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 structures and absolute stereochemistries of the sanglifehrins A, B, C and D were determined unambiguously by NMR-techniques and by X-ray crystallography of the complex with cyclophilin A. Sanglifehrin A consists of a 22-membered 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 artefacts.
Fehr
T
T
Novartis Pharma Inc., Research, Department of Core Technology, Basel, Switzerland.
Kallen
J
J
Oberer
L
L
Sanglier
J J
JJ
Schilling
W
W
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D018360:Crystallography, X-Ray; D007166:Immunosuppressive Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D007783:Lactones / Q000737:chemistry; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D019696:Peptidylprolyl Isomerase / Q000378:metabolism; D013141:Spiro Compounds / Q000737:chemistry; D013302:Streptomyces / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D007166:Immunosuppressive Agents; D007783:Lactones; D018942:Macrolides; D013141:Spiro Compounds; C121329:sanglifehrin A; C121333:sanglifehrin B; C121331:sanglifehrin C; C121332:sanglifehrin D; D019696:Peptidylprolyl Isomerase