A total synthesis of the guaiane furanosesquiterpene (±)-gnididione, a metabolite of Gnidia latifolia

Abstract

Various approaches to the furanosesquiterpene (±)-gnididione (4) are described, all of which feature the furancarboxylic acid dianion (14) as a key intermediate. The eventually successful route using the disconnection (10)→(11)+(12)+(13) proceeded via condensation of dianion (14) with 3-methylglutaric anhydride (44). Protection of the derived keto-diester (45a) as the corresponding N,N-dimethylhydrazone (45b) and Dieckmann cyclisation led to the diketo-ester (46b) after deprotection. Following stereospecific incorporation of the appropriate butanone side chain by double deprotonation of ester (46b) and alkylation using the bromo-ketone (47), the resulting dione (48) was subjected to intramolecular aldol ring closure using potassium t-butoxide as base. Saponification and decarboxylation of the aldol product (49) then gave (±)-gnididione (4).