Synthesis and Antitubercular Activity of Berberine Derivatives

The isoquinoline alkaloid berberine (1) was isolated from the roots of Berberis aristata and its new, 13-benzyl (3-6), 13-allyl (7, 8), 8-(2-oxopropyl) (2), and 9-hydroxy (9) derivatives have been synthesized under mild conditions with good yield. The structures of the new derivatives were confirmed by spectroscopic (UV, IR, NMR, and MS) analysis. The antitubercular activity of the derivatives against Mycobacterium tuberculosis H(37)Rv was studied (microdilution assay) and compared with rifampicin as standard drug. The results demonstrated that the 4-chlorobenzyl (4), 2,4-dichlorobenzyl (5), 4-fluorobenzyl (6), and 3',3'-dimethylallyl (8) derivatives exhibited (MIC, 4-8 mu g/mL) 2-4 fold more activity than berberine (MIC, 16 mu g/mL), which is probably due to the 13-benzyl and allyl substitution in the molecule.