Fermentationof deposited cultures of Streptomyces conglobatus, known to produce the polyether antibiotic, ionomycin has resulted in the isolation and characterization of a second metabolite, conglobatin (C28H33N2O6). X-Ray analysis revealed a dimeric macrolide dilactone structure for conglobatin, similar to the structures of the mold metabolites vermiculin and pyrenophorin, from which the absolute configuration of conglobatin has been inferred. The dimer consists of two molecules of 7-hydroxy-8-oxazoyl-2,4,6-trimethyl-2-octenoic acid joined by two ester linkages.

Conversion of the monovalent polyether antibiotic monensin into a series of urethane derivatives substituted at C-26 causes a tenfold increase in the cation transporting properties of the antibiotic as well as making the resulting semisynthetic urethanes divalent ionophores. These changes must in part account for the enhanced antimicrobial activities of the urethanes. The most active derivatives are the phenylurethanes which are ten times more active in vitro against Gram-positive bacteria and unlike monensin are active against Candida albicans and Penicillium digitatum. Another novel activity exhibited by four of the urethanes was against Plasmodium berghei, the causative agent for malaria.

A novel carboxylic acid ionophore, antibiotic X-14547A, closely related to the polyether antibiotics has been isolated along with four other metabolites from fermented cultures of a new strain of Streptomyces antibiotrcus. The structure, determined by X-ray analysis of the R(+ )-l-amino-l-(4-bromophenyl)-ethane salt contained pyrrole carbonyl and trans-butadienyl chremophores in addition to the unusual tetrahydroindane bicyclic ring system. A second novel metabolite was identified as 3-ethyl-l,3-dihydro-3-methoxy-2H-indol-2-one.

chloropropiono-2',6'-xylidide (7.0 g, 0.033 mol), tis-octahydro-1//pyrindine HC1 (3.75 g, 0.03 mol), Na2C03 (7.5 g, 0.06 mol), and KI (0.1 g) in 4-methyl-2-pentanone (250 ml) was stirred and refluxed for 72 hr. After cooling, H20 was added. The organic layer was separated and dried (MgS04), and the solvent was removed in vacuo.The oily residue was converted into its HC1 salt in z-Pr20-HCl.Crystallization from z-Pr20-z-PrOH gave pure 11 (7.27 g, 72%), mp 202-203°. Anal. (C19H28N20'HC1) C, , 4,4a,5,6,7,8,(2//)-quinolinepropiono-2 ',6 -xylidide Hydrochloride (21). A suspension of 3chloropropiono-2',6'-xylidide (7.0 g, 0.033 mol), ds-decahydroquinoline HC1 (5.27 g, 0.03 mol), and NaHC03 (8.4 g, 0.1 mol) in EtOH (200 ml) was stirred and refluxed overnight. After cooling the mixture was concentrated in vacuo and 2 N aqueous HC1 was added.

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Novel polyether antibiotics X-14873A, X-14873G, and X-14873H are produced by the fermentation of Streptomyces sp. X-14873 (ATCC 31679). This report presents taxonomic studies and fermentation conditions for the antibiotic producing culture. The antibiotics are mainly active against Gram-positive bacteria. The ionophore properties of X-14873A are also characterized. Intensive search in our laboratory1~4) and others,-71 in the past decade has revealed that the biosynthesis of carboxylic acid polyether antibiotics is a widespread property among streptomycetes.