Asymmetric Total Syntheses of Schizozygane Alkaloids

The concise, collective, and asymmetric total syntheses of four schizozygane alkaloids, which feature a Pan lid-like hexacyclic core scaffold bearing up to six continuous stereocenters, including two quaternary ones, are described. A new method of dearomative cyclization of cyclopropanol onto the indole ring at C2 was developed to build the ABCF ring system of the schizozygane core with a ketone group. Another key skeleton-building reaction, the Heck/carbonylative lactamization cascade, ensured the rapid assembly of the hexacyclic schizozygane core and concurrent installation of an alkene group. By strategic use of these two reactions and through late-stage diversifications of the functionalized schizozygane core, the first and asymmetric total syntheses of (+)-schizozygine, (+)- 3-oxo-14a,15a-epoxyschizozygine, and (+)-a-schizozygol and the total synthesis of (+)-strempeliopine have been accomplished in 11-12 steps from tryptamines.

Automated summary

Through the development of a new method and key reactions, the concise, collective, and asymmetric total syntheses of four schizozygane alkaloids, including the first asymmetric synthesis, have been achieved in only 11-12 steps from tryptamines.