Kazuteru Yokose

NEW α-AMYLASE INHIBITOR, TRESTATINS

Trestatin complex which exhibited a potent inhibitory activity on various alpha-amylases has been isolated from the culture filtrate of Streptomyces dimorphogenes nov. sp. NR-320-OM7HB. Three major components, trestatins A, B and C, have been purified by adsorption and ion-exchange chromatography. Their spectral and chemical properties suggested that trestatins were novel basic oligosaccharide homologues each characterized by the possession of a trehalose moiety at the non-reducing end of the molecule.

Structure of a novel phospholipase C inhibitor, vinaxanthone (Ro 09-1450), produced by penicillium vinaceum

Abstract Vinaxanthone is a novel phospholipase C inhibitor produced by Penicillium vinaceum Gilman and About NR6815. Its structre (MW 576, C28H16O14) has been elucidated as a polycyclic xanthone with poly acidic functional groups based on various NMR studies including HMBC, COLOC, 2D-INADEQUATE and selective 1D-INADEQUATE.

Comparative Antitumor Activity and Intestinal Toxicity of 5′-Deoxy-5-fluorouridine and Its Prodrug Trimethoxybenzoyl-5′-deoxy-5-fluorocytidine

N4‐Trimethoxybenzoyl‐5′‐deoxy‐5‐fluorocytidine (Ro 09–1390), a prodrug of the cytostatic 5′‐deoxy‐5‐fluorouridine (5′‐DFUR), was synthesized with the aim of reducing of the dose‐limiting toxicity of 5′‐DFUR, which is diarrhea. In mice bearing Lewis lung carcinoma, 5′‐DFUR given po produced a substantial amount of 5‐fluorouracil (5‐FU) in the intestinal tract as well as in tumors, where the enzyme pyrimidine nucleoside phosphorylase, essential for conversion of 5′‐DFUR to 5‐FU, is predominantly located. With the oral administration of Ro 09–1390 only a small amount of 5‐FU was formed in the intestine; however, the administration of Ro 09–1390 and 5′‐DFUR at the same dose produced similar amounts of 5‐FU in tumor tissues. These differences in metabolism were reflected in their toxicity and antitumor efficacy. The administration of 5′‐DFUR resulted in damage to the intestinal mucosal membrane and diarrhea in normal mice, whereas Ro 09–1390 was much less toxic to the intestinal tract. As regards antitumor activity, Ro 09–1390 and 5′‐DFUR at equivalent doses inhibited the growth of Lewis lung carcinoma to similar extents. Since Ro 09–1390 was much less toxic to the intestinal tract than 5′‐DFUR, mice bearing Lewis lung carcinoma could be given Ro 09–1390 daily over a longer period and at a higher dose, resulting in a longer survival time.

Structure of cyclothiazomycin, a unique polythiazole-containing peptide with renin inhibitory activity. Part 2. Total structure

Abstract Structure of cyclothiazomycin, a novel renin inhibitor isolated from cultured broth of Streptomyces sp . NR0516, was determined to be a unique polythiazole-containing peptide related to thiostrepton and noshiheptide. Its structure including stereochemistry was established based on NOESY experiments.

Structure of cyclothiazomycin, a unique polythiazole-containing peptide with renin inhibitory activity. Part 1. Chemistry and partial structures of cyclothiazomycin

Cyclothiazomycin is a novel renin inhibitor produced by Streptomyces sp.NR0516 (IC50 1.66μM). Its molecular formula was determined to be C59H64H18O14S7 (MW .1472) based on high-resolution FAB mass and NMR spectroscopy. Five fragments of cyclothiazomycin containing thiazole, thiazoline, heterocyclic chromophore were clarified by extensive 2D-NMR experiments.

Structural elucidation of arthrobacilins A, B and C, structurally unique secondary metabolites of A microorganism

Abstract Arthrobacilins are novel cell growth inhibitors produced by Arthrobactor sp. NR2967. Their structures have been elucidated based on various NMR experiments and acid hydrolysis.