マクロライド系抗生物質の構造

抄録

Macrolide antibiotics are widely known as the ionophoric substances which can form 1:1 complexes selectively with K⁺ ion and carry it through artificial and biological membranes. Molecular structures in crystals and molecular conformations in solutions are described for valinomycin and nactins, both in free and complexed states. Valinomycin molecule (oval shaped) possesses an approximate center of symmetry in the crystal, and the structure is stabilized by six intramolecular H-bonds; the four of those are 4→1 type H-bond and the rests are 5→1 type. In non-polar solvents, valinomycin possesses C₃ symmetry, in which six 4→1 type intramolecular H-bonds are observed (A₂ form). The structure A₂ is also observed in the K⁺-valinomycin complex, in which six ester carbonyl oxygen atoms are directed to K⁺ ion forming an octahedron of coordination. In the crystals of nactins, on the other hand, the molecular shape of dinactin (cradle; C₁ symmetry) is markedly different from those of nonactin (torus; C₂ and an approximate S₄ symmetry) and tetranactin (propeller; C₂ symmetry), but the molecular conformation of dinactin can be regarded as a hybrid of those of the subunits in K⁺-nonactin complex and tetranactin. Intramolecular van der Waals contacts are observed in dinactin and tetranactin. In solutions, nactins are very flexible, and they have the molecular symmetry of S₄. In the K⁺-nactin complexes, four carbonyl oxygen atoms and four ether oxygen atoms are directed to K⁺ ion to establish a cubic coordination.