No abstract

EM574exerts gastrointestinalmotor stimulating (GMS) activity even after being converted to its metabolites PI and P2 in dogs. These metabolites were isolated from dog liver using a series of chromatographic procedures. Their structures were determined to be the 15-and 14-hydroxyl derivatives of EM574, respectively, by spectral analysis. Large scale preparation by microbial transformation was investigated for further evaluation of the metabolites, because the amounts obtained by oxidation with dog liver homogenate were limited.Three strains of actinomycetes, Amycolatopsis tolypophorus IFO 13151, Dactylosporangium variesporum IFO 14104 and Nocardia capreola IFO 12847, were found to have the aiming oxidative potency. HPLCanalysis of the crude extracts from these three cultures showedthat the bioactive metabolites, EM574 PI and P2 were produced. They were isolated from the culture broth with the other bioactive products EM574P3 and P4. These bioactive products were prepared by large scale cultivation. EM574P3 and P4 showed GMSactivity comparable to that of EM574 PI and P2. The structures of EM574P3 and P4 were elucidated by spectral analysis and found to be the 3"-0-demethyl derivatives of EM574P2 and EM574,respectively. Moreover, the absolute configuration at the C14 position of P2 was determined to be R by spectral analysis of the 6-membered cyclic carbonate of EM574P2.

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ChemInform Abstract ((I) which exists as an equilibrium mixture of two epimers in a ca. 1:1 ratio in aqueous solutions; antibacterial activity against Gram-positive and Gram-negative bacteria, susceptibility to β-lactamases, and affinity for penicillin-binding proteins).