Stereoselective Synthesis of 7,11-Guaien-8,12-olides from Santonin. Synthesis of Podoandin and (+)-Zedolactone A

Abstract

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.

Photochemische Reaktionen als Schlüsselschritte in der Naturstoffsynthese

“…Auf diese Weise wurden mehrere 4a-Hydroxy-8,12-guaianolide [209] sowie (+)-Podoandin und (+)-Zedolacton A synthetisiert. [210] Weitere Naturstoffe, die durch photochemische Umlagerungen eines Cyclohexan-anellierten Cyclohexadienons hergestellt wurden, sind (AE )-b-Vetivon, [211] (À)-Cyclocolorenon [212] und (À)-Axisonitril 3. [213] In den Synthesen der Sesquiterpene (AE)-Oplopanon [214] sowie (AE )-a-Cadinol und (AE )-3-Oxo-aCadinol [215] [219] Durch photoinduzierte Vinylcyclopropan-Umlagerungen gelangen Totalsynthesen von (+)-a-und (+)-b-Cyperon ausgehend von (À)-Epimaalienon, [220] sowie von (AE )-Grandisol (73) [221] und (À)-D [221] Durch eine [3,3]-Verschiebung eines Bicyclo[3.2.2]nonadienons konnte (AE )-Sesquicaren hergestellt werden.…”

Anti-Babesial Compounds fromCurcuma zedoaria

“…The isolation and relative structures of 1 and 3 have been reported by Takano et al [4]. The absolute configuration of 1 was determined by Blay et al [5] by a synthetic method, but that of 3 remains unknown.…”

Corrosion News

“…The photochemical rearrangements of santonin derivatives proceeded in distinctly better yields if the lactone moiety had first been opened. The syntheses of several 4α‐hydroxy‐8,12‐guaianolides,209 of (+)‐podoandin, and of (+)‐zedolactone A were achieved in this manner 210. Additional natural products that have been generated by photochemical rearrangement of a cyclohexane‐annulated cyclohexadienone include (±)‐β‐vetivone,211 (−)‐cyclocolorenone,212 and (−)‐axisonitrile‐3 213.…”