SYNTHETIC STUDIES ON DITERPENOID QUINONES WITH INTERLEUKIN-1 INHIBITORY ACTIVITY - TOTAL SYNTHESIS OF (PLUS-OR-MINUS)- AND (-TRIPTOQUINONE-A())

An efficient first total synthesis of (+/-)- and (+)-triptoquinone A ( 1), a novel diterpenoid quinone with significant inhibitory activity a gainst interleukin-1 releases, has been completed. Birch reduction of tricyclic enone (+/-)-7, prepared from known 6-methoxy-2-isopropyl-1-n aphthol (22), which is readily available in large quantities, was foll owed by immediate enolate trapping to provide silyl enol ether (+/-)-3 0. Compound 30 was converted into carboxylic acid (+/-)-4 via the corr esponding enol triflate (+/-)-31 either by sequential palladium-cataly zed carbonylation and oxidation or by direct carboxylation. The total synthesis of (+/-)-1 was completed by oxidation of (+/-)-4 with CAN in 12 steps from 22 in 19% overall yield at best. A second, enantioselec tive total synthesis of (+)-1 was accomplished via (+/-)-7, which was prepared by (-)-N- [4-(trifluoromethyl)benzyl]cinchonidinium bromide ( 33) catalyzed asymmetric Michael reaction of 6 with ethyl vinyl ketone and a subsequent aldol condensation. The absolute structures of tript oquinone B (2) and C (3), which were isolated concomitantly with tript oquinone A from the same plant sources, were established by a series o f chemical reactions based on (+)-7.