Beilstein J. Org. Chem.2020,16, 2795–2806, doi:10.3762/bjoc.16.230
-established for berberines [33][34][35][36][37][38][39][40][41][42]. Based on these general similarities between the derivatives 4a–e and the established quadruplex-binding berberine derivatives it is deduced that the berberine unit in 4a–e binds like the latter ones to the G4-DNA by terminal π-stacking
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Graphical Abstract
Scheme 1:
The structures and numbering of berberine (1a) and the alkyl-substituted derivatives 1an–en and the...
Beilstein J. Org. Chem.2019,15, 1575–1580, doi:10.3762/bjoc.15.161
agent in clinic. However, a high dosage is often required due to its low lipophilicity and bioavailability. The current study explores the structural modifications of berberines with potentially lipophilic aryl groups to address this problem. A series of 15 9-O-aryl-substituted berberines (3a–o) and one
9-O-phenylene-bridged berberine dimer (5) was synthesized by copper-catalyzed cross-coupling of tetrahydroberberrubine and aryl iodides, followed by oxidation with I2.
Keywords: arylation; berberines; cross-coupling; copper; lipophilicity; structural modification; Introduction
Berberine (BBR) is a
were subsequently converted back to the respective 9-O-arylated berberines and 9-O-phenylene-bridged berberine dimer. Oxidation with DMSO-d6 was first attempted with 2a. It showed good stability at ambient temperature and only 16% conversion to the 9-O-Ph berberine 3a was noted after 72 h of heating at