X-ray analysis of 9-propionylmaridomycin III iodo adduct.

Abstract

The complete three dimensional structure of 9-propionylmaridomycin III (PMDM III) has been determined by the X-ray analysis of its iodo adduct. This is the first case that the structure of the intact 16-membered ring marcrolide has been determined by the X-ray analysis. Hydrophilic substituent groups of the 16-membered macrocyclic ring of PMDM III lie on one side of the ring, while the hydrophobic substituents are directed to the other side of the ring. This characteristic arrangement of the substituents gives the macrocyclic ring of PMDM III two physicochemically different faces, which have previously been pointed out in the case of the 14-membered ring of erythromycin A. Similar spatial arrangement of substituents on the macro ring is also found in the conformation of demycarosyl isoleucomycin A3 elucidated by X-ray analysis of its hydrobromide. The spatial interrelation of 6-formylmethyl, 2'-hydroxyl and 3'-dimethylamino groups, which have been known most important substituents for the biological activities of the 16-membered ring macrolide antibiotics, is strikingly similar between PMDM III and demycarosyl isoleucomycin A3.