Pyrroindomycins, novel antibiotics produced by Streptomyces rugosporus sp. LL-42D005. I. Isolation and structure determination.

Pyrroindomycins A and B were isolated from fermentations of culture LL-42D005, a strain of Streptomyces rugosporus. Pyrroindomycins possess potent antimicrobial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci. Their structures have been determined by using 1- and 2-D NMR, mass spectroscopy and chemical degradations. Pyrroindomycins are the first natural products that contain the highly unsaturated pyrroloindole moiety.

Chemistry of maduramicin. I. Salt formation and normal ketalization.

The formation of monovalent and divalent salt complexes of maduramicin is described and the 13C NMR chemical shift assignments of these materials are tabulated and discussed. In the spectrum of the thallium salt, 20 of the 47 signals are split due to the thallium-carbon coupling. Similarly the preparation of both the free acid and the sodium salt complexes of the normal methyl and ethyl ketal derivatives of maduramicin are outlined. Their 13C NMR spectra are fully assigned together with discussion of displacements observed due to this derivatization.

Chemistry of maduramicin. II. Decarboxylation, abnormal ketalization and dehydration.

The behavior of the free acid and ammonium salt of maduramicin towards heat and alcohols is examined. In refluxing lower alcohols the free acid material is decarboxylated. In addition a bisketal decarboxylated compound as well as an A-ring monoketal decarboxylated derivative are formed. Heating the ammonium salt of the ionophores in suspension in water, or dissolved in inert solvents such as heptane or xylene can cause decarboxylation as well as concomitant dehydration of the F-ring. Reaction of dansyl chloride with the free acid of maduramicin can cause dehydration of the B-ring under very mild conditions.

LL-F28249 antibiotic complex: a new family of antiparasitic macrocyclic lactones. Isolation, characterization and structures of LL-F28249 alpha, beta, gamma, lambda.

A new family of antiparasitic macrolides has been isolated from Streptomyces cyaneogriseus sp. noncyanogenus. The compounds, designated LL-F28249 alpha, beta, gamma and lambda, possess potent antiparasitic activity. The isolation, purification and structure determination by spectroscopic methods are presented.

Components and degradation compounds of the avoparcin complex.

The isolation and characterization of many of the components of the avoparcin complex are described. A number of mild degradations products from this complex are similarly treated. Conditions for the analytical and preparative HPLC resolution of these materials are outlined.

Biosynthesis of the antibiotic maduramicin. Origin of the carbon and oxygen atoms as well as the 13C NMR assignments.

The biosynthesis of maduramicin alpha and beta in a culture of Actinomadura yumaensis has been studied using 13C, 14C and 18O labeled precursors. The alpha component of this recently discovered polyether antibiotic, containing forty-seven carbon atoms in a seven-ring system, is derived from eight acetate, seven propionate and four methionine molecules. The beta component which is missing one methoxy group incorporates three methionine methyl groups. The carbohydrate moiety was enriched by methionine, but not significantly by acetate or propionate. Studies of the incorporation of 13C labeled precursors permit the 13C NMR assignment of maduramicin. The origin of oxygen atoms of maduramicin has been examined by feeding [1-13C, 18O2]acetate and [1-13C, 18O2]propionate separately in the fermentation culture and the resulting doubly labeled maduramicin samples were analyzed by the isotopic shifts in the 13C NMR spectra. These results are consistent with the initial formation of a triene, which is converted to maduramicin by cyclization of the triepoxide.

New antitumor antibiotic, LL-C10037 alpha. Fermentation, isolation and structure determination.

A new antitumor antibiotic, LL-C10037 alpha was isolated from the fermentation filtrate of a Streptomyces by adsorption, partition and reverse phase column chromatography. Its chemical structure was determined by 1H NMR, 13C NMR, UV, IR and mass spectral data. LL-C10037 alpha is a gamma-aminoepoxysemiquinone and is related to the epoxyguinone class of antibiotics.