Kazuo Iguchi

Clavulones, new type of prostanoids from the stolonifer clavularia viridis quoy and gaimard

Abstract Three new prostanoids, clavulone I( 1 ), II( 2 ) and III( 3 ), were isolated from the Japanese Stolonifer Claularia viridis Quoy and Gaimard. The structures of these prostanoids were determined on the basis of spectral data and chemical reactions.

Chlorovulones, new halogenated marine prostanoids with an antitumor activity from the stolonifer clavularia viridis Quoy and Gaimard

Abstract New halogenated marine prostanoids, chlorovulone I, II and III were isolated from the stolonifer Clavularia viridis Quoy and Gaimard. The structure elucidation and the antitumor activity of chlorovulones were described.

Absolute stereochemistry of new prostanoids clavulone I, II and III, from Clavularia viridis Quoy and Gaimard

Abstract Absolute configurations at the C-4 and -12 positions of a new type of prostanoids clavulone I ( 1 ), II ( 2 ) and III ( 3 ), isolated from Clavularia viridis Quoy and Gaimard, have been elucidated on the basis of chemical and spectral evidence.

Strongylodiols A, B and C, new cytotoxic acetylenic alcohols isolated from the Okinawan marine sponge of the genus Strongylophora as each enantiomeric mixture with a different ratio

Three new cytotoxic long-chain acetylenic alcohols, strongylodiols A, B and C, were isolated from the Okinawan marine sponge of the genus Strongylophora. Their gross structures were elucidated based on spectroscopic analysis. During the process for determination of the absolute stereochemistry at C-6 using the modified Moshers method, these acetylenic alcohols were each found to be an enantiomeric mixture with a different ratio; 91:9 for strongylodiol A, 97:3 for strongylodiol B and 84:16 for strongylodiol C. The R configuration for each major enantiomer was established by the modified Moshers method. Each enantiomer was separated and fully characterized.

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

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.

Hydroxylation of various molecules including heterocyclic aromatics using recombinant Escherichia coli cells expressing modified biphenyl dioxygenase genes

Abstract Various molecules, in which heterocyclic aromatics are linked with phenyl or benzyl groups, were converted to their corresponding cis -dihydrodiols by recombinant Escherichia coli cells expressing modified biphenyl dioxygenase genes. Heterocyclic aromatic compounds with substituted phenyl or aliphatic moieties were also biotransformed to the hydroxylated products by the cells. Many of the converted products were novel compounds. These compounds are potentially useful as versatile starting materials for the chemical synthesis of pharmaceuticals and biologically active organic molecules.

Determination of absolute configuration of chlorovulones by cd measurement and by enantioselective synthesis of (−)-chlorovulone II1

Abstract Absolute configuration of chlorovulones, new halogenated marine prostanoids with an antitumor activity isolated from the stolonifer Clavularia viridis Quoy and Gaimard, has been established on the basis of the CD measurement of the chlorovulone derivatives and of the enantioselective synthesis of (−)-chlorovulone II.

Aragusterols E-H, new 26,27-cyclosterols from the Okinawan marine sponge of the genus Xestospongia and absolute configurations of xestokerols A and B

Abstract New 26, 27-cyclosterols, aragusterols E-H, were isolated from the Okinawan marine sponge of the genus Xestospongia . Their structures were determined by spectroscopic measurement and chemical conversion. The absolute configurations of xestokerols A and B were determined by chemical conversion.

Mechanism of action of aragusterol a (YTA0040), a potent anti-tumor marine steroid targeting the G1 phase of the cell cycle

Aragusterol A (YTA0040), isolated from the Okinawan marine sponge of the genus Xestospongia, is a potent anti‐tumor marine steroid that possesses a unique structural component. This compound showed broad‐spectrum anti‐proliferative activity against a panel of 14 human cancer cell lines (IC50 = 0.01–1.6 μM). P‐glycoprotein–mediated, multidrug‐resistant cells showed cross‐resistance to YTA0040 cells, whereas cisplatin‐resistant non‐small‐cell lung‐cancer (NSCLC) sublines showed a collateral sensitivity to YTA0040. In transplantable murine tumor models, YTA0040 displayed a broad spectrum and high degree of anti‐tumor activity when administered i.p. or p.o. (life span T/C = 135–234%). In P388 murine leukemia cells, YTA0040 caused dose‐ and time‐dependent suppression of nucleic acid and protein synthesis, with protein synthesis being more potently and rapidly inhibited than nucleic acid synthesis. Flow‐cytometric analysis revealed that YTA0040 blocked the entry of human NSCLC‐derived A549 cells into S phase, leading to arrest in the G1 phase of the cell cycle. Western blot analysis demonstrated that YTA0040 caused a dose‐dependent decrease in the levels of expression of hyperphosphorylated pRb and cyclin A in A549 cells. The level of p53 protein expression was decreased by YTA0040 treatment. A higher concentration of YTA0040 down‐regulated the levels of expression of CDK2, CDK4, cyclin D1 and cyclin E. These findings indicated that YTA0040 arrested human NSCLC cells in late G1 phase of the cell cycle through inhibition of pRb phosphorylation. Inhibition of pRb phosphorylation by YTA0040 resulted from down‐regulation of levels of expression of the CDKs and cyclins involved in the G1/S transition and not from induction of p53 and/or the CDK inhibitor p21. Int. J. Cancer 88:810–819, 2000.

Reductive coupling of allylic halides by chlorotris(triphenylphosphine)cobalt(I)

Abstract Reactions of geranyl and farnesyl halide, and their geometrical isomers with chlorotris(triphenylphosphine)cobalt(I) gave the corresponding geometrically pure coupling products under mild and non-basic conditions. Squalenes were stereospecifically synthesized by this method.