Toyokazu Kishi

Ansamitocin, a group of novel maytansinoid antibiotics with antitumour properties from Nocardia

WE have isolated a new group of ansamycin antibiotics with potent antitumour activity, from a fermentation broth of Nocardia sp. No. C-15003 (N-l) and have named it ansamitocin. Structures of ansamitocin were found to be similar to maytansine and related maytansinoids obtained from plant sources by Kupchan et al.1–4 and Wani et al.5. These comounds have strong antitumour activities, but development of production would be difficult, because plants containing maytansinoids are only harvested in tropical areas and their content in the plants is extremely low. Some attempts have been made to find a maytansinoid-producing microorganism6, but no success has been reported. We report here the microbial production, isolation and structural elucidation of these antibiotics and their antitumour activities against several experimental tumours in mice.

STRUCTURE OF MILDIOMYCIN, A NEW ANTIFUNGAL NUCLEOSIDE ANTIBIOTIC

Abstract The chemical structure of mildiomycin (1) active against powdery mildews was determined by chemical degradations and physical analyses to be 2 - [(2R, 5S, 6S) - 2 - (4 - amino - 1,2 - dihydro - 5 - hydroxymethyl - 2 -oxopyrimidin -1 - yl) - 5,6 - dihydro - 5 - L - serylamino - 2H - pyran - 6 - yl] - 5 - (3H+ - guanidino) - 2,4 -dihydroxyvalerate as shown in Chart 1. 1

The structures of macbecin I and II : New antitumor antibiotics

Abstract Macbecin I 1 , C 30 H 42 N 2 O 8 , and macbecin II 2 , C 30 H 44 N 2 O 8 , were shown to be 2,6-disubstituted benzoquinone and hydroquinone derivatives by an oxidation-reduction relationship, UV. 1 H and 13 C NMR spectra. Alkaline methanolysis of 1 gave a 2-aminobenzoquinone derivative 5 , suggesting an ansa-structure for 1 , and acid hydrolysis of 1 gave decarbamoyl products 9 , 10 and 11 , indicative of the location of carbamoyloxy group in allylic position. Spin decoupling studies on 1 , 3 and 5 clarified the partial structures [ A ], [ B ], [ C ] and [ D ]. From their mutual disposition two structures 1a and 1b , were proposed out of which 1a has been selected for the structure of 1 on the basis of the structure of oxidative degradation product 12 . X-Ray analysis of the bromoacetyl derivative of 1 confirmed the above proposed structure and determined the absolute stereochemistry of 1 and 2 .

The X-ray analysis of tolypomycinone tri-m-bromobenzoate

Bestimmung der Molekularstruktur des Tolypomycinones durch Röntgenstrukturanalyse seinerm-Bromobenzoat-Kristalle. Die auf chemischem Wege aufgeklärte Konstitution wird bestätigt und darÜber hinaus Klärung Über Konfiguration und Konformation des Tolypomycin Y erreicht.

Isolation of maridomycins and structure of maridomycin II

Das ausStreptomyces hygroscopicus isolierte neue Makrolid Maridomycin II lässt sich mit Säure Mycarcose und Mycaminose spalten. Auf Grund der Oxidation ins Carbomycin sowie der spektroskopischen Daten wurde die Struktur als II erklärt.

The structures of macbecin I and II, new antitumor antibiotics

Abstract Structures of macbecin I (1) and II (2), new antitumor antibiotics isolated from the culture broth of Nocardia sp. No. C-14919, have been elucidated as benzenoid ansamycins on the basis of chemical evidence and spectral analyses.

Structures of maridomycin I, III, IV, V and VI, macrolide antibiotics

Strukturaufklärung einer Gruppe von Antibiotika aus der Reihe der Makrolide.

Interconversion of T-2636 antibiotics produced byStreptomyces rochei var.volubilis

Mit angereicherten Enzympräparaten vonStreptomyces rochei var.volbulis sowie einigen Pilzen Hessen sich die Antibiotica T-2636 A (I) und D (III) zu C (II) beziehungsweise F (IV) reversibel desacetylieren. Die Antibiotica (III) und (IV) wurden auch mit dem EnzymS. rochei var.volubilis dehydriert.

Chemical Modification of Maridomycin, a New Macrolide Antibiotic

Maridomycin, a new macrolide antibiotic, and tetrahydromaridomycin were acylated into their mono, di, and tri acyl derivatives. These derivatives were compared with the parent antibiotic, maridomycin, for their (i) in vitro antimicrobial activities, (ii) protective effect in mice infected with Staphylococcus aureus (oral administration), (iii) blood levels attained in rats, and (iv) acute toxicity in mice (intraperitoneal administration). All the derivatives showed either the same or less activity in vitro, but 9-acyl, 9, 2′-diacylmaridomycin and 9, 13, 2′-triacetyltetrahydromaridomycin demonstrated improved therapeutic effects together with higher blood levels and low toxicity. 9-Propionylmaridomycin showed the most favorable biological properties. Images