Structure-activity relationships of synthetic antibiotic analogs of anisomycin

A general synthetic sequence was used to synthesize a series of analogues of anisomycin, and the biological activities of the new synthetic analogues as antiprotozoals, antifungals, and antibacterials were evaluated. The synthetic antibiotics included 3 beta-acetoxy-4 alpha-hydroxy-2 beta-(p-methylb...

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Bibliographic Details
Published in:Journal of medicinal chemistry 1983-04, Vol.26 (4), p.469-475
Main Authors: Hall, Stan S, Loebenberg, David, Schumacher, Doris P
Format: Article
Language:English
Subjects:
Animals
Anisomycin - analogs & derivatives
Anisomycin - pharmacology
Bacteria - drug effects
Entamoeba - drug effects
Entamoeba histolytica
Fungi - drug effects
pharmacology
Pyrrolidines - pharmacology
Structure-Activity Relationship
Trichomonas - drug effects
Trichomonas foetus (Protozoa)
Trichomonas vaginalis
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Summary:A general synthetic sequence was used to synthesize a series of analogues of anisomycin, and the biological activities of the new synthetic analogues as antiprotozoals, antifungals, and antibacterials were evaluated. The synthetic antibiotics included 3 beta-acetoxy-4 alpha-hydroxy-2 beta-(p-methylbenzyl)pyrrolidine (1b), 3 beta-acetoxy-2 beta-benzyl-4 alpha-hydroxypyrrolidine (1c), 3 beta-acetoxy-4 alpha-hydroxy-2 beta-(m-methoxybenzyl)pyrrolidine (1d), 3 beta-acetoxy-4 alpha-hydroxy-2 beta-(o-methoxybenzyl)pyrrolidine (1e), 3 beta-acetoxy-4 alpha-hydroxy-2 beta-(alpha-methyl-p-methoxybenzyl)pyrrolidine (1f), and 3 beta-acetoxy-4 alpha-hydroxy-2 beta-(alpha-phenyl-p-methoxybenzyl)pyrrolidine (1g). The anisomycin analogues showed activity against protozoa and fungi, but this activity was restricted primarily to the p-methylbenzyl and benzyl analogues 1b and 1c. The activities dropped dramatically as the methoxy substituent was moved to the meta or ortho positions of the benzyl group (1d and 1e) or a methyl or phenyl group was attached at the alpha-benzyl carbon (1f and 1g).
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00358a003