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T Sunazuka

Publications and source records attributed to T Sunazuka.

47 records · Page 3Linked to original sources
PubMed1993

Diolmycins, new anticoccidial agents produced by Streptomyces sp. II. Structure elucidation of diolmycins A1, A2, B1 and B2, and synthesis of diolmycin A1.

The structures of diolmycins A1, A2, B1 and B2, novel anticoccidial agents, were determined by spectroscopic analyses. Diolmycins A1 and A2 are stereoisomers with the structure of 1-(3-indolyl)-4-(p-hydroxyphenyl)-2,3-butanediol. From the chemical synthesis of the erythro-isomer, the relative configurations of diolmycins A1 and A2 were determined to be the erythro- and threo-isomers, respectively. The stereoisomers, diolmycins B1 and B2, were also deduced to be erythro- and threo-1,4-di-(p-hydroxyphenyl)-2,3-butanediol, respectively.

Butylene Glycols↗
PubMed1992

Synthesis of 1233A analogs and their inhibitory activity against hydroxymethylglutaryl coenzyme A synthase.

Simple and efficient syntheses of 1233A analogs were developed and the inhibitory activity of the analogs against hydroxymethylglutaryl coenzyme A (HMG-CoA) synthase was determined. Study of the structure-activity relationships revealed that not only the geometry in beta-lactone moiety but also the length of the carbon side chain is important for inhibitory activity against HMG-CoA synthase.

Animals↗
PubMed1989

Motilides, macrolides with gastrointestinal motor stimulating activity. I. O-substituted and tertiary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal.

Chemical modifications of 8,9-anhydroerythromycin A 6,9-hemiacetal (1), which showed gastrointestinal motor stimulating (GMS) activity 10 times more potent than that of erythromycin A (EM-A), were undertaken to search for derivatives having stronger GMS activity and no antimicrobial activity; details are described in this and a subsequent paper. Displacement of a methyl group of the dimethylamino group of 1 with an ethyl group and an isopropyl group provided de(N-methyl-N-ethyl-8,9-anhydroerythromycin A 6,9-hemiacetal (55) and de(N-methyl)-N-isopropyl-8,9-anhydroerythromycin A 6,9-hemiacetal (58), respectively. They showed significant GMS activity and no antibacterial activity. In particular, the GMS activity of 58 was increased to 248 times that of EM-A. EM-A and the derivatives obtained in this study mimic exogenous motilin in the dog. The name "motilide", meaning a motilin-like macrolide, is proposed for this new family of macrolide compounds.

Anti-Bacterial Agents↗
PubMed1989

Motilides, macrolides with gastrointestinal motor stimulating activity. II. Quaternary N-substituted derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal and 9,9-dihydroerythromycin A 6,9-epoxide.

A series of quaternary ammonium derivatives of 8,9-anhydroerythromycin A 6,9-hemiacetal (1) and 9,9-dihydroerythromycin A 6,9-epoxide (2) has been prepared and tested for antimicrobial activity and gastrointestinal motor stimulating (GMS) activity in the dog (in vivo). The GMS activity is enhanced markedly when small alkyl halides and unsaturated alkyl halides such as allyl bromide and propargyl bromide are added to the dimethylamino group of 1. Among them, N-propargyl-8,9-anhydroerythromycin A 6,9-hemiacetal bromide (3) exhibits GMS activity 2890 times stronger than that of erythromycin A and is completely devoid of antimicrobial activity. The potency of 3 is comparable to that of synthetic motilin both in vitro and in vivo.

Animals↗
PubMed1986

Antagonistic interactions of macrolides and synergimycins on bacterial ribosomes.

The affinity of ribosomes for VS (virginiamycin S, a type B synergimycin) is known to be increased by VM (virginiamycin M, a type A synergimycin). Erythromycin, a macrolide, displaces ribosome-bound VS in the absence of VM, but is ineffective in its presence. In the present work, the ability of spiramycin and tylosin (macrolide subgroups) derivatives to displace ribosome-bound VS, in the presence and in the absence of VM, has been explored. All macrolides with in-vitro activity displaced ribosome-bound VS: the displacement curves produced by tylosin and spiramycin derivatives virtually overlapped. When VM was added to these systems, displaced VS became readily attached to ribosomes in the case of erythromycin, did not bind appreciably within 20 min incubation in the presence of tylosin, and underwent a slow binding in the case of an N-substituted tylosin. The 16-membered macrolides (leucomycin, spiramycin and tylosin subgroups) can therefore be distinguished from the 14-membered macrolides (erythromycin subgroup) by the antagonistic effect displayed toward VM.

Bacteria↗
PubMed1985

Structure activity relationships of spiramycins.

Sixty-six derivatives of spiramycin I and neospiramycin I were synthesized and evaluated by four parameters, MIC, affinity to ribosomes (ID50), therapeutic effect in mice and retention time in HPLC. Among the derivatives, 3,3'',4''-tri-O-propionyl- and 3,4''-di-O-acetyl-3''-O-butyrylspiramycin I showed the highest therapeutic effect which was superior to acetylspiramycin. Structure activity relationships of spiramycins are discussed.

Animals↗
PubMed1985

Chemical modification of spiramycins. VI. Synthesis and antibacterial activities of 3,3''-di-O-acyl-4''-O-sulfonyl and 3,3''-di-O-acyl-4''-O-alkyl derivatives of spiramycin I.

3,3''-Di-O-acyl-4''-O-sulfonyl and 3,3''-di-O-acyl-4''-O-alkyl derivatives of spiramycin I were synthesized and evaluated by four parameters, antibacterial activity, affinity to ribosomes, lypophilicity and therapeutic effects. Among them, 3,3''-di-O-acetyl-4''-O-mesyl and 3,3''-di-O-acetyl-4''-O-methylspiramycin I having relatively small substituents at 4''-position were the most effective in mouse protection tests, and the results were comparable to acetylspiramycin.

Animals↗
PubMed1984

Chemical modification of spiramycins. III. Synthesis and antibacterial activities of 4''-sulfonates and 4''-alkylethers of spiramycin I.

Among the derivatives protected with t-butyldimethylsilylether of spiramycin I, 2'-O-acetylspiramycin I 3,18-(O-t-butyldimethylsilyl)acetal was found to be a suitable intermediate for 4''-modification of spiramycin I. Seven 4''-sulfonates and four 4''-alkylethers were synthesized, which were more active against bacteria in vitro than spiramycin I. 4''-Substituted derivatives with relatively small sulfonyl and alkyl groups were comparable in therapeutic effect to spiramycin I.

Animals↗
PubMed1984

Chemical modification of spiramycins. IV. Synthesis and in vitro and in vivo activities of 3'',4''-diacylates and 3,3'',4''-triacylates of spriamycin I.

3'',4''-Diacylates and 3,3'',4''-triacylates of spiramycin I were synthesized and evaluated by the four parameters, MIC against bacteria, affinity to ribosomes, retention time in HPLC and therapeutic effect. Among them, 3,3'',4''-tri-O-propionyl and 3,4''-di-O-acetyl-3''-O-butyryl-spiramycin I were the most active in vivo, which were superior to acetylspiramycin.

Animals↗