Selective chemical modifications of polymyxin B

Polymyxin B (1) monohydrochloride was converted to the tetra-BOG derivative s Ib and Ic by reaction with di-tert-butyl dicarbonate. The structures of t hese protected intermediates were established utilizing a degradative seque nce that afforded 3 and 5. A method for the deprotection 2,4-dinitrophenyla mines to the free amine, utilizing a strongly basic ion-exchange resin, was developed for use in the degradative sequence. The tetra-BOC derivatives I b and Ic were used to prepare several Polymyxin B derivatives 6-27 at the D AB(1) and DAB(9)-gamma-amine. The antibacterial activity of these selective ly functionalized derivatives is reported here. (C) 1998 Elsevier Science L td. All rights reserved.