Mitsuko Asai

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.

Emeriamine, an antidiabetic β-aminobetaine derived from a novel fungal metabolite

Abstract Emeriamine [(R)-3-amino-4-trimethylaminobutyric acid], derived from a novel fungal metabolite “emericedin” [(R)-3-acetylamino-4-trimethylaminobutyric acid], was proved to be a strong and specific inhibitor of carnitine-dependent oxidation of long chain fatty acid (IC 50 ; 3.2 × 10 −6 M) and its main inhibition site was shown to be carnitine palmitoyltransferase I located on the outer-surface of the mitochondrial inner membrane. Emeriamine also showed hypoglycemic and antiketogenic activities in a dose-dependent manner (1–10 mg/kg) when administered orally to fasted normal and diabetic animals.

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 .

Stereo-chemical studies on the sulfoxide of 5,6-cis-carbapenem antibiotics, C-19393 components

Abstract The absolute configuration at the sulfoxide of 5,6- cis -carbapenem antibiotics is discussed on the basis of chemical reactions and the CD spectral data. Some stereoisomers at the side chain were synthesized from C-19393 H 2 by the combination of hydrogenation, oxidation and Z,E -isomerization. The CD spectral studies revealed that the Cotton effects of stereoisomers at the sulfoxide indicated clear opposite signs at both 260–275 and 280–300 nm regions. Further CD spectral studies on the derivatives elucidated that these Cotton effects may reflect two chromophores; for the former region and for the latter. In conclusion, these naturally occurring 5,6- cis -carbapenem antibiotics have been shown to possess the R -configuration at the sulfoxide.

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.

Opposite chirality of pillaromycin A to tetracyclines: the X-ray analysis of Achromycin hydrochloride.

Durch Röntgen-Strukturanalyse wurde die absolute Konfiguration des Antibiotikums Achromycin ermittelt. Sie ist zu derjenigen des verwandten, aus Kulturen vonStreptomyces flavovirens stammenden Pillaromycins A entgegengesetzt.