A new crystalline antimicrobial compound, geldanamycin, has been discovered in the culture nitrates of Streptomyces hygroscopicus var. geldanus var. nova. Geldanamycin is moderately active in vitro against protozoa, bacteria and fungi. It is also active against L-1210 and KBcells growing in culture and against the parasite Syphacia ohlevata, in vivo. The fermentation, assay, chromatography and isolation as well as its biological and chemical properties were investigated. On the basis of its physical and chemical properties, geldanamycin is a complex molecule consisting of an unsaturated moiety attached to a quinone. * This organism has been characterized by A. Dietz of these laboratories.

The synthesis of 2,8-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine (Tröger's base) from p-toluidine and of two Tröger's base analogs from other anilines by reaction with hexamethylenetetramine in trifluoroacetic acid is described. 2,3,6,7-Tetrahydro-9-methyl-2,6-di-p-tolyl-1H,5H-pyrimido[5,6,1-ij] quinazoline is formed as a secondary product in the reaction of p-toluidine and hexamethylenetetramine. One of the Tröger's base analogs, 2,8-bis(3'-pyridylmethyl)-6H,12H-5,11-methanodibenzo[b,f][1,5]d iazocine (5), is an effective inhibitor of the enzyme, thromboxane A2 (TxA2) synthase, with an ED50 of 30 ng/mL in a specified in vitro assay. Three analogs having substituents on the bridging methylene group of the bicyclic nucleus of the Tröger's base structure were prepared, but all were considerably less active than the aforementioned compound in the inhibition assay. The structures of these inhibitors of TxA2 synthase fall outside the classical structure-activity relationship that has been established for this class of enzyme inhibitors.

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Ficellomycin is a new basic antibiotic produced by Streptomyces ficellus. Ficellomycin, C13H24N8O3, inhibits the growth of gram-positive bacteria in vitro and is effective in the treatment of experimental Staphylococcus aureus infections in mice. * Taxonomic studies were done by Miss ALMA DIETZ of The Upjohn Company. The organism is designated Streptomyces ficellus UC®5438.

M. Nelsen, Jr., and V. A. Campanile for capillary glpc analyses, and Dr. D. 0. Geymer for dosimetry measurements. Also the author expresses appreciation for helpful discussions with F. F. Rust and Dr. C. D.Wagner.(9) Recent experiments using ionizing radiation as the source of radical initiation (L. H. Gale, unpublished results) demonstrate that lowering the reaction temperature for addition of HBr to neat 1-hexene to -13" yields a product with the composition: 97,Oz 1-bromo-, 2.46% 2-bromo-, and 0.50% 3-bromohexane. The low yield of 3-bromohexane indicates that the double-bond migration is practically negligible at -13" and that the bulk of the 2-bromohexane arises from ionic addition to 1-hexene. Also increasing the HBr concentration at 5" decreases the combined yield of 2-bromo-and 3-bromohexanes which is consistent with the behavior predicted by expression 10. Abstract:The unique loss of 64 mass units (sulfur dioxide) observed in the mass spectrum of tolbutamide,' the most energetically favored fragmentation, has been shown by deuterium labeling and high-resolution mass spectrometry to involve two rearrangement mechanisms. The contribution of each was assessed individually from the accurate mass measurements of the pertinent fragment ions. Some thermal decomposition of the sample was observed due to a high source temperature and/or high inlet system temperature.he mass spectrum of tolbutamide (I)' shows a loss