Unified Synthesis of the Marine Sesquiterpene Quinones (+)‐Smenoqualone, (–)‐Ilimaquinone, (+)‐Smenospongine, and (+)‐Isospongiaquinone

Four biologically attractive marine sesquiterpene quinones, (+)-smenoqualone (1), (−)-ilimaquinone (2), (+)-smenospongine (3) and (+)-isospongiaquinone (4), were efficiently synthesized in a unified manner, starting from a known trans-decalin aldehyde (6) which was accessible from (+)-5-methyl-Wieland-Miescher ketone (9) in 54% overall yield over eight steps. The overall yields of 1, 2, 3 and 4 from the starting material 6 were 37% in nine steps, 33% in seven steps, 52% in seven steps and 31% in eight steps, respectively. The key steps of the synthesis were (i) coupling of 6 to the aromatic portion 8 or 25, which constructed the requisite carbon skeleton 10 or 29 (6 + 8 → 10 in Scheme 2, 6 + 25 → 29 in Scheme 10), (ii) formation of the p-quinone moiety by salcomine oxidation of the phenol 5 or 21 (5 → 14 in Scheme 2, 21 → 20 in Scheme 10), (iii) conversion of 2 into 4 by pTsOH-induced isomerization of the C4 olefinic double bond (2 → 4 in Scheme 3), (iv) site-selective amination of the dimethoxy-p-quinone 14 by substitution of the C18 methoxy group with AcNH2 followed by alkaline hydrolysis in one-pot operation, forming 3 (14 → 3 in Scheme 5), and (v) sequential BF3·Et2O-induced rearrangement/cyclization of the olefinic decalin 23, which established the requisite tetracyclic core structure 22 with correct stereochemistries at the C5 and C10 positions in one step (23 → [V → VI → VII] → 22 in Scheme 10). The syntheses of 1 and 4 are reported here for the first time.