Selective chemical modifications of polymyxin B

Polymyxin B (1) monohydrochloride was converted to the tetra-BOC derivatives 1b and 1c by reaction with di-tert-butyl dicarbonate. The structures of these protected intermediates were established utilizing a degradative sequence that afforded 3 and 5. A method for the deprotection 2,4-dinitrophenylamines to the free amine, utilizing a strongly basic ion-exchange resin, was developed for use in the degradative sequence. The tetra-BOC derivatives 1b and 1c were used to prepare several Polymyxin B derivatives 6–27 at the DAB1 and DAB9-γ-amine. The antibacterial activity of these selectively functionalized derivatives is reported here.