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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).

The first deprotonations of oxazole and benzoxazole using lithium magnesates are described. The reactions occurred in tetrahydrofuran at room temperature using 1/3 equiv of lithium tributylmagnesate. As 2-lithiooxazole and 2-lithiobenzoxazole, lithium tri(2-oxazolyl)magnesate and lithium tri(2-benzoxazolyl)magnesate very rapidly and completely isomerized to the more stable 2-(isocyano)enolate and 2-(isocyano)phenolate type structures, respectively, a result shown by NMR analysis. The isolation of 2-substituted oxazoles and benzoxazoles in medium to good yields after electrophilic trapping was interpreted in two ways: (1) the equilibration between the open and closed structures is faster than the trapping of the open isomers, and the closed isomers are more reactive than the open ones, or (2) the open isomers react with electrophiles in a intramolecular Passerini type reaction. The nonreactivity of the 2-(isocyano)enolate type structure toward anisaldehyde in the absence of lithium bromide makes the intramolecular Passerini type reaction more plausible.

The first synthesis of caerulomycin C (1), an antibiotic produced by Streptomyces caeruleus, is reported. This molecule, which exhibits a 2,3,4,6-tetrasubstituted pyridine structure, was prepared from 3,4-dimethoxypyridine in a five-step sequence. The methodology involves metalation, transmetalation, aromatic cross-coupling, and halogen migration reactions.