158792-25-7

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An efficient synthetic process for the natural product of marine origin, collismycin type A, a potent neuroprotector agent, has been developed. This new synthetic route avoids chromatographic steps, implies an improvement cost, and provides easy access to large scale.

Collismycin A is a member of the 2,2′-bipyridyl family of natural products and structurally belongs to the hybrid polyketides-nonribosomal peptides. A gene coding for a lysine 2-aminotransferase of Streptomyces sp. CS40 (collismycin A producer) was inactivated by gene replacement. The mutant was unable of synthesizing collismycin A but it recovered this capability when picolinic acid was added to the culture medium. By feeding different picolinic acid analogs to this mutant, two new collismycin A derivatives were obtained with a methyl group at the 4 and 6 position of the first pyridine ring of collismycin A, respectively. The two compounds showed effective neuroprotective action against an oxidative stress inducer in a zebra fish model, one of them showing higher neuroprotectant activity than that of collismycin A and that of the control lipoic acid.

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 synt