I. A. Solomons

The chemical and physical properties of terramycin.

Terramycin is a highly active antibiotic isolated from the elaboration products of the actinomycete, SlrepIomyces rinzosus, when this microorganism is grown on suitable culture media.‘ I t has been demonstrated in our laboratories that the antibiotic has a marked effect against a wide variety of microorganisms, including many of the Gram-positive and Gram-negative bacteria, both aerobic and anaerobic, the rickettsia, and certain of the viruses.?, The present paper deals with preliminary observations on the isolation and chemical and physical properties of this antibiotic. Terramycin may be isolated from solutions by a number of methods. In the initial isolation, a culture filtrate of the microorganism was extracted with n-butanol and transferred into dilute acid to give a crude concentrate of the antibiotic. Chromatography on Florisil yielded a high potency fraction, which was purified further by extracting into butanol and re-extracting into dilute acid. Pure crystalline terramycin dihydrate of constant elemental analysis was obtained by dissolving the crude material in dilute acid, adjusting to neutrality with alkali, and repeating this procedure. The antibiotic homogeneity was demonstrated by chromatography on paper and by counter-current distribution. The crystalline antibiotic is an amphoteric substance forming crystalline acid and basic salts which are readily soluble in water. At its isoelectric point, however, terramycin is rather insoluble in water. Further, terramycin, its hydrochloride, and its sodium salt are reasonably soluble in acetone, methanol, ethanol, and other polar organic solvents. Preliminary studies on the stability of terramycin and its salts have shown that this antibiotic compares favorably with the more stable antibiotics now in common use. In the dry crystalline state, terramycin and its hydrochloride show no detectable loss in potency on prolonged storage a t room temperature. Slightly acid solutions of the antibiotic have the same marked staldity. Basic solutions are only slightly less stable.