Setsuo Harada

A new anti-MRSA dipeptide, TAN-1057 A

Abstract The chemical structure of a new dipeptide antibiotic, TAN-1057 A, isolated from the broth filtrate of Flexibacter sp. PK-74 was determined to be (3′S, 5S)-5-[N-methyl-N-(3′-amino-6′-guanidinohexanoyl)amino]5,6-dihydro-2-ureido-4(1H)-pyrimidone. The antibiotic was specifically active against staphylococcus species including methicillin-resistant strains.

Structure of lactivicin, an antibiotic having a new nucleus and similar biological activities to β-lactam antibiotics

Abstract The structure of a new antibiotic, lactivicin, was determined to be [4S]-2-(4-acetylamino-3-oxo-2-isoxazolidinyl)-5-oxo-tetrahydrofuran-2-carboxylic acid.

Chemistry of a new antibiotic: lactivicin

Abstract A novel antibiotic, lactivicin (LTV), was isolated from the culture filtrates of two bacterial strains by various types of chromatography. LTV exists in aqueous solution as an equilibrium mixture of two epimers in a ratio of about 1:1. The chemical structure of LTV (C 10 H 12 N 2 O 7 ) was determined to be 2-(4S-acetylamino-3-oxo-2-isoxazolidinyl)-5-oxo-tetrahydrofuran-2-carboxylic acid. The absolute configuration at the C-6 position was elucidated from the CD spectral data and X-ray crystallographic analysis of 4-amino-lactivinic acid obtained by the iminoether method. This compound is useful as a starting material for chemical modification. LTV showed antibacterial activity against Gram-positive and negative bacteria, susceptibility to β-lactamases, and affinity for penicillin-binding proteins. We therefore concluded that LTV is a novel skeleton antibiotic having β-lactam-like activities.

A novel amino acid antibiotic tan-950

Abstract A novel antifungal antibiotic, TAN-950 A, was isolated from the culture filtrate of Streptomyces platensis A-136. Its structure was determined to be (S)-2-amino-3-(isoxazolin-5-on-4-yl)-propanoic acid. Minor components, TAN-950 B, C, D and E, were found to be present in an equilibrium mixture containing TAN-950 A. Their structures were determined from spectral analyses. X-ray crystallographic analysis and synthesis from L-glutamic acid.

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

STRUCTURE DETERMINATION OF INDOLOCARBAZOLE ALKALOIDS BY NMR SPECTROSCOPY

Abstract The structures of two indolocarbazole alkaloids with macrophage-activating properties, TAN-1030 A and TAN-999, were determined based on NMR spectral analysis.

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.

A novel glutamate agonist, TAN-950 A, isolated from streptomycetes.

A novel antifungal amino acid antibiotic, TAN-950 A ([S]-2-amino-3-(2,5-dihydro-5-oxo-4-isoxazolyl)propanoic acid), was found to have affinity for three excitatory amino acid (EAA) receptors and to inhibit [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), [3H]kainate and [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP) binding competitively. It caused excitation of rat hippocampal CA1 neurons in vitro, an effect that was antagonized by an AMPA/kainate antagonist, 6,7-dinitroquinoxaline-2,3-dione (DNQX). Chemical modification of TAN-950 A brought about a large change in its pharmacological activity. Alkylation at the C-3 position of the isoxazolone ring markedly increased the ability to elicite neuronal firing. This agonistic effect was also antagonized by DNQX. The (R) enantiomer of TAN-950 A had increased selectivity for the N-methyl-D-aspartate (NMDA) receptor subtype. This selectivity was further enhanced by removal of the methylene group from the amino acid moiety. The most potent NMDA agonistic activity was observed with [R]-2-amino-2-(2,5-dihydro-3-methyl-5-oxo-4-isoxazolyl)acetic acid. These derivatives of TAN-950 A might be useful agents for investigating the pharmacological and physiological roles of EAA receptors.

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.

Two sulfur-containing ansamycin antibiotics fromStreptomyces albolongus

Two sulfur-containing ansamycin antibiotics were isolated from the culture broth ofStreptomyces albolongus C-46366; the major one was identical with awamycin and the minor one was a new ansamycin antibiotic, ansathiazin. Their structures were elucidated from their reactions and spectroscopic analyses. These antibiotics were active against gram-positive bacteria, acid-fast bacteria and a protozoan.