A83016F, a new member of the aurodox family.

A new member of the aurodox family of antibiotics, A83016F, has been isolated from an unidentified actionmycete designated A83016. The structure and relative stereochemistry of A83016F were elucidated by NMR examination of the parent compound and its diacetate derivative. A83016F exhibits only weak antimicrobial activity.

Comparison of the Tu elongation factors from Staphylococcus aureus and Escherichia coli: possible basis for elfamycin insensitivity.

In a previous study (C. C. Hall, J. D. Watkins, and N. H. Georgopapadakou, Antimicrob. Agents Chemother. 33:322-325, 1989), the elongation factor Tu (EF-Tu) from Staphylococcus aureus was found to be insensitive to a series of kirromycin analogs which were inhibitory to the EF-Tu from Escherichia coli. In the present study, the EF-Tu from S. aureus was partially purified and characterized. Its apparent molecular mass was approximately 41,000 Da, and the enzyme copurified with EF-Ts (molecular mass, 34,000 Da). S. aureus EF-Tu differed from its E. coli counterpart in that it bound negligible amounts of [3H]GDP, in addition to being insensitive to pulvomycin and aurodox (50% inhibitory concentrations, approximately 100 and 1,000 microM, respectively, versus 2 and 0.2 microM, respectively, for E. coli). The results are consistent with the formation of a stable EF-Tu.EF-Ts complex that affects the interaction of EF-Tu with guanine nucleotides and inhibitors.

Antibiotic SB22484: a novel complex of the aurodox group. I. Taxonomy of the producing organism, isolation of the antibiotics and chemical and biological characterization.

Antibiotic SB22484 is a novel member of the aurodox type antibiotic group produced in submerged-fermentation cultures of Streptomyces sp. NRRL 15496. The antibiotic complex is composed of two pairs of isomers with MW's of 752 and 766. The individual isomers, which were separated by preparative HPLC, equilibrate to a mixture of the isomer pair when left in aqueous solution. In vitro, SB22484 antibiotics strongly inhibited neisseriae and were also active against Streptococci, Ureaplasma urealyticum and Haemophilus influenzae.

Antibiotic SB22484: a novel complex of the aurodox group. II. Structure elucidation of the four factors.

SB22484, active against Neisseriae gonorrhoeae and Neisseriae meningitidis, is a complex of four factors, designed 1 through 4, which from two pairs of isomers, 1 and 3, and 2 and 4. Factors 1 and 3 account for 65% of the complex, factor 3 being the predominant one. On the basis of the existing and implemented correlations between structure and physico-chemical characteristics (UV and IR spectroscopies, ionization properties, MS as FAB and as negative and positive CI, 1H NMR spectroscopy as 2D COSY and NOESY) in the aurodox field, the complete structures were assigned. Factor 3 can be described as N-[7-[5(R)-[7-[1,2-dihydro-4-hydroxy-1H-2-oxo-3-pyridinyl]-6-methyl- 7-oxo-1(E),3(E),5(E)-heptatrienyl]tetrahydro-3(S),4(R)-dihydrox yfuran-2 (S)-yl]-6(S)-methoxy-5,7(R)-dimethyl-2(E),4(E)-heptadienyl]-alpha (S)-methyl-5(S)-methyltetrahydro-2(S),4(S or R)-dihydroxy-6(S)-[1(E), 3(Z)-pentadienyl]-2H-pyran-2-acetamide. Factor 1 is an epimer of factor 3 with the opposite configuration at the anomeric center. Factors 2 and 4 have an ethyl group instead of the methyl group alpha to the acetamide moiety and are in the same stereochemical relationship as the pair 1 and 3.

Synthesis and in vitro activity of aurodox carbamoyl-methyl ether and aurodox 2,4-dinitrophenylhydrazone.

The synthesis of aurodox carbamoyl-methyl ether and aurodox 2,4,-dinitrophenylhydrazone from aurodox sodium salt is described. Both synthetic analogs were found to have virtually the same ability of the original antibiotic to inhibit poly(U)-directed poly(phenylalanine) synthesis in the in vitro system of E. coli. This indicates that derivatization at the acid hydroxy and cheto functions does not affect the protein synthesis inhibitory activity of aurodox.

Antibiotic X-5108. IX. Chemical conversion of mocimycin to aurodox and derivatives of aurodox, goldinamine and mocimycin.

Mocimycin was converted to the acylesters by selective acylation of the hydroxyl group of the 4-hydroxy-1-methyl-2(1H)pyridinone moiety. Subsequent N-methylation at the nuclear nitrogen and removal of the protective group from the resulting reaction products afforded aurodox. Mono-O-acetylmocimycin and several analogous aurodox esters thus prepared possess antibacterial activity in vitro and growth-promotion properties in poultry. Esters of aurodox involving the hydroxyl group of the 4-hydroxy-1-methyl-2(1H)pyridinone moiety are activated. Accordingly, acetic acid treatment of the aurodox esters generates O-acylgoldinamines which undergo transacylation furnishing N-acylgoldinamines. Alternatively, N-acylgoldinamines can be prepared by selective mono--o-arylsulfonylation of aurodox, liberating o-arylsulfonylgoldinamine by treatment with acetic acid followed by N-acylation and removal of the protective arylsulfonyl group. A third approach to N-acylgoldinamines consists in direct N-acylation of goldinamine itself which is prepared by acetic acid treatment of aurodox. None of these derivatives prepared, however, exhibited significant antimicrobial or growth-promoting properties, suggesting that goldinonic acid moiety, or a closely related derivative thereof, is required for biological activity.