235757-86-5Relevant academic research and scientific papers
Total syntheses of (-)-lycoricidine, (+)-lycoricidine, and (+)- narciclasine via 6-exo cyclizations of substituted vinyl radicals with oxime ethers
Keck, Gary E.,Wager, Travis T.,Duarte Rodriquez, J. Felix
, p. 5176 - 5190 (1999)
The development of an approach to the total synthesis of the title alkaloids is described. The approach utilizes as the key strategic element a stereoselective 6-exo radical cyclization of a vinyl radical to an O- benzyloxime radical acceptor group. The vinyl radical was itself generated by regioselective addition of phenylthiyl radical to a disubstituted alkyne. The regiochemical issues of such additions, which result in different outcomes with tri-n-butylstannyl radicals and phenylthiyl radicals, are discussed. The first such synthesis described, that of (-)-lycoricidine, proceeded in 14 steps and 11% overall yield from 10 and served to develop the radical chemistry required. A second-generation synthesis, this time of the natural (+) enantiomer, was developed using insights gleaned from the first study and proved much more efficient, providing the target alkaloid in nine steps and 44% overall yield. This approach was then employed in the more demanding case of (+)-narciclasine. Several problems arising due to the more electron rich aromatic moiety present in this structure are described. The synthesis developed to deal with these aspects afforded (+)-narciclasine in 12 steps and 26% overall yield.
