Biomedical subjects

P Kurath

Publications and source records attributed to P Kurath.

13 recordsLinked to original sources

PubMed1989

Synthesis and activity of nonhydrolyzable pseudomonic acid analogues.

Several series of pseudomonic acid analogues have been prepared that incorporate modified functionalities in place of the C1-C3 alpha,beta-unsaturated ester group. The inhibition of isoleucyl-tRNA synthetase and the in vitro activity of these compounds against various Gram-positive and Gram-negative strains are described. Several derivatives showed enzyme inhibition equivalent to or better than that of methyl pseudomonate (3), while lacking the hydrolyzable ester group at C1. These analogues include the corresponding phenyl ketone and the ether 12. The long-chain ketone 24 exhibited similar in vitro activity as the parent ester.

Anti-Bacterial Agents↗

PubMed1984

Lysinomicin, a new aminoglycoside antibiotic. II. Structure and stereochemistry.

The structure of lysinomicin, a new aminocyclitol antibiotic, was established as 3-epi-2'-N-(L-beta-lysyl)-4',5'-didehydro-6'-de-C-methylfortimi cin B (1) on the basis of spectral evidence and chemical degradation of the antibiotic. In the course of the degradation of 1, three additional compounds with interesting biological properties were obtained: 3-epi-2'-N-(L-beta-lysyl)-6'-de-C-methylfortimicin B (4), 3-epi-4',5'-didehydro-6'-de-C-methylfortimicin B (6) and 3-epi-6'-de-C-methylfortimicin B (7).

Aminoglycosides↗

PubMed1982

4-N-Aminoacylation of substances derived from lysinomicin.

The preparations of 4-N-glycyllysinomicin and several 4-N-aminoacyl derivatives of compounds prepared from lysinomicin are presented. The new substances have lower antimicrobial activities than the original 4-N-unsubstituted lysinomicin derivatives. This result indicates that the structure-activity relationship observed with fortimicin A and fortimicin B does not apply to the lysinomicin derivatives studied.

Acylation↗

PubMed1981

Substances derived from 4-de-N-methylfortimicin B.

The preparation of 4-de-N-methylfortimicin A analogs as well as the preparation of 4-de-N-methyl-4-N-(beta-aminoethyl)-4-N-ethylfortimicin B is reported. It was shown that the 4-N-methyl group in fortimicin analogs is essential for antibacterial activity since neither the 4-de-N-methylfortimicin A nor the 4-de-N-methyl-4-N-(beta-aminoethyl)-4-N-ethylfortimicin B exhibited useful biological activity.

Aminoglycosides↗

PubMed1980

4-N-acylfortimicins B and the preparation of fortimicin A from fortimicin B.

Selective 4-N-acylation of fortimicin B (2) has been accomplished by 4-N-acylation of 1,2',6'-tri-N-benzyloxycarbonylfortimicin B (4) followed by hydrogenolysis of the N-protecting benzyloxycarbonyl groups. In this manner, fortimicin B was converted into fortimicin A (1), and a series of 4-N-acylfortimicins B (3) was prepared for antibacterial assay. The key intermediate, 1,2',6'-tri-N-benzyloxycarbonylfortimicin B, was prepared either directly from fortimicin B or by converting fortimicin A into 1,2',6',2''-tetra-N-benzyloxycarbonylfortimicin A (6a), followed by selective hydrolysis of the 4-N-(N-benzyloxycarbonyl)glycyl group of the latter.

Acylation↗

PubMed1979

4-N-Aminoacylfortimicins E.

The conversion of fortimicin E, a minor metabolite from the Micromonospora olivoasterospora fermentation which also produces fortimicin A and fortimicin B, to four 4-N-aminoacylfortimicins E was accomplished. The new 4-N-aminoacylfortimicins E showed only weak antimicrobial activity against several Gram-negative and Gram-positive microorganisms.

Aminoglycosides↗

PubMed1978

The structures of the m-chloroperbenzoic acid oxidation products of 8,9-anhydroerythromycins A- and B-6,9-hemiacetal and of (8S)-8-hydroxyerythromycin B.

13C-NMR studies have confirmed the structures of (8S)-8-hydroxyerythromycins A- and B-6,9;9,11-acetal proposed by KROWICKI and ZAMOJSKI2,3) for the products of the m-chloroperbenzoic acid oxidation of 8,9-anhydroerythromycins A- and B-6,9-hemiacetal. The preparations of (8S)-8-methylthiomethoxy- and (8S)-8-methoxyerythromycin B-6,9;9,11-acetals are described. The latter are stable in aqueous acetic acid under conditions which convert (8S)-8-hydroxyerythromycin B-6,9;9,11-acetal into (8S)-8-hydroxyerythromycin B.

Acetates↗

PubMed1976