The first total synthesis of potent antitumoral (±)-mafaicheenamine A, unnatural 6-fluoromafaicheenamine A and expedient synthesis of clausine E

摘要

The first total synthesis of potent antitumoral mafaicheenamine A ( 1 ) and its unnatural analogue, 6-fluoromafaicheenamine A ( 2 ) have been accomplished. An expedient synthesis of clausine E, a key intermediate in the course of synthesis of 1 and 2 , was achieved in three steps from commercially available methyl 4-amino-3-(benzyloxy)benzoate ( 10 ) by copper-catalyzed N -arylation with aryllead triacetate, followed by cyclodehydrogenation of the resultant diarylamine under palladium( II ) acetate catalysis. Moreover, palladium-catalyzed O -prenylation of clausine E and subsequent o -Claisen rearrangement under microwave irradiation rendered the advanced intermediate, C -prenylated phenol, which was eventually subjected to oxidative cyclization to construct the dihydroisocoumarin unit, leading to the synthesis of 1 and 2 in 12% and 15% overall yield, respectively, from 10 .