Sanglifehrins A, B, C and D, novel cyclophilin-binding compounds isolated from Streptomyces sp A92-308110 - II. Structure elucidation, stereochemistry and physico-chemical properties

A novel class of macrolides, the sanglifehrins, was discovered by screening of actinomycete strains with a cyclophilin-binding assay. The chemical str uctures and absolute stereochemistries of the sanglifehrins A, B, C and D w ere determined unambiguously by NMR-techniques and by X-ray crystallography of the complex with cyclophilin A. Sanglifehrin A consists of a 22-membere d macrocycle containing a tripeptide subunit and features in position 23 a chain of nine carbon atoms bearing a spirocyclic substituent. Sanglifehrins A and B are genuine metabolites whereas sanglifehrins C and D are artefact s.