Total Synthesis and Computational Investigations of Sesquiterpene-Tropolones Ameliorate Stereochemical Inconsistencies and Resolve an Ambiguous Biosynthetic Relationship

The sesquiterpene-tropolones belong to a distinctive structural class of meroterpene natural products with impressive biological activities, including anticancer, antifungal, antimalarial, and antibacterial. In this article, we describe a concise, modular, and cycloaddition-based approach to a serie...

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Veröffentlicht in:Journal of the American Chemical Society 2021-04, Vol.143 (15), p.6006-6017
Hauptverfasser: Bemis, Christopher Y, Ungarean, Chad N, Shved, Alexander S, Jamieson, Cooper S, Hwang, Taehwan, Lee, Ken S, Houk, K. N, Sarlah, David
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Sprache:eng
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Zusammenfassung:The sesquiterpene-tropolones belong to a distinctive structural class of meroterpene natural products with impressive biological activities, including anticancer, antifungal, antimalarial, and antibacterial. In this article, we describe a concise, modular, and cycloaddition-based approach to a series of sesquiterpene mono- and bistropolones, including (−)-epolone B, (+)-isoepolone B, (±)-dehydroxypycnidione, and (−)-10-epi-pycnidione. Alongside the development of a general strategy to access this unique family of metabolites were computational modeling studies that justified the diastereoselectivity observed during key cycloadditions. Ultimately, these studies prompted stereochemical reassignments of the pycnidione subclass and shed additional light on the biosynthesis of these remarkable natural products.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.1c02150