Abstract
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.
Original language | English |
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Pages (from-to) | 9535-9545 |
Number of pages | 11 |
Journal | Chemistry - A European Journal |
Volume | 23 |
Issue number | 40 |
DOIs | |
State | Published - 2017/07/18 |
Keywords
- alkaloids
- cytotoxicity
- natural products
- spiro compound
- total synthesis
ASJC Scopus subject areas
- Catalysis
- General Chemistry
- Organic Chemistry