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Synfacts 2021; 17(02): 0140
DOI: 10.1055/s-0040-1719302
Synthesis of Natural Products and Potential Drugs

Synthesis of (–)-Echinosporin

Contributor(s):
Erick M. Carreira
,
Manuel Freis
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
DOI: 10.1021/ja00202a068.
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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.


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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.


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Publication History

Article published online:
20 January 2021

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