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Erythromycin A is slowly metabolized to a new antibiotic, erythromycin E (5), when incubated with fermentations of certain strains of the producing organism Streptomyces erythreus. Erythromycin E contains a novel ortho ester grouping not previously encountered in macrolide antibiotics. The isolation of erythromycin E extends and further delineates the latter stages of the erythromycin biogenetic pathway.

A further examination of the products from fermentation broths of Streptomyces violaceoniger has yielded small quantities of several lankamycin related antibiotics and metabolites. One of the antibiotics has been characterized as 3″-de-O-methyl-2″,3″-anhydro-lankamycin. The anhydro sugar of the new lankamycin, 3-methyl-4-O-acetyl-2,3,6-trideoxy-α-L-threo-hex-2-enepyranoside was also isolated as the ethyl glycoside from fermentation broths of the same organism.

Proton magnetic resonance spectra at 100 MHz were obtained for water-soluble and water-insoluble glucans from 11 strains of Streptococcus mutans . The percentages of α- D -(1→6) and non-α- D -(1→6)-, namely, α- D -(1→3)-, linkages were calculated from the anomeric-proton resonances in the 4.7-4.8 and 5.0-5.1 p.p.m. range, respectively. The average content of α- D (1→6) linkages in the polymer fractions precipitating from solution during synthesis of the glucans was generally much lower than that of fractions remaining in solution. The frequent appearance of the α- D -(1→3) resonances as doublets in the spectra suggested neighboring-group effects among the possible α- D -(1→3) and α- D -(1→6) linkage-configurations. These effects were confirmed from 100-MHz spectra of products of a dextranase-degraded, water-insoluble glucan, and a 270-MHz spectrum of an undegraded glucan. It was thus possible to assign the doublet resonances to α- D -(1→3), homogeneous, heterogeneous, and branch configurations, although complete differentiation among proportions of each configuration in the glucan chains could not be achieved.

3-O-(2″,6″-Dideoxy-α- l -ribo-hexopyranosyl)erythronolide B (6) and 3-O-(2″,6″-dideoxy-α- l -arabino-hexopyranosyl)erythronolide B (7), aberrant metabolites of erythromycin biosynthesis, have been isolated from the fermentation broth of a blocked mutant of the erythromycin producing organism Streptomyces erythreus. The defective glycosidesm, when incubated with early blocked mutants of S. erythreus capable of converting authentic erythromycin progenitors to the complete antibiotic, were unmetabolized. The probable origin of the metabolite is discussed.

The isolation and structure elucidation of a shunt metabolite of erythromycin biosynthesis, (8S)-8-hydroxy-5,6-dideoxy-5-oxoerythronolide B ( 1a ), is described. NMR and CD data reveal that the title compound and related 5-oxo derivatives ( 5 and 6 ) are conformationally homogeneous with erythronolide B ( 2 ). Consistent with this observation is the hydroxyketone-hemiacetal equilibrium present in the case of 5 . The spectroscopic data further show that 1a , (8S)8)hydroxyerythronolide B ( 12 ), and lankolide ( 13 ) have identical 8S stereochemistry.

Facile isomerization of molecular diethylstilbestrol (DES) occurs by a second order reaction on solution in organic solvents. The isomerization of the disodium salt of DES which occurs in basic methanolic solutions is a reversible first order reaction. Mechanisms of the isomerization processes of molecular and anionic DES are proposed. The estrogenic response of isolated disodium salt of cis -DES was determined to be approximately 45% of the activity observed for trans -DES using a mouse uterine weight assay. Since the trans isomer is believed to be considerably more active biologically because of its structural similarity with estradiol, it appears that the observed appreciable activity of the cis -DES test solution is a consequence of the isomerization in vivo to the trans isomer. These results may have significance in the use of DES as a ruminant growth promoter since estrogenic response appears not to be restricted solely to the amount of trans isomer content.

8- epi -erythronolide B ( 4 ) has been isolated as a product formed from the acid treatment of erythronolide B ( 3 ). When this compound was fed to a blocked mutant of the erythromycin producing organism, Streptomycetes erythreus (Abbott 2NU153), nearly quantitative yields of 3- O -(α- l -mycarosyl)-8- epi -erythronolide B ( 10 ) were obtained. The much desired 8- epi -erythromycins ( 2 ) were not realized.

The biotransformation of lankamycin and congeners darcanolide and 11-acetyllankolide by a blocked mutant of the erythromycin-producing organism Streptomyces erythreus, which cannot synthesize erythromycin without supplementation with erythromycin precursors, was investigated. Darcanolide and 11-acetyllankolide were converted into the corresponding 15-deoxy-15-oxo derivatives. Lankamycin was transformed to 15-deoxy-15-oxolankamycin, 4"-deacetyl-l5-deoxy-15-oxolankamycin and 3'-de-O-methyllankamycin. None of the derivatives possessed high antimicrobial activity.

Several previously undescribed metabolites related to lankamycin have been isolated from fermentation broths of the lankamycin-producing organism Streptomyces violaceoniger. Two of these metabolites, of weak antibacterical activity, have been characterized as 15-O-(α-L-4-O-acetyl-arcanosyl)-lankamycin and 15-deoxy-15-oxo-lankamycin. The latter antibiotic is prepared in high yield by Jones oxidation of lankamycin.

Several previously undescribed metabolites related to lankamycin have been isolated from fermentation broths of the lankamycin-producing organism Streptomyces violaceoniger. Two of these metabolites, of weak antibacterical activity, have been characterized as 15-O-(α-L-4-O-acetyl-arcanosyl)-lankamycin and 15-deoxy-15-oxo-lankamycin. The latter antibiotic is prepared in high yield by Jones oxidation of lankamycin.

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.