Preparation and biological evaluation of novel leucomycin analogs derived from nitroso Diels-Alder reactions.
A series of 10,13-disubstituted 16-membered macrolides was synthesized using nitroso Diels-Alder reactions of leucomycin A7. Despite the extensive constituent functionalities in leucomycin, the hetero cycloaddition reactions proceeded in a highly regio- and stereoselective fashion. Subsequent chemical modifications of the nitroso cycloadducts, including N-O bond reduction, were also conducted. Most leucomycin derivatives retained antibiotic profiles similar to leucomycin A7, and, in contrast to leucomycin itself, several exhibited moderate antiproliferative and cytotoxic activity.
Yang
Baiyuan
B
Department of Chemistry and Biochemistry, University of Notre Dame, 251 Nieuwland ScienceHall, Notre Dame, Indiana 46556, USA.
Zöllner
Tina
T
Gebhardt
Peter
P
Möllmann
Ute
U
Miller
Marvin J
MJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D015939:Kitasamycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D051379:Mice; D009603:Nitroso Compounds / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D009603:Nitroso Compounds; D015939:Kitasamycin