The total synthesis of the racemic forms of the eremophilane-type sesquiterpenoids eremophilenolide (2), tetrahydroligularenolide (3), and aristolochene (4) is described. The octalone 7 was converted via an efficient, regioselective route into the keto ester 12, which served as a common synthetic intermediate for the preparation of the three sesquiterpenoids. Successive subjection of 12 to alkylation, hydrolysis, and decarboxylation afforded the keto acid 14. Hydrogenation of the latter provided both the cis-fused keto acid 20, which was readily converted into (±)-eremophilenolide (2), and the trans-fused keto acid 15, which was similarly transformed into (±)-tetrahydroligularenolide (3). Conversion of 12 into the dithioketal 23, followed by desulfurization and treatment of the resultant olefinic ester 25 with excess methyllithium, provided the olefinic alcohol 27. Dehydration of the latter yielded (±)-aristolochene (4).
Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach