Efficient Enantioselective Total Syntheses of (-)-Scabronine A, G and (-)-Episcabronine A

Abstract

(–)-Scabronines G and A, and (–)-episcabronine A, which belong to cyathane diterpenoids, were isolated from a bitter mushroom, Sarcodon scabrosus. These compounds were found to be potent stimulators of nerve growth factor (NGF) synthesis. (–)-Scabronine A has the most complex structure in the scabronine family, containing six contiguous stereogenic centers in the seven-membered ring, and (–)-scabronine G possesses the least oxidized seven-membered ring among known scabronines. We have constructed the AB-ring of scabronines via a highly stereoselective oxidative dearomatization/inverse-electron-demand Diels–Alder cascade, and have achieved the total synthesis of (–)-scabronine G in 19 steps and 21% overall yield. Inspired by the biogenesis of scabronines, the first total synthesis of (–)-scabronine A has been accomplished via a highly stereoselective oxa-Michael/protonation/acetalization cascade, and the first total synthesis of (–)-episcabronine A has also been completed via another highly stereoselective cascade.