FIRST SYNTHESES OF CAERULOMYCIN-E AND COLLISMYCIN-A AND COLLISMYCIN-C- A NEW SYNTHESIS OF CAERULOMYCIN-A

Caerulomycins produced by Streptomyces caeruleus, and collismycins mor e recently isolated from Streptomyces species, are bipyridinic molecul es endowed with antibiotic and cytotoxic activities. The first synthes es of caerulomycin E (1), as well as new syntheses of caerulomycin A ( 2), are reported. Methodologies involving efficiently controlled react ions such as metalation and cross-coupling reactions have been develop ed from 2,2'-bipyridine. The functionalization at C-6 could be achieve d 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 synth eses of collismycins A (3) and C (4).