Abstract
Esterastin (1, C_<28>H_<46>N_2O_6) which has been isolated from the culture of Streptomyces lavendulae No. MD4-C1 exhibits a strong inhibiton against pancreatic esterase. Methanolysis of 1 with 0.01N NaOH in methanol at room temperature afforded a δ-lactone (3, m/e 350, C_<22>H_<38>O_3), a methyl ester (7, m/e 383, (M+1)^+) and L-N^α-acetylaspartimide (8). Mild hydrolysis of 1 with 0.01N NaOH in aqueous dioxane at room temperature gave a β-lactone (10, m/e 350) and N^α-acetyl-L-asparagine. Mild hydrolysis of tetrahydroesterastin (2) afforded a tetrahydro derivative (13, m/e 355, (M+1)^+) of 10. The β-lactone in 13 was decarboxylated at 200℃ into an E-olefin (14, m/e 310) with retention of the initial geometry of the β-lactone. Periodate-permanganate oxidation of 14 gave L-3-hydroxymyristic acid and enanthic acid. Therefore, the structure of 14 was decided to be (7E,10S)-7-heneicosen-10-ol. From the results of PMR spectral analysis and periodate-permanganate oxidation, the absolute structures of 3, 7 and 10 were determined. The stereochemistries of two Z-olefins and the S-configuration at C-3 were confirmed by PMR spectra. Therefore, the absolute structure of 1 can be proposed to be (2S, 3S,5S,7Z,10Z)-5-[(S)-2-acetamido-3-carbamoylpropionyloxy]-2-hexyl-3-hydroxy-7,10-hexadecadienoic lactone. Esterastin (1) is the first mycolic acid β-lactone produced by Streptomyces.
