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-gamma-amine. The antibacterial activity of these selectively functionalized derivatives is reported here.
Weinstein
J
J
Schering-Plough Research Institute, Department of Chemistry, Kenilworth, New Jersey 07033-0539, USA.
Afonso
A
A
Moss
E
E
Miller
G H
GH
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D011112:Polymyxin B / Q000031:analogs & derivatives*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D011112:Polymyxin B