Concise Total Syntheses of Phleghenrines A and C

26 May 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


The phleghenrine alkaloids were isolated from Phlegmariurus henryi Ching in scare amount and have shown potent and selective acetylcholinesterase inhibition activity. Structurally, they have a distinct and complex tetracyclic skeleton featuring a bicyclo[3.2.2]nonene core fused with a 2-pyridone or its derivative. Herein, we report concise total syntheses of phleghenrines A and C from commercially available starting materials in only 7 and 8 steps, respectively. The key steps in our approach include an inverse electron-demand Diels-Alder reaction between a masked o-benzoquinone and a N-protected enamine to prepare one key intermediate with a bicyclo[2.2.2]octenone core, a Büchner–Curtius–Schlotterbeck one-carbon insertion to expand the bicyclo[2.2.2]octenone to a bicyclo[3.2.2]nonenone, and the Trauner’s modified 2-pyridone synthesis to install the 2-pyridone moiety.


total synthesis
phleghenrine alkaloid
Diels-Alder reaction
oxidative dearomatization
one-carbon insertion

Supplementary materials

Supporting Information_Phleghenrines A and C
Experimental procedures, data, and NMR spectra


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