Wang P,
Gao Y,
Ma D.
* Shanghai Institute of Organic Chemistry, P. R. of China
Divergent Entry to Gelsedine-Type Alkaloids: Total Syntheses of (–)-Gelsedilam, (–)-Gelsenicine,
(–)-Gelsedine, and (–)-Gelsemoxonine.
J. Am. Chem. Soc. 2018;
140: 11608-11612
Key words
Gelsemium alkaloids - Michael addition - aldol cyclization - pinacol rearrangement
Significance
Gelsedine-type natural products have attracted considerable interest from the synthetic
community owing to their interesting biological properties and complex architectures.
Ma and co-workers have developed and executed an elegant synthetic route culminating
in the preparation of four such alkaloids relying on an asymmetric Michael addition,
tandem oxidation-aldol cyclization, and a pinacol rearrangement.
Comment
Indole derivative B and enone E underwent conjugate addition to furnish F. Oxidation and aldol cyclization resulted in the formation of key structure G in a single pot. Cationic rearrangement of G provided the oxabicyclo[3.2.2]nonane skeleton present in all targets. (–)-Gelsedilam
was synthesized from H in four steps. (–)-Gelsemoxonine, (–)-gelsenicine, and (–)-gelsedine were accessed
via ethyl ketone J.
