxic activities of synthesized lepadiformine hydrochloride salts and their synthetic intermediates were evaluated. Under the sea: A phenomenon of enantiodivergence was found in lepadiformine alkaloids isolated from a single species marine tunicate Clavelina moluccensis through their syntheses. The enantioselective total syntheses have been achieved by a key mercury(II) triflate-catalyzed cycloisomerization reaction developed in our laboratory (see scheme), and cytotoxic activities of synthesized compounds were also evaluated.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201701475

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