Total Syntheses of (+)-Ineleganolide and (−)-Sinulochmodin C

Described herein are the first total syntheses of the nor-furanocembranoid natural products (+)-ineleganolide (1) and (−)-sinulochmodin C (2). The synthetic strategy is predicated on a transannular Michael reaction that provides both natural products from a common macrocyclic intermediate and levera...

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Veröffentlicht in:Journal of the American Chemical Society 2022-11, Vol.144 (44), p.20539-20547
Hauptverfasser: Tuccinardi, Joseph P., Wood, John L.
Format: Artikel
Sprache:eng
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Zusammenfassung:Described herein are the first total syntheses of the nor-furanocembranoid natural products (+)-ineleganolide (1) and (−)-sinulochmodin C (2). The synthetic strategy is predicated on a transannular Michael reaction that provides both natural products from a common macrocyclic intermediate and leverages a diastereoselective radical cyclization to furnish a key bicyclic lactone. The latter is further advanced to a macrocyclic precursor via a Nozaki–Hiyama–Kishi cyclization and a one-pot furan oxidation/oxa-Michael cascade. Unexpected stereochemical nuances that guided the evolution and eventual completion of the total synthesis are discussed.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.2c09826