Syntheses of (+)-Flabellidine and (–)-Lycodine
Biogenetically Inspired Total Syntheses of Lycopodium Alkaloids, (+)-Flabellidine and (–)-Lycodine.
J. Am. Chem. Soc. 2014;
20 October 2014 (online)
In the wake of their interesting biological activities, Lycopodium alkaloids have attracted great attention from the synthetic community. A biosynthetic pathway has been proposed, in which the skeleton is constructed via a cyclization cascade. Inspired by this hypothesis, Takayama and co-workers report a successful implementation of this strategy leading to a synthesis of (–)-lycodine and the first synthesis of (+)-flabellidine.
Subjecting B to (+)-CSA triggered a cascade resulting in the formation of four rings and three contiguous stereogenic centers. Upon one-pot debenzylation–N-Boc protection of the C and D mixture, the obtained diastereomers E and F were separated, with E being further elaborated to the target natural products (+)-flabillidine and (–)-lycodine.