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-14α,15α-epoxyschizozygine,
and (+)-α-schizozygol and the total synthesis of (+)-strempeliopine
have been accomplished in 11–12 steps from tryptamines.