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T Sunazuka

Publications and source records attributed to T Sunazuka.

At least 37 records · Page 2Linked to original sources
PubMed1997

Chemical modification and structure-activity relationships of pyripyropenes. 3. Synthetic conversion of pyridine-pyrone moiety

Structure-activity relationships of the pyridine-pyrone moiety in pyripyropene A (1), a potent acyl-CoA : cholesterol acyltransferase (ACAT) inhibitor of fungal origin, were studied. Several kinds of aromatic or hetero ring substituents for the pyridine moiety were synthesized using unique degradation reaction, following by gamma-acylation. All the six synthesized analogs decreased the inhibitory activity with 20 to 200 times larger IC50 values than that of 1. Furthermore, the pyridine-pyrone substituent also dramatically decrease the inhibitory activity. Thus, the pyridine-pyrone moiety is important for eliciting potent ACAT inhibition.

Journal Article↗
PubMed1996

Chemical modification and structure-activity relationships of pyripyropenes. 1. Modification at the four hydroxyl groups.

Four hydroxyl groups of pyripyropenes have been modified and evaluated for their ability to inhibit microsomal acyl-CoA:cholesterol acyltransferase (ACAT) activity in vitro and to lower cholesterol absorption in vivo in a cholesterol-fed hamster. 7-O-n-Valeryl derivative (8c) improved the in vitro ACAT inhibitory activity (IC50 = 13 nM) about 7 times better than pyripyropene A. Introduction of methanesulfonyl group at 11-hydroxyl group (17a) increased both in vitro activity (IC50 = 19 nM) and in vivo efficacy (ED50 = 10 mg/kg).

Animals↗
PubMed1996

Chemical modification and structure-activity relationships of pyripyropenes. 2. 1,11-Cyclic analogs.

A series of 1,11-cyclic analogs of pyripyropene A were prepared. Replacement of the 1,11-acyl groups of pyripyropenes with 1,11-cyclic acetals effectively improved in vitro acyl CoA:cholesterol acyltransferase (ACAT) inhibitory activity. Especially noteworthy is benzylidene acetal analog 35, the most potent inhibitor (IC50 = 5.6 nM) among the derivatives prepared so far, which showed 16 times more potent inhibitory activity than pyripyropene A.

Animals↗
PubMed1996

Andrastins A-C, new protein farnesyltransferase inhibitors produced by Penicillium sp. FO-3929. II. Structure elucidation and biosynthesis.

The structures of new protein farnesyltransferase inhibitors, andrastins A-C, were elucidated. The cyclopentane ring of andrastins exhibited keto-enol tautomerism, which made the structure hard to elucidate. Therefore, the structure of andrastin A was elucidated by INADEQUATE and 13C-13C couplings using 13C-labeled andrastin A. The absolute configuration of the p-bromobenzoyl derivative of andrastin A was elucidated by X-ray crystallographic analysis and its skeleton was shown to be ent-5 alpha,14 beta-androstane. The biosynthesis of andrastin A was also studied by the incorporation of 13C-labeled acetates. Though the andrastins had a common androstane skeleton, they were biosynthesized from a sesquiterpene and a tetraketide.

Alkyl and Aryl Transferases↗
PubMed1996

Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp. FO-4649. II. Physicochemical properties and structural elucidation.

A new growth inhibitor of IL-6 responsive MH60 cells, chlovalicin (MW; 332, C16H25O5Cl), was found in cultures of Sporothrix sp. FO-4649, together with a known sesquiterpene, ovalicin. The structure of chlovalicin was elucidated by spectroscopic methods. Chlovalicin possesses a chlorinated methylene moiety at the C-1 position, and it corresponds to halogenated products derived from the epoxide ring attached to the C-1 position of ovalicin. The absolute configuration of chlovalicin was clarified as 1S, 2R, 3S, 1'S, 2'R by chemical transformation from ovalicin.

Anti-Bacterial Agents↗
PubMed1996

Arisugacins A and B, novel and selective acetylcholinesterase inhibitors from Penicillium sp. FO-4259. II. Structure elucidation.

The structures of new acetylcholinesterase inhibitors, arisugacins A and B, were elucidated by NMR study. Arisugacins have a (4aR,6aR,12aS,12bS)-4a,6,6a,12,12a, 12b-hexahydro-4a,12a-dihydroxy-4,4,6a,12b-tetramethyl-4H,11H -naphtho[2,1-b] pyrano[3,4-e]pyran-1,11(5H)-dione moiety in common and 3,4-dimethoxyphenyl or 4-methoxyphenyl residues are attached to C-9 of the moiety.

Cholinesterase Inhibitors↗
PubMed1996

Kurasoins A and B, new protein farnesyltransferase inhibitors produced by Paecilomyces sp. FO-3684. II. Structure elucidation and total synthesis.

The structures of new protein farnesyltransferase inhibitors, kurasoins A and B, were elucidated by NMR study. Kurasoins A and B are acyloin compounds having in common a 3-hydroxy-1-phenyl-2-butanone moiety, to which p-hydroxyphenyl and 3-indolyl moieties respectively, are connected at C-4. The structures were confirmed by total synthesis.

Alkyl and Aryl Transferases↗
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase inhibitors: 2-oxetanones with a meta-substituent on the benzene ring in the side chain.

Isosteric side chain analogs of 3a were synthesized and tested for inhibitory activities towards 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase and upon cholesterol production in Hep G2 cells and in mouse liver. It became clear that the lipophilic substituent on the aromatic ring and the terminal hydrophilic group in the side chain were important in the enhancement of activity. 4-[2-(3-n-Hexyloxyphenyl)ethyl]-3-hydroxy-methyl-2-oxetanone (5a) showed equivalent inhibitory activity in vivo to that of 1233A.

Animals↗
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl-CoA synthase inhibitors: 2-oxetanones with a side chain mimicking the extended structure of 1233A.

Structural analogs of 1233A, a microbial metabolite inhibiting 3-hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) synthase, were designed and synthesized. The 2-oxetanone moiety was left intact. All analogs prepared were tested for inhibition of HMG-CoA synthase activity and sterol synthesis in mouse liver and for effect on serum triglyceride levels. Of these analogs, trans-4-[2-[3-(7-carboxy-2- naphthyl)phenyl]ethyl]-3-hydroxymethyl-2-oxetanone (4a) showed the highest inhibitory activity in vitro, and also had in vivo inhibitory activity without causing any increase in triglyceride level.

Animals↗
PubMed1994

Synthesis and biological activity of new 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitors: 2-oxetanones with a side chain mimicking the folded structure of 1233A.

To mimic the folded side chain conformation of 1233A (1), which is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase inhibitor, 1233A analogs with aromatic rings in the side chain were synthesized. The 2-oxetanone moiety was kept intact. Among 1233A and its synthetic analogs, trans-3-hydroxymethyl-4-[2-(7-methoxycarbonyl-1-naphthyl)ethyl]-2-oxe tanone (23) showed the highest HMG-CoA synthase inhibitory activity in vitro. The structure-activity relationship at the side chain is discussed.

Animals↗
PubMed1994

Pyripyropenes, novel inhibitors of acyl-CoA:cholesterol acyltransferase produced by Aspergillus fumigatus. II. Structure elucidation of pyripyropenes A, B, C and D.

The structures of pyripyropenes A, B, C and D, novel acyl-CoA:cholesterol acyltransferase (ACAT) inhibitors, were determined mainly by spectroscopic studies including various NMR measurements. Pyripyropenes have a common structure which consists of pyridine, alpha-pyrone and sesquiterpene moieties. One of the three O-acetyl residues in the sesquiterpene moiety of pyripyropene A is replaced with an O-propionyl residue in pyripyropenes B, C and D.

Aspergillus fumigatus↗