Asymmetric Total Syntheses of Schizozygane Alkaloids

J Am Chem Soc. 2021 Dec 1;143(47):19975-19982. doi: 10.1021/jacs.1c10279. Epub 2021 Nov 19.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't