Structural studies on ebelactone A and B, esterase inhibitors produced by actinomycetes.

In the course of our studies on enzyme inhibitors produced by microorganisms, two potent esterase inhibitors named ebelactone A and B, were isolated from the cultured broth of the strain MG7-G1 which was closely related to Streptomyces aburaviensis1). They were determined to be new members of mycolic acid /3-lactone. As reported in our previous papers2.3), esterastin, an esterase inhibitor produced by Streptomyces lavendulae MD4-Cl, was also structurally a mycolic acid /3-lactone. Thus, again the /3-lactone structure was suggested as an active group that inhibits esterase. In this paper, we report on structural elucidation of ebelactone A and B. Ebelactone A (1a) was obtained as colorless needles1), mp 86°C, [a]20D, -221° (c 1, methanol), UV maximum at 291 nm in methanol. The molecular formula for la was established by elementary analysis and mass spectrometry as C20H34O4. In the mass spectrum, the molecular ion peak (m/z 338) and the peak of a decarboxylation product (m/z 294) were observed. The IR spectrum indicated the presence of hydroxyl (3500 cm-1), /3-lactone (1820 cm-1) and carbonyl (1695 cm-1) groups. The 1H NMR spectral analysis (Table 1) showed the presence of a partial structure CH3CHCHCHCH3. By comparison with the spectral data of the /3-lactone moiety of esterastin3) and antibiotic 1233 A4) (Table 2), the structure was shown to be A in Fig. 1. The 1H NMR spectrum (Table 1) also showed the presence of partial structures B and C in Fig. 1. The spectral data of 8-H (5 3.59, doublet of quartets) and 10-H (5 2.86, doublet of quartets) indicated that these two fragments should be linked through a carbonyl group. In the 13C NMR spectrum, two carbonyl, seven methine, two methylene, seven methyl and two olefinic carbons were observed as shown in Table 3.