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A new member of the spiroketal-containing macrolide class of fermentation-derived natural products was isolated from mycelial extracts of Streptomyces diastatochromogenes. The principal component, A82548A, was shown to possess a 22-membered macrolide ring system onto which was incorporated both a spiroketal and a hemiketal moiety. Relative stereochemistry was established by single crystal X-ray diffraction studies. Absolute stereochemistry was determined via hydrolysis of the amino sugar glycosidically linked to the aglycone, which was identified as L-kedarosamine. The overall three-dimensional structure is closely related to that of the macrolides cytovaricin, rutamycin, and ossamycin.

Avilamycin is an antibiotic complex produced by cultures of the organism Streptomyces viridochromogenes, strain NRRL 2860. These compounds belong to the orthosomycin family of antibiotics. Structural composition of the major avilamycins and several minor avilamycins are known. Nine additional minor avilamycins, designated F through N, have been isolated via semi-preparative silica gel or reverse-phase high performance liquid chromatography with final purification using a reverse-phase column loading solvent switching technique. 1H NMR and mass spectroscopy, negative ion fast atom bombardment (neg FAB) and electron impact, were used to structurally identify the avilamycins. All of the compounds were microbiologically active and similar in structure to other known avilamycins.

Over eighty N-alkyl vancomycins were synthesized by reductive alkylation of vancomycin with the appropriate aldehydes. The N-alkyl vancomycins exhibit greater antibacterial activity than the corresponding N-acyl vancomycins and the parent antibiotic. Some of these semisynthetic vancomycins are five times more active than vancomycin. The N-alkyl vancomycins also show longer elimination half-lives in rats than vancomycin.

An inhibitor of dopamine-beta-hydroxylase, designated A32390A, was isolated from the culture broth of a Pyrenochaeta species. The inhibitor showed antimicrobial activity against fungi and gram-positive bacteria. Spectroscopic analysis and chemical degradation studies indicated that the structure was 1,6-di-O-(2-isocyano-3-methylcrotonyl)-D-mannitol.

Several glycopeptides containing N-acyl groups have been isolated recently. We undertook the synthesis of N-acyl vancomycins, using the active ester method. The in vitro and in vivo antibacterial activity were evaluated, and structure-activity relationship of this series of semisynthetic vancomycins is discussed.

A58365A and A58365B, angiotensin converting enzyme inhibitors isolated from the culture filtrate of Streptomyces chromofuscus NRRL 15098, are homologous compounds of molecular formulas C12H13NO6 and C13H15NO6. The molecular similarities of the two inhibitors were established by comparison of their 1H NMR, 13C NMR, and UV spectra. Catalytic hydrogenation of A58365A led to a tetrahydro-deoxy derivative, C12H17NO5; extensive 1H NMR decoupling studies at 360 MHz allowed all the non-exchangeable protons of the derivative to be connected in a continuous substructure. This fragment was combined with information from other spectroscopic methods to suggest the structures for A58365A (1) and A58365B (2); the conclusions were confirmed by an X-ray crystallographic analysis of A58365A-dimethyl ester.

The structure of the novel nucleoside antibiotic A201A has been determined by a combination of chemical and spectroscopic methods. It is composed of 6-dimethylaminopurine, 3-amino-3-deoxyribose, p-hydroxy-alpha-methylcinnamic acid, a novel unsaturated hexofuranose and 3,4-di-O-methylrhamnose. Structures have also been assigned to several related minor factors simultaneously isolated from the fermentation broth. These unique nucleosides have very interesting similarities and differences in structure with the known antibiotics puromycin and hygromycin A.

16-Deethylindanomycin (A83094A) is a novel pyrrole-ether antibiotic produced by a strain of Streptomyces setonii. The antibiotic, which is structurally similar to indanomycin (X-14547A), is active in vitro against Gram-positive bacteria as well as coccidia.

A21978C, produced by Streptomyces roseosporus, NRRL 11379, is a complex of new acidic lipopeptolide antibiotics which inhibits Gram-positive bacteria. HPLC separation of the various components from the purified complex resulted in the isolation of A21978C1, -C2 and -C3 (major components) and -C4, -C5, and -C0 (minor components). Each of these components was fermented with cultures of Actinoplanes utahensis (NRRL 12052) to give the identical inactive peptide ("A21978C nucleus") by removal of the fatty acid acyl groups from the N-terminus. This peptide was composed of 13 amino acids: L-kynurenine, L-threo-3-methylglutamic acid, L-asparagine, L-aspartic acid (3 residues), glycine (2 residues), L-tryptophan, L-ornithine, D-alanine, D-serine and L-threonine. The amino acid sequence was determined using a combination of the Edman degradation and gas chromatography mass spectrum (GC-MS) analysis of appropriately derivatized peptides obtained from partial hydrolysis. Each major component was shown to be acylated with a branched chain fatty acid at the N-terminus and the structure of this fatty acid was determined by 1H NMR and mass spectral methods. A structure for A21978C was assigned on the basis of this degradative and physico-chemical information.