Pyrrolomycin異性体の合成研究

抄録

3-(3', 5'-Dicholorosalicyloyl)-2, 5-dichloropyrrole (3) and 3-(3', 5'-dichlorosalicyloyl)-2, 4, 5-trichloropyrrole (4) was synthesized as isomers of pyrrolomycins C (1) and D (2). In order to synthesize 3-(3', 5'-dichlorosalicyloyl) pyrrole (5) which was chosen as a synthetic intermediate of 3 and 4, Friedel-Crafts acylation was carried out by the new method reported by Rokach et al. But, a major product of this reaction was 2-(3', 5'-dichlorosalicyloyl) pyrrole, an α-isomer corresponding to 5. Then, effects of acyl chlorides and Lewis acids on Friedel-Crafts acylation were studied in detail. When benzoyl, m-nitrobenzoyl and p-methoxybenzoyl chlorides reacted with N-benzenesulfonylpyrrole (6) by using anhydrous AlCl₃ as a catalyser, substitution to β-position on pyrrole ring of 6 occurred predominantly. However, in the case of the use of anhydrous SnCl₄ as a catalyser in this reaction, ratio of substitution to α-position increased. On the other hand, when 3, 5-dichloro-2-methoxybenzoyl chloride reacted with 6 in the presence of anhydrous AlCl₃, substitution to α-position occurred mainly, and in the presence of anhydrous SnCl₄, substitution to α-position further increased. Consequently, 3 and 4 were prepared from 6 by chlorination according to the Friedel-Crafts acylation reaction. Comparison of the antimicrobial activities of 3 and 4 with those of 1 and 2 revealed that 3 was equally active as 2 against Gram positive bacteria and that 3 and 4 were more active against some fungi than 1 and 2. However, the activities of 3 and 4 against Gram-negative bacteria were lower than those of 2.