Total synthesis of Elisabethin A: intramolecular Diels-Alder reaction under biomimetic conditions.
We describe the first total synthesis of the marine diterpenoid elisabethin A. The synthesis uses (S)-hydroxy-2-methyl-propionate as the chiral starting material, which is elaborated into a dienyl-iodide and added to an aryl acetic acid ester via enolate alkylation. The hydroquinoid system is oxidized to the quinone which serves as the dienophile in a highly stereocontrolled intramolecular Diels-Alder addition. This IMDA reaction, which to our knowledge is the first one to employ a terminal (Z)-diene, proceeds under biomimetic conditions (water, ferrichloride as the oxidant, room temperature) with high yield and stereoselectivity. The Diels-Alder adduct is transformed into the natural product via a three-step sequence including selective hydrogenation, base-catalyzed epimerization of the cis- into the trans-decalin system and O-demethylation.
Heckrodt
Thilo J
TJ
Institut für Organische Chemie der Universität Wien, Währingerstrasse 38, A-1090 Wien, Austria.
Mulzer
Johann
J
D000818:Animals; D040761:Biomimetic Materials / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D003063:Cnidaria / Q000737:chemistry; D004224:Diterpenes / Q000138:chemical synthesis*; D019906:Nuclear Magnetic Resonance, Biomolecular
D004224:Diterpenes; C474511:elisabethin A