Protecting-group-free total syntheses of (−)-integrifolin, (+)-8-epi-grosheimin and (+)-grosheimin

Abstract

The guaianolides represent an array of complex sesquiterpene natural products with the basic 5-7-5-ring structure. An efficient diastereoselective allylation of a functionalized aldehyde with an allyl bromolactone, translactonization and aldehyde–ene reactions paved an excellent path toward the protecting-group-free divergent total synthesis of (−)-integrifolin, (+)-8-epi-grosheimin and (+)-grosheimin. The common intermediate molecule ligustrin was synthesized and further extended through various compatible reactions to more complex guaianolides. The first asymmetric total synthesis of (−)-integrifolin was achieved. The presented study should expedite access to this fascinating, bigger class of bioactive guaianolide natural products.