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Total Synthesis of (+)-Granatumine A and Related Bislactone Limonoid Alkaloids via a Pyran to Pyridine Interconversion

preprint
revised on 26.04.2019 and posted on 26.04.2019 by Timothy Newhouse, Alexander Schuppe, Yizhou Zhao, Yannan Liu
We report the first total synthesis of (+)-granatumine A, a limonoid alkaloid with PTP-1B inhibitory activity, in 10 steps. Over the course of this study, two key methodological advances were made: a cost effective procedure for ketone alpha,beta-dehydrogenation using allyl-Pd catalysis, and a Pd-catalyzed protocol to convert epoxyketones to 1,3-diketones. The central tetrasubstituted pyridine is formed by a convergent Knoevenagel condensation and carbonyl-selective electrocyclization cascade, which was followed by a direct transformation of a 2H-pyran to a pyridine. These studies have led to the structural revision of two members of this family.

Funding

NATIONAL INSTITUTES OF HEALTH (NIH)

United States Department of Health and Human Services

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History

Email Address of Submitting Author

timothy.newhouse@yale.edu

Institution

Yale University

Country

United States of America

ORCID For Submitting Author

0000-0001-8741-7236

Declaration of Conflict of Interest

None

Version Notes

Version 1.1 - computational study added

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