First Syntheses of Caerulomycin E and Collismycins A and C. A New Synthesis of Caerulomycin A

Caerulomycins produced by Streptomyces caeruleus, and collismycins more recently isolated from Streptomyces species, are bipyridinic molecules endowed with antibiotic and cytotoxic activities. The first syntheses of caerulomycin E ( 1 ), as well as new syntheses of caerulomycin A ( 2 ), are reported. Methodologies involving efficiently controlled reactions such as metalation and cross-coupling reactions have been developed from 2,2‘-bipyridine. The functionalization at C-6 could be achieved by metalation of 2,2‘-bipyridine N -oxides 5 and 12 . 6-Halo-4-methoxy-2,2‘-bipyridines ( 6, 10, 11 ) became key-molecules of these different pathways, and further functionalization at C-5 allowed the first syntheses of collismycins A ( 3 ) and C ( 4 ).