Smith III AB,
*,
Sulikowski GA,
Fujimoto K.
University of Pennsylvania, Philadelphia, USA
Total Synthesis of Natural (-)-Echinosporin. Determination of the Absolute Configuration.
J. Am. Chem. Soc. 1989;
111: 8039-8041
Key words
(–)-echinosporin - [2+2] photocycloaddition - palladium catalysis - carbomethoxylation - Davis hydroxylation - dehydrogenation - Parikh–Doering oxidation - Mitsunobu reaction
Significance
(–)-Echinosporin is produced by Streptomyces echinosporus MK-213, features antibiotic and antitumor activity, and was isolated by Hirayama and co-workers in 1981. In 1989, Smith and co-workers reported the enantioselective synthesis of (–)-echinosporin and determined its absolute configuration. The synthesis relies on an [2+2] photocycloaddition and an oxidation–cyclobutanol fragmentation tactic. Final Mitsunobu lactonization provided (–)-echinosporin.
Comment
Dihydrofuran C, obtained from ester A in eight steps, was combined with cyclopentenone through a [2+2] photocycloaddition to provide ketone E. Pd-catalyzed carbomethoxylation and hydroxylation resulted in α-hydroxy ester F. Lactone I was subjected to oxidation–fragmentation conditions to give lactol K which was converted to (–)-echinosporin via an intramolecular Mitsunobu reaction.
