ChemInform Abstract: Synthetic Studies on Diterpenoid Quinones with Interleukin-1 Inhibitory Activity. Total Synthesis of (.+-.)- and (+)-Triptoquinone A.

Abstract

An efficient first total synthesis of (±)- and (+)-triptoquinone A (1), a novel diterpenoid quinone with significant inhibitory activity against interleukin-1 releases, has been completed. Birch reduction of tricyclic enone (±)-7, prepared from known 6-methoxy-2-isopropyl-1-naphthol (22), which is readily available in large quantities, was followed by immediate enolate trapping to provide silyl enol ether (±)-30. Compound 30 was converted into carboxylic acid (±)-4 via the corresponding enol triflate (±)-31 either by sequential palladium-catalyzed 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, enantioselective total synthesis of (+)-1 was accomplished via (+)-7, which was prepared by (-)-N-[4-(trifluoromethyl)benzyl]cinchonidium bromide(33) catalyzed asymmetric Michael reaction of 6 with ethyl vinyl ketone and a subsequent aldol condensation