Stereoselective synthesis of 7,11-guaien-8,12-olides from santonin. Synthesis of podoandin and (+)-zedolactone A.
Photochemical rearrangement of hydroxy ester 2, easily obtained from santonin (1), afforded butenolide 4, a good starting material for the synthesis of 7,11-guaien-8,12-olides. Compound 4 has been transformed into compound 10, which has been used for the synthesis of podoandin (5) and (+)-zedolactone A (ent-6). Regioselective elimination of the acetyl group on C10 afforded directly podoandin (5). For the synthesis of ent-6, a hydroxyl group has been regio- and stereoselectively introduced at the 4alpha-position through the 3alpha,4alpha-epoxide 15. The basic hydrolysis of the 10-acetyl group in compound 18 took place with concomitant intramolecular conjugated addition of the alkoxide to the butenolide moiety to give ether 19. Cleavage of the 7,10-oxido bridge via the lactone enolate afforded (+)-zedolactone A (ent-6). This synthesis has allowed for the establishment of the absolute stereochemistry of natural zedolactone A as the enantiomer of our synthetic product.
Blay
G
G
Departamento de Química Orgánica, Facultad de Química, Universitat de Valencia, Burjassot, Spain.
Bargues
V
V
Cardona
L
L
García
B
B
Pedro
J R
JR
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000969:Antinematodal Agents / Q000138:chemical synthesis*; D003508:Cycloheptanes / Q000138:chemical synthesis*; D006868:Hydrolysis; D012500:Santonin / Q000737:chemistry*; D045789:Sesquiterpenes, Guaiane; D013237:Stereoisomerism
D000969:Antinematodal Agents; D003508:Cycloheptanes; D045789:Sesquiterpenes, Guaiane; C416072:zedolactone A; D012500:Santonin; D015107:4-Butyrolactone