Publications by authors named "Kazuo Iguchi"

24 Publications

  • Page 1 of 1

Isolation and identification of a potent antimalarial and antibacterial polyacetylene from Bidens pilosa.

Planta Med 2009 May 4;75(6):624-8. Epub 2009 Mar 4.

Showa Pharmaceutical University, Higashi-tamagawagakuen, Machida, Tokyo 194-8543, Japan.

Diseases caused by malaria parasites and pathogenic bacteria were thought to be on the brink of eradication in the 1950-1960s, but they have once again become a serious threat to mankind as a result of the appearance of multidrug resistant strains. The spread of these multidrug resistant organisms has prompted a worldwide search for new classes of effective antimalarial and antibacterial drugs. Natural products have been recognized as highly important candidates for this purpose. Our attention has focused on the herbal plant Bidens pilosa, a weed common throughout the world, as one of the target plants in the search for new active compounds, owing to its empirical use in the treatment of infectious diseases and to pharmaco-chemical studies of its crude extract. We report the isolation of two new compounds of B. pilosa, the linear polyacetylenic diol 1 and its glucoside 2 which have previously been isolated from different plants. Compound 1 exhibited highly potent antimalarial and antibacterial properties in vitro as well as potent antimalarial activity by way of intravenous injection in vivo, thereby representing a promising new class of drugs potentially effective in the treatment of malarial and bacterial diseases. We suspect that discovery of these compounds in B. pilosa in appreciable quantity is because the Fijian tradition of using the fresh plant for extraction rather than the Asian tradition of using dried plants (1 is unstable in the dried state) was followed.
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http://dx.doi.org/10.1055/s-0029-1185377DOI Listing
May 2009

Toward the synthesis of didemnaketal B: a convergent synthesis of the C9-C28 subunit.

Org Lett 2008 Sep 24;10(17):3873-6. Epub 2008 Jul 24.

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Synthesis of the C9-C28 subunit of didemnaketal B has been developed. This subunit was convergently prepared from four chiral synthons and at the longest linear sequence required 16 steps.
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http://dx.doi.org/10.1021/ol801395qDOI Listing
September 2008

Structure of an unsaturated fatty acid with unique vicinal dimethyl branches isolated from the Okinawan soft coral of the genus Sinularia.

Chem Pharm Bull (Tokyo) 2008 Jun;56(6):861-3

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.

A new unsaturated fatty acid with unique vicinal dimethyl branches was isolated from the Okinawan soft coral of the genus Sinularia. The structure of the compound was determined based on the results of spectroscopic analysis and chemical conversion. The absolute configuration was deduced by applying the Ohrui-Akasaka method.
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http://dx.doi.org/10.1248/cpb.56.861DOI Listing
June 2008

Brianodins A-D, briarane-type diterpenoids from soft coral Pachyclavularia sp.

J Nat Prod 2008 Apr 18;71(4):633-6. Epub 2008 Mar 18.

Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.

Four new briarane-type diterpenoids, brianodins A-D ( 1- 4), were isolated from a soft coral, Pachyclavularia sp., and the structures and relative stereochemistry of 1- 4 were elucidated on the basis of spectroscopic data. The absolute configurations of 3 and 4 were assigned by the MTPA method. Brianodin A ( 1) showed a modest cytotoxicity.
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http://dx.doi.org/10.1021/np070684pDOI Listing
April 2008

Marine diterpenoids with a briarane skeleton from the Okinawan soft coral Pachyclavularia violacea.

Chem Pharm Bull (Tokyo) 2007 Dec;55(12):1671-6

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Five new briarane-type diterpenoids, pachyclavulides E (5), F (6), G (7), H (8) and I (9), were isolated from the Okinawan soft coral Pachyclavularia violacea. The structures of these compounds were elucidated based on the results of spectroscopic analysis. Compound 5 showed a weak growth-inhibitory activity in vitro toward cancer cells.
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http://dx.doi.org/10.1248/cpb.55.1671DOI Listing
December 2007

Nine acetylenic alcohols isolated from the Okinawan marine sponge of the genus Petrosia (Strongylophora).

Nat Prod Res 2007 Jul;21(8):710-20

School of Life Sciences, Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, Japan.

Nine new acetylenic alcohols 1-9 were isolated from a marine sponge belonging to the genus Petrosia (Strongylophora). The structures were elucidated mainly based on the analysis of one-and two-dimensional NMR spectral data. To determine the position of the central double bonds in 1-8, each compound was cleaved with OsO(4) and HIO(4), and the resulting aldehyde was converted to the corresponding 2,4-dinitrophenylhydrazone. Analysis of the high-resolution mass and (13)C NMR spectral data of each 2,4-dinitrophenylhydrazone clarified the position of the central double bonds in 1-8.
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http://dx.doi.org/10.1080/14786410600906525DOI Listing
July 2007

Structure of cymbidine A, a monomeric peptidoglycan-related compound with hypotensive and diuretic activities, isolated from a higher plant, Cymbidium goeringii (Orchidaceae).

Chem Pharm Bull (Tokyo) 2007 May;55(5):780-3

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan .

The structure of a new monomeric peptidoglycan-related compound with hypotensive and diuretic activities, cymbidine A (1) isolated from the orchid Cymbidium goeringii, was elucidated mainly by spectroscopic analysis. The structure of 1 was shown to involve four amino acids (D-alanin, meso-diaminopimelic acid, D-gultamic acid, and L-valine) and two amino sugars (N-acetylglucosamine and 1,6-anhydro-N-acetylmuramic acid). The sequence of the amino acids and amino sugars was determined by the analysis of 2D NMR data. The absolute stereochemistries of the three amino acids (D-Ala, D-Glu and L-Val) were determined by the modified Marfey's method, and the (6S,10R) configurations of meso-diaminopimelic acid in 1 were indicated on the basis of the CD analysis. The absolute stereochemistry of 1,6-anhydro-N-acetylmuramic acid was also determined by CD data.
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http://dx.doi.org/10.1248/cpb.55.780DOI Listing
May 2007

Total synthesis of (+/-)-clavubicyclone.

Org Lett 2006 Oct;8(21):4883-5

School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

[reaction: see text] The total synthesis of racemic clavubicyclone (1), which was isolated from Okinawan soft coral by our group, is described. The bicyclo[3.2.1]octane skeleton was prepared by Cope rearrangement of a divinylcyclopropane derivative. Three functional groups on the skeleton were constructed by Barton decarboxylation, Wittig reaction, and alkylation.
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http://dx.doi.org/10.1021/ol061947uDOI Listing
October 2006

Briarane-type diterpenoids from the Okinawan soft coral Pachyclavularia violacea.

J Nat Prod 2006 Jan;69(1):2-6

School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Four new briarane-type diterpenoids, pachyclavulides A (1), B (2), C (3), and D (4), were isolated from the Okinawan soft coral Pachyclavularia violacea. The structures of these compounds were elucidated on the basis of the results of spectroscopic analysis. The absolute configuration of pachyclavulide A (1) was determined by the X-ray crystallographic analysis of its p-bromobenzoyl ester.
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http://dx.doi.org/10.1021/np0580661DOI Listing
January 2006

Solid-phase synthesis and biological activity of a combinatorial cross-conjugated dienone library.

Chemistry 2006 Feb;12(5):1368-76

Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan.

The solid-phase synthesis of a combinatorial cross-conjugated dienone library based on the structure of clavulones and their biological activity are reported. Clavulones are a family of marine prostanoids, and are composed of a cross-conjugated dienone system bearing two alkyl side-chains. The cross-conjugated dienone system irreversibly reacted with two nucleophiles. Our strategy for the solid-phase synthesis of the cross-conjugated dienones involves the Sonogashira-coupling reaction of a solid-supported cyclopentenone 10 bearing an acetylene group, followed by aldol condensation with aldehydes. The diphenyl derivative 7 aA was prepared from the solid-supported cyclopentenone 10 in 56% total yield. Combinatorial synthesis of a small library using twelve halides and eight aldehydes resulted in the production of 74 desired compounds from 98 candidates, and were detected by their mass spectra. Antiproliferative effects of the crude compounds against HeLaS3 cells showed that eleven samples showed strong antitumor activity (IC50<0.05 microM). Further biological examination of four purified compounds by using five tumor cell lines (A549, HeLaS3, MCF7, TMF1, and P388) revealed strong cytotoxicity comparable to that of adriamycin.
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http://dx.doi.org/10.1002/chem.200500793DOI Listing
February 2006

Acetylenic strongylodiols from a Petrosia (Strongylophora) Okinawan marine sponge.

J Nat Prod 2005 Jul;68(7):1001-5

School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Seven new long-chain acetylenic alcohols, strongylodiols D-J, were isolated from an Okinawan marine sponge of the genus Petrosia (Strongylophora). The structures of these compounds were elucidated on the basis of the results of spectroscopic analysis and chemical reaction. Analysis of the MNA esters of the acetylenic alcohols disclosed that these compounds were each an enantiomeric mixture in a different ratio.
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http://dx.doi.org/10.1021/np040233uDOI Listing
July 2005

Stolonilactone, a novel terpenoid-related compound, isolated from the Okinawan soft coral Clavularia koellikeri.

J Org Chem 2004 Jun;69(13):4351-5

School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

A novel terpenoid-related compound, stolonilactone (1), was isolated from the Okinawan soft coral Clavularia koellikeri. The structure of 1 was elucidated on the basis of spectroscopic analysis. A possible biogenesis of 1 through the [4 + 2]-cycloaddition of a trisnorsesquiterpenoid-type diene and a cembranolide-type dienophile is proposed.
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http://dx.doi.org/10.1021/jo030335+DOI Listing
June 2004

New marine sesquiterpenoids and diterpenoids from the Okinawan soft coral Clavularia koellikeri.

J Nat Prod 2004 Apr;67(4):577-83

Laboratory of Bioorganic Chemistry, School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Six new terpenoids (two maaliane-type sesquiterpenoids, 1 and 2, one aromadendrane-type sesquiterpenoid, 3, one noraromadendrane-type sesquiterpenoid, 4, and two neodolabellane-type diterpenoids, 5 and 6) were isolated from the Okinawan soft coral Clavularia koellikeri. The structures of these compounds were determined on the basis of the results of spectroscopic analysis, chemical conversion, and X-ray crystallographic analysis. Compound 6 exhibited modest growth-inhibition effect in vitro toward tumor cells.
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http://dx.doi.org/10.1021/np0304013DOI Listing
April 2004

Enantioselective total synthesis of (+)-tricycloclavulone.

J Am Chem Soc 2004 Apr;126(14):4520-1

School of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

The first total synthesis of (+)-tricycloclavulone having a unique tricyclo[5,3,0,01,4]decane skeleton and six chiral centers was achieved in a highly stereoselective manner. It includes a catalytic enantioselective [2+2]-cycloaddition reaction using novel chiral copper catalyst, extremely effecting an intramolecular ester transfer reaction, and asymmetric reduction of the carbonyl group on the alpha-chain using Noyori's chiral ruthenium catalyst.
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http://dx.doi.org/10.1021/ja049750pDOI Listing
April 2004

Efficient solid-phase synthesis of clavulones via sequential coupling of alpha- and omega-chains.

Org Lett 2004 Apr;6(7):1103-6

Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan.

We describe an efficient solid-phase synthesis of clavulones via the sequential coupling of the alpha- and omega-chains, involving two separate carbon-carbon bond-forming steps. The tetrahydropyranyl linker survived these reaction conditions and was cleaved without decomposing the unstable cross-conjugated dienones. Our methodology has allowed us to prepare six clavulone derivatives that are varied within the alpha-chain.
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http://dx.doi.org/10.1021/ol036361bDOI Listing
April 2004

Effective irreversible alkylating reagents based on the structure of clavulones.

Bioorg Med Chem Lett 2004 Feb;14(4):837-40

Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, 2-12-1 Ookayama, Meguro, Tokyo 152-8552, Japan.

We describe the design and synthesis of alkylating reagents based on the structure of clavulones. They are composed of cross-conjugated dienone system and irreversibly reacted with two nucleophiles under mildly basic conditions via beta-elimination. Hydroxyl derivative 7b showed the highest reactivity toward thiols and showed the strongest cytotoxicity in Hela S3 cells among the three derivatives having a different protecting group at the tert-hydroxyl group.
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http://dx.doi.org/10.1016/j.bmcl.2003.12.026DOI Listing
February 2004

Molecular phylogenetic relationships between prostanoid-containing Okinawan soft coral ( Clavularia viridis) and nonprostanoid-containing Clavularia species based on ribosomal ITS sequence.

Mar Biotechnol (NY) 2003 Jul-Aug;5(4):401-7

School of Life Science, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan.

To study phylogenetic relationships among Okinawan soft corals of the genus Clavularia, the ribosomal internal transcribed spacer sequences of host corals and the 18S rDNA sequences of symbiotic algae were analyzed. The molecular phylogenetic trees of hosts showed that a prostanoid-containing species, Clavularia viridis, is deeply diverged from other species of Clavularia which do not biosynthesize the prostanoids as the main secondary metabolites. Comparison of their trees suggested poor phylogenetic concordance between hosts and symbionts.
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http://dx.doi.org/10.1007/s10126-002-0084-zDOI Listing
March 2004

Isolation and structures of new halogenated prostanoids from the Okinawan soft coral Clavularia viridis.

J Nat Prod 2003 Nov;66(11):1434-40

School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Fifteen new halogenated prostanoids 9-23 were isolated as minor constituents from the Okinawan soft coral Clavularia viridis. Compounds 9-11 were new members of iodovulone, and compounds 12-18 were 12-O-acetyliodovulones, 12-O-acetylbromovulones, and 12-O-acetylchlorovulones. Compounds 19-23 were 10,11-epoxy congeners of iodovulone, bromovulone, and chlorovulone. The structures of these compounds were determined on the basis of spectroscopic analysis and chemical conversion.
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http://dx.doi.org/10.1021/np030181tDOI Listing
November 2003

Localization of clavulones, prostanoids with antitumor activity, within the Okinawan soft coral Clavularia viridis (Alcyonacea, Clavulariidae): preparation of a high-purity Symbiodinium fraction using a protease and a detergent.

Lipids 2003 Sep;38(9):991-7

Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan.

To investigate the localization of clavulones (CV), prostanoids with antitumor activity, in the Okinawan soft coral Clavularia viridis, we developed a method for the isolation of Symbiodinium cells from the coral, i.e., treatment of a coral homogenate with a protease, pronase E, and a detergent, Nonidet P-40. The conditions for the treatment were optimized by monitoring the morphology microscopically and the amount of chlorophyll in the Symbiodinium fraction (SymF) optically. To evaluate the purity of SymF and a Symbiodinium-free coral fraction (CorF), we analyzed them for proteins and lipids using cultivated Symbiodinium as a reference. TLC of lipids revealed that SymF contained a greater amount of glycolipids, whereas CorF comprised mostly phospholipids. SDS-PAGE of proteins in SymF and CorF revealed their distinct profiles. Thus, we could obtain each fraction with high purity; we reached the conclusion that CV and arachidonic acid, their possible precursor, are localized exclusively in the insoluble fraction of host coral cells.
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http://dx.doi.org/10.1007/s11745-003-1153-2DOI Listing
September 2003

Isolation of three marine prostanoids, possible biosynthetic intermediates for clavulones, from the Okinawan soft coral Clavularia viridis.

Chem Pharm Bull (Tokyo) 2003 Aug;51(8):909-13

School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-0392, Japan.

Three marine prostanoids, 1, 2, and 3, were isolated from the extract of the Okinawan soft coral Clavularia viridis. The structures of these compounds were assigned based on the results of spectroscopic analysis. Compound 1 was shown to be preclavulone-A methyl ester, and this is the first isolation of the ester of preclavulone-A as a natural product. Preclavulone-A is proposed to be the key intermediate in the biosynthesis of marine prostanoids exemplified by clavulones in C. viridis. The new prostanoid 3 was suggested to be a biosynthetic intermediate from preclavulone-A to clavulones, and a possible biogenetic pathway via 3 is proposed.
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http://dx.doi.org/10.1248/cpb.51.909DOI Listing
August 2003

Isolation of peridinin-related norcarotenoids with cell growth-inhibitory activity from the cultured dinoflagellate of Symbiodinium sp., a symbiont of the Okinawan soft coral Clavularia viridis, and analysis of fatty acids of the dinoflagellate.

Chem Pharm Bull (Tokyo) 2003 Jun;51(6):724-7

School of Life Science, Tokyo University of Pharmacy and Life Science, Tokyo, Japan.

Two norcarotenoids, 1 and 2, related to peridinin (3) were isolated from the cultured dinoflagellate of the genus Symbiodinium, a symbiont of the Okinawan soft coral Clavularia viridis, which contains in abundance antitumor marine prostanoids such as clavulones. The structures of 1 and 2 were elucidated on the basis of spectroscopic analysis. These compounds showed significant growth-inhibitory activity in vitro toward cancer cells. Analysis of fatty acids of the dinoflagellate was also carried out, suggesting that the marine prostanoids are produced by the host soft coral itself.
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http://dx.doi.org/10.1248/cpb.51.724DOI Listing
June 2003

New marine diterpenoids from the Okinawan soft coral Clavularia koellikeri.

J Nat Prod 2002 Oct;65(10):1441-6

Laboratory of Bioorganic Chemistry, School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Japan.

Chemical investigation of the Okinawan soft coral Clavularia koellikeri resulted in the isolation of two new cembrane diterpenoids (1 and 2) and one new dollabelane diterpenoid, 3. Their structures were determined on the basis of the results of spectroscopic analysis. Compounds 1 and 3 were examined for in vitro growth-inhibition effects toward tumor cells.
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http://dx.doi.org/10.1021/np0200156DOI Listing
October 2002

New biologically active marine sesquiterpenoid and steroid from the okinawan sponge of the genus Axinyssa.

Chem Pharm Bull (Tokyo) 2002 Sep;50(9):1286-9

School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.

A new bisabolane-type sesquiterpenoid, (E)-3-isocyanobisabolane-7,10-diene (1), and a new epidioxyergostane-type steroid, 9(11)-dehydroaxinysterol (2), were isolated from the Okinawan sponge of the genus Axinyssa. Their structures were elucidated based on the results of spectroscopic analysis and chemical conversion. Epidioxysterol 2 was found to show significant growth inhibitory effects against human cancer cell lines.
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http://dx.doi.org/10.1248/cpb.50.1286DOI Listing
September 2002

Tricycloclavulone and clavubicyclone, novel prostanoid-related marine oxylipins, isolated from the Okinawan soft coral Clavularia viridis.

J Org Chem 2002 May;67(9):2977-81

School of Life Science, Tokyo University of Pharmacy and Life Science, Horinouchi, Hachioji, Tokyo 192-03, Japan.

Two novel prostanoid-related marine oxylipins, tricycloclavulone (1) and clavubicyclone (2), were isolated from the Okinawan soft coral Clavularia viridis. The structures of 1, having a tricyclo[5.3.0.0(1,4)]decane ring system, and 2, having a bicyclo[3.2.1]octane ring system, were elucidated on the basis of spectroscopic analysis. Clavubicyclone showed a moderate growth inhibition activity against tumor cells in vitro.
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http://dx.doi.org/10.1021/jo011043gDOI Listing
May 2002
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