ABSTRACT
The antibiotic heneicomycin (1), C44H62N2O11, was isolated from cultures of Streptomyces filipinensis as an amorphous yellow powder. Mass spectral and NMR analysis showed the compound to be a deoxy modification of aurodox (2), a member of the elfamycin antibiotic family. A marked change in mass spectral fragmentation compared to aurodox and 1H NMR couplings indicated the absence of the hydroxyl at position 30 of aurodox (position 3 of the tetrahydropyran).
Subject(s)
Anti-Bacterial Agents/isolation & purification , Streptomyces/chemistry , Anti-Bacterial Agents/pharmacology , Aurodox/pharmacology , Chemical Phenomena , Chemistry , Pyridones/isolation & purification , Pyridones/pharmacology , Structure-Activity RelationshipABSTRACT
In weakly acidic solution, the broad-spectrum antibiotic imipenem undergoes complex oligomerization initiated by intermolecular carboxyl group attack on the beta-lactam group. In weakly alkaline solution, intermolecular reaction between the beta-lactam and formimidoyl groups occurs instead. Both beta-lactam and formimidoyl groups also hydrolyze at pH-dependent rates. Complex decomposition schemes were determined in kinetic studies at pH 4.0 and 9.0-9.5 using HPLC and mathematical models. The rates of the several initial reactions, calculated as functions of pH and imipenem concentration by fitting the models to kinetic data, fully account for imipenem decomposition rates throughout the neutral pH range.
Subject(s)
Imipenem/analysis , Catalysis , Chemical Phenomena , Chemistry , Chromatography, High Pressure Liquid , Drug Stability , Hydrogen-Ion Concentration , Kinetics , Magnetic Resonance Spectroscopy , Models, Chemical , Spectrophotometry, Ultraviolet , TemperatureABSTRACT
An antimetabolite, THX, was isolated from fermentation broths of the thienamycin producer, Streptomyces cattleya, when the organism was grown in the presence of a fluorine-containing substrate. THX was subsequently identified as one of the four possible stereoisomers of 4-fluorothreonine. Inorganic fluoride or any one of a number of organofluorine compounds can be used as precursors of 4-fluorothreonine. In addition, 19F NMR has provided evidence that the organism synthesizes fluoroacetate under the same fermentation conditions. The in vitro antibacterial spectrum of 4-fluorothreonine is also presented.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Antimetabolites/isolation & purification , Fluoroacetates/metabolism , Streptomyces/metabolism , Thienamycins/biosynthesis , Threonine/analogs & derivatives , Animals , Anti-Bacterial Agents/pharmacology , Antimetabolites/pharmacology , Bacterial Infections/drug therapy , Magnetic Resonance Spectroscopy , Mice , Pseudomonas aeruginosa/drug effects , Stereoisomerism , Threonine/biosynthesis , Threonine/pharmacologyABSTRACT
Radioactive- and stable isotope-containing substrates were used to identify the biosynthetic precursors of the beta-lactam antibiotic, thienamycin, in Streptomyces cattleya. Acetate is utilized by the organism to form C(6) and C(7) of the beta-lactam ring. The two carbons of the hydroxyethyl group attached to C(6) are both derived from the methyl of methionine. The cysteaminyl side chain attached to C(2) is derived from cysteine. Selective inhibition of thienamycin and cephamycin C biosynthesis has been achieved either through the addition of metabolic inhibitors or through manipulation of the growth medium. These results suggest that the two beta-lactam antibiotics, thienamycin and cephamycin C, are formed by different biosynthetic pathways.
Subject(s)
Streptomyces/metabolism , Thienamycins/biosynthesis , Magnetic Resonance Spectroscopy , Models, ChemicalABSTRACT
The synthesis and some of the spectral properties of N2-[(S)-1-carboxy-3-phenylpropyl]-L-lysyl-L-proline (lisinopril, MK-521) are described. This compound inhibits angiotensin-converting enzyme with an IC50 of 1.2 X 10(-9) M.
Subject(s)
Dipeptides/chemical synthesis , Carbon Isotopes , Chemical Phenomena , Chemistry , Lisinopril , Magnetic Resonance SpectroscopyABSTRACT
4-Chlorobenzaldehyde 1-(4-chlorophenyl)-4(1H)-pyridinylidene hydrazone fluorusulfonate (4) was found to have excellent anticoccidial activity in chickens. The synthesis and biological evaluation of related analogues are presented. Presumably 4 shares a common mechanism of action with robenidine (25) since it was not active on a robenidine tolerant strain of E. tenella. Structural comparisons of the two molecules are presented.
