Enantioselective synthesis of the antiinflammatory agent (-)-acanthoic acid.
An enantioselective synthesis of the potent antiinflammatory agent (-)-acanthoic acid (1) is described. The successful strategy departs from (-)-Wieland-Miescher ketone (10), which is readily available in both enantiomeric forms and constitutes the starting point toward a fully functionalized AB ring system of 1. Conditions were developed for a regioselective double alkylation at the C4 center of the A ring, which produced compound 32 as a single stereoisomer. Construction of the C ring of 1 was accomplished via a Diels-Alder reaction between sulfur-containing diene 43 and methacrolein (36), which after desulfurization and further functionalization yielded synthetic acanthoic acid. The described synthesis confirms the proposed stereochemistry of the natural product and represents a fully stereocontrolled entry into an underexplored class of biologically active diterpenes.
Ling
T
T
Department of Chemistry and Biochemistry, University of California-San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
Chowdhury
C
C
Kramer
B A
BA
Vong
B G
BG
Palladino
M A
MA
Theodorakis
E A
EA
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D008958:Models, Molecular; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D007202:Indicators and Reagents; C099958:acanthoic acid