Affiliation:
1. Department of Pharmacy – Center for Drug Research Ludwig-Maximilians University of Munich Butenandtstraße 5–13 81377 Munich Germany
Abstract
Abstract4‐Azafluorenones are typically obtained by acid‐mediated cyclization of 2‐arylnicotinates. However, this approach fails to give 5‐oxygenated 4‐azafluorenones due to lactonization of 2‐(2‐alkoxy)phenylnicotinate intermediates. Herein, we report two modifications of established approaches to 4‐azafluorenone synthesis that, either in combination or by themselves, enable the flexible preparation of 4‐azafluorenones with diverse oxygenation patterns in the benzenoid ring. Undesired lactonization was circumvented via tert‐butyl hydroperoxide (TBHP)‐mediated radical cyclization of 2‐aryl‐3‐(hydroxymethyl)pyridines. In the absence of suitable protecting groups for phenolic intermediates, bromide substituents were regioselectively introduced as latent hydroxy groups and later converted under palladium catalysis. We present the first total syntheses of five 4‐azafluorenone alkaloids muniranine, darienine, 5,8‐dimethoxy‐7‐hydroxyonychine, 5,6,7,8‐tetramethoxyonychine, and 6,8‐dihydroxy‐7‐methoxyonychine in addition to new total syntheses of six 4‐azafluorenone alkaloids and one related pyridocoumarin alkaloid.
Subject
Organic Chemistry,Physical and Theoretical Chemistry