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

26 April 2019, Version 3
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

total synthesis
alkaloid
Natural Products Chemistry
limonoids

Supplementary materials

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C3-epi XF (4)
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Diketone (8)
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pyroangolensolide (14)
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