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Two groups of 3-substituted indole 1,6-9 as well as 4-substituted quinoline derivatives 2-5 and harman (10) were isolated from various species and genera of myxobacteria. They were identified by their spectroscopic data. Some of the metabolites show moderate antifungal activity. Their biosynthetic origin in myxobacteria was demonstrated for 1, 2, and 3 by incorporation of ~-[l'-'~C]tryptophan.In a screening program the myxobacterium Archangium gephyra, strain Ar T205, was noted because of its antifungal properties. The activity of the crude culture extract could be correlated with several UV-absorbing spots on TLC by bioautography with Mucor hiemalis and Pythium deburyanurn. For the isolation of the compounds responsible for the activity a 60-1 fermentation was performed in the presence of 600 ml of adsorber resin amberlite XAD-16. After standard work-up[21 the products were eluted from the resin with methanol and isolated according to Scheme 1 by two liquidhiquid partitions followed by several chromatographic steps. Thus, five compounds 1-5, besides a larger amount of Tyr-Pro dioxopipera~ine [~], were obtained in pure state. Compounds 1, 2, and 3 show moderate activity. against a variety of yeasts and fungi (Table 1). No antibacterial properties could be observed. 'H-NMR data suggest that all compounds contain a heteroaromatic and a small aliphatic moiety. 2D-NMR spectroscopy in combination with mass spectrometry immediately revealed the structures: 3-indolylacetaldoxime (l), 4-quinolylaldoxime (2), 4-(hydroxymethy1)quinoline (3), 4-quinolinecarbaldehyde (4), and 4-quinolinecarboxylic acid (5). Of these 4 and 5 were isolated in only very small yield and possibly may be artefacts formed during isolation.During our work with myxobacteria 1-3 and several other indole and quinoline derivatives were repeatedly isolated from various species and genera. They typically were detected as minor constituents during the isolation of other metabolites from selected production strains. Thus, Angiococcus disciformis, strain An d30, the producer of angiolam, myxochelin, and myxothiazol[41, also forms small amounts of 1. In addition, 3-(cyanomethy1)indole (6) and 3-hydroxyacetylindole (7)' were isolated and identified by their spec-

The structures of neoefrapeptins A to N, peptides with insecticidal activity, were elucidated. They showed a close similarity to efrapeptin. However, all neoefrapeptins contained the very rare amino acid 1-aminocyclopropane-carboxylic acid and some of them also contained (2S,3S)-3-methylproline. The neoefrapeptins are the first case, in which these amino acids are found as building blocks for linear peptides. They were identified by comparison of the silylated hydrolyzate to reference material by GC/MS (EI-mode). The sequence was elucidated using mass spectrometry (ESIϩ mode). Full scan spectra showed two fragments in high yield, even under mild ionization conditions. MS/MS spectra of these two fragments yielded fragment rich spectra from which the sequence of the compounds was determined almost completely. The proteolytic cleavage with the proteinase papain yielded products that allowed to prove the rest of the sequence and the identity of the C-terminus to efrapeptin. The proteolytic cleavage products allowed furthermore to determine the position of the isobaric amino acids, pipecolic acid and 3-methylproline in neoefrapeptin F, as well as the location of R-isovaline and S-isovaline. Papain digestion was such established as a tool for structure elucidation of peptides rich in a ,a -dialkylated amino acids. CD spectra suggested a 3 10 helical structure for neoefrapeptins A and F.

A one-step synthesis of the rare aurachin E (1) from the easily accessible aurachin C (2) and cyanogen bromide is described. 3-Bromocarbamoylquinoline (5) is formed in a side reaction with concomitant loss of the 3-farnesyl residue. In an alternative approach, aurachin D (3) was reacted with phosgene and sodium azide to form the imidazolone ring of 1 via N-acylation. Unexpectedly, the initial reaction occurred at the carbonyl group of 3 to give 1H-pyrrolo[3,2-c]quinoline 4. The reaction sequence represents a novel route to this type of compound. Aurachin E, contrary to other aurachins, combines a high in vitro antiplasmodial activity with low cytotoxicity and absence of mitochondrial respiratory inhibition.

Two new secondary metabolites, named pedein A and B, were isolated from the cell mass of the myxobacterium Chondromyces pediculatus. Their planar structures were elucidated by spectroscopic methods, in particular 2D NMR as 24-membered cyclic hexapeptides composed of a variable tryptophan residue, glycine, sarcosine and three unusual hydroxy b-and g-amino acids. The main component, pedein A, strongly inhibited the growth of yeasts and fungi, induced hemolysis of erythrocytes, and caused changes in membrane permeability of Rhodotorula glutinis. The structures of the pedeins are closely related to the large family of the microsclerodermins, which have been isolated from lithistid sponges of Microscleroderma and Theonella species. Keywords myxobacteria, pedeins, cyclic peptides, antifungal IntroductionMyxobacteria of the genus Chondromyces, suborder Sorangineae, have been shown to produce a variety of novel biologically active substances with different mechanisms of action. Thus, chondramides are inhibitors of the actin skeleton [1ϳ3], crocacin and ajudazols are mitochondrial electron transport inhibitors at different sites [4ϳ7], and apicularens are specific inhibitors of V-ATPase [8ϳ10]. Extracts of Chondromyces pediculatus, strain Cm p3 were noticed for their marked antifungal activity. HPLC/DAD/MS analysis of the extracts indicated the presence of six major components with molecular weights in the range of 781 to 924 mu of which two were correlated with the antifungal activity. The compounds responsible were isolated by column chromatography of the cell extract and named pedein A (1) and B (2). A tentative structure of 1 was depicted in the GBF Scientific Annual Report 1993 and at the international conference of microbial secondary metabolism in Interlaken 1994 [11] anticipating the structures of the related microsclerodermins [12ϳ14]. Here we describe in detail production, isolation, physicochemical properties and structure elucidation of 1 and 2 as well as biological properties of 1. Results Production and IsolationIn order to obtain smooth growth and reasonable cell densities, the producing organism had to be adapted to growth in liquid media by 4 to 8 transfers in shaken cultures. After that, the strain could be cultivated also in media based on technical substrates, e.g., Probion (single cell protein prepared from Methylomonas clarae; Hoechst AG, Frankfurt), soy flour, or oatmeal. effect of various technical substrates on the yields of 1 in 100-ml shake cultures of Chondromyces pediculatus strain Cm p3. By increasing the concentration of the technical substrates from 0.4 to 0.9% the amount of 1 usually decreased, with the exception of oatmeal, in which 1 production increased up to 11.9 mg/liter.The production of pedeins on a larger scale was performed in bioreactors containing media on the basis of different technical substrates. Yet comparable amounts of 1 as produced by cultivating strain Cm p3 in shake cultures, could not be achieved. In a 65-liter fermentation batch described in the experiment...