Starting from the recently reported nonpeptidic angiotensin II (AII) receptor antagonists DuP753 (1) and Exp 7711 (2), we have designed and investigated novel substituted benzimidazoles. Systemic variation of several substituents at the benzimidazole ring positions 4-7 led to the finding that substitution in position 6 with acylamino groups results in highly active AII antagonists. Compounds with 6-membered lactam or sultam substituents in position 6 of benzimidazole showed receptor activities in the low nanomolar range but were only weakly active when given orally to rats. In contrast, analogous substitution of the benzimidazole moiety with basic heterocycles resulted in potent AII antagonists which were also well absorbed after oral application. The most active compound of this series, 33 (BIBR 277), was selected as a candidate for clinical development. On the basis of molecular modeling studies a binding model of this new class of AII antagonists to the AT1 receptor is proposed.

A set of 600 actinomycetes strains which were isolated from marine sediments from various sites in the Pacific and Atlantic Oceans were screened for the production of bioactive secondary metabolites. Marine streptomycete strains were found to be producers of well known chemically diverse antibiotics isolated from terrestrial streptomycetes, as in the case of marine Micromonospora strains. New marine members of the rare genus Verrucosispora seem to be a promising source for novel bioactive secondary metabolites as shown in the case of the abyssomicin producing strain AB-18-032.

Silaethenes (5) IR [cm-'I UV [nm] (SQ) 2239 (m), 2219 (m), 258 [a] 985 (w), 927 (w), 817 (s), 741 (s) 952 (w), 759 (s), 719 (s), 396 (w) 593 (m) (Sb) 1635 (m), 1600 (m), 259 [a] (54 1008 (m), 732 (s), 246 [a]

A new angucyclinone antibiotic, frigocyclinone, was isolated from Streptomyces griseus strain NTK 97, consisting of a tetrangomycin moiety attached through a C-glycosidic linkage with the aminodeoxysugar ossamine. Frigocyclinone showed antibacterial activities against Gram-positive bacteria. Keywords angucyclinone, screening, antibacterial, antibiotic, Streptomyces griseusIn our HPLC-diode array screening program to detect novel secondary metabolites from actinomycetes isolated from extreme habitats, extracts of culture filtrates of strain NTK 97 drew our attention. Strain NTK 97 was isolated from a terrestrial sample from Terra Nova Bay at Edmundson Point, Antarctica and produced a prominent metabolite whose UV-visible spectrum and retention time were compared with those of the more than 770 reference compounds stored in our HPLC-UV-Vis-Database [2]. The UV-visible spectrum of the dominant compound was highly similar to that of urdamycin B produced by Streptomyces fradiae [3], but their retention times differed significantly. The structure of the isolated metabolite was elucidated as a new angucyclinone with a C-glycosidic linked ossamine sugar moiety and was named frigocyclinone (1). The structure is shown in Fig. 1.Strain NTK 97 was examined for a number of key properties known to be of value in streptomycete systematics [4]. The presence of LL-diaminopimelic acid in the peptidoglycan [5] together with its colonial characteristics [6] allowed its assignment to the genus Streptomyces. More detailed taxonomic studies showed that the organism was a bone fide Streptomyces griseus strain as it produced a grey aerial spore mass on oatmeal agar, formed straigth to flexuous chains of smooth-surfaced spores and shared very high 16S rRNA gene sequences (99.6ϳ99.7%) with members of this taxon [7].Batch fermentations of Streptomyces griseus strain NTK 97 were carried out in 10-liter stirred tank fermenters (New Brunswick). The production medium consisted of glucose 1%, starch 2%, Bacto peptone 0.3%, meat extract (Oxoid) 0.3%, yeast extract (Ohly Kat G, Deutsche Hefewerke) 0.5%, and CaCO 3 0.3% in tap water (pH 7.0). The fermentation was conducted at 27°C for 118 hours with an aeration rate of 0.5 v/v/m and an agitation of 200 rpm. The

Die Kombination von Vakuumblitzpyrolyse und Matrixisolierung gestattet es, Silaethen (1 a) und seine einfach substituierten Derivate 1 bf ausgehend von den Silabicyclo[2.2.2]octadien-Vorlaufern 9 a -f zu gewinnen. Die Silaolefine l a -f sind in Argon bei 10 K stabil und kdnnen anhand ihrer charakteristischen IR-und UV-Spektren identifiziert werden. Hetero-n-Systems, 8 SilaetheneBy means of a combination of vacuum flash pyrolysis and matrix isolation silaethene ( l a ) and its simply substituted derivatives 1 bf can be prepared starting with precursors 9 af of the silabicyclo[2.2.2]octadiene type. Silaolefins 1 af a r e stable in argon at 10 K and can be identified by their characteristic IR and UV spectra.unseren Handen fiihrte die Blitzpyrolyse von 5 erst bei 1OOO"C zu einer geringfugigen Zersetzung. Im IR-Spektrum waren neben den Banden der Ausgangsverbindung nur die von wenig Ethen und die stlrkste Bande (732 cm-') von 1,l-Dichlorsilaethen (lc) zu entdecken.Ein negatives Resultat erzielten wir rnit dem Silaethenvorlaufer 6 . Unter analogen Bedingungen wie bei 5 konnten in der Matrix nur die Banden von Propen, Ethen und Acetylen registriert werden. Diese Befunde widersprechen Angaben von Auner und Grobe lo), stimmen aber mit Ergebnissen von Maltsev 9, iiberein. B. Diels-Alder-Addukte von SilacyclohexadienenSilabicyclo[2.2.2]octadiene, d. h. Diels-Alder-Addukte an Silacyclohexadiene 7 vom Typ 9, sind bereits erfolgreich fur die intermediare Ausbildung von 1 ,I-Dimethylsilaethen und Silaallen 12) eingesetzt worden. Wir haben dementsprechend die Silacyclo-Chem. Ber. 117(1984)9a 3.9 (d, 4.08 -4.30 J = 8 Hz, 1H) (m, 1H) J = 8 Hz, 1H) (m, 1H) J = 8 Hz, 1 H) (m, 1 H) J = 5 Hz, 1H) (m, 1H) J = 8 Hz, 1 H) (m, 1 H) (m, 2H, + 2-H) (m, 1H) 157