Published papers

Auriculol, a cytotoxic oxygenated squalene, was isolated from the Japanese sea hare Dolabella auricularia, and its stereostructure was elucidated by spectral analysis and organic synthesis.

Novel imidazole compounds, catharsitoxins A, B, C, D, E and F, were isolated from the Chinese remedy qiung laug. Their structures were determined by 2D NMR. To confirm their structures and to ensure an adequate supply for further biological studies, catharsitoxins A and D were synthesized.

Four new monochlorinated diterpene alkaloids, haterumaimides F-I (1-4), and two known ones, dichlorolissoclimide and chlorolissoclimide, were isolated from an ascidian Lissoclinum sp. Their structures with absolute stereochemistries were elucidated by chemical and spectral analyses. Haterumaimides F-I (1-4) inhibited the first cleavage of fertilized sea urchin eggs and exhibited potent to weak cytotoxicities against P388 cells.

Hedathiosulfonic acids A and B were isolated from the deep-sea urchin Echinocardium cordatum, and were determined to be novel 6-undecanethiosulfonic acids by 2D NMR, HRMS, and methylation reaction. Hedathiosulfonic acids exhibited acute toxicity.

Zamamistatin was isolated from the Okinawan sponge Pseudoceratina purpurea. It was determined to be a novel bromotyrosine derivative by careful analysis of 2D NMR spectra and comparison of its 1H NMR spectrum with those of structurally related compounds. The absolute stereostructure of zamamistatin was determined by the modified Mosher's method. Zamamistatin exhibited significant antibacterial activity against Rhodospirillum salexigens, which has adhering properties.

New bisnorditerpenes, hedaols A (1), B (2), and C (3), were isolated from the Japanese brown alga Sargassum sp. Their structures were determined by spectroscopic analysis. The absolute stereocenter of 1 was determined by the modified Mosher's method. Hedaols showed low cytotoxicity against P388 cells.

Pteriatoxins A, B and C, extremely potent toxins, were isolated from the Okinawan bivalve Pteria penguin. Their structures were determined based on NMR and MS/MS spectral analyses. Pteriatoxins have polyether macrocycles composed of 6,7-spiro, 5,6-bicyclo and 6,5,6-trispiro ketal rings, the same as in pinnatoxins.

Pinnatoxins B and C, the most toxic components in the pinnatoxin series, were successfully purified from the Okinawan bivalve Pinna muricata. Their gross structures were determined based on NMR and MS/MS spectral analyses. Their stereostructures were mainly determined by transformation reactions. Pinnatoxins B and C, C-34 epimers of each other, have an amphoteric macrocycle composed of 6,7-spiro, 5,6-bicyclo and 6,5,6-trispiro ketal rings, the same as in pinnatoxins A and D.

Cytotoxic endoperoxides, haterumadioxins A (1) and B (2), were isolated from the Okinawan sponge Plakortis lita. Their structures were determined by spectroscopic analysis. The absolute stereostructure of 1 was determined by degradation reactions and the modified Mosher's method. Haterumadioxins showed significant cytotoxicity against 38 human cancer cell lines.

Two new sesterterpenic acids, which exhibited moderate cytotoxicity, were isolated from the marine sponge Ircinia sp. Their absolute stereochemistries were determined by spectroscopic and chemical analyses. Their configurations at C15 were different from those of previously isolated sesterterpenes. This result suggests the existence of a (14Z)-geranylfarnesyl pyrophosphate, which is yet unknown in nature.

(Matrix presented) Enantioselective synthesis of attenols A and B was accomplished by using diastereoselective hydroboration, Lindlar reduction, and acid-catalyzed acetal formation.

Five new dichlorolissoclimide-type diterpenoids, haterumaimides A-E, were isolated from an ascidian, Lissoclinum sp., and the absolute stereostructures of haterumaimides A-D and the relative stereostructure of haterumaimide E were determined by spectroscopic and chemical analyses. Haterumaimides A-E inhibited the first cleavage of fertilized sea urchin eggs and exhibited cytotoxicity against P388 cells.

Two new lipopeptides, amamistatins A and B, were isolated from Nocardia asteroides SCRC-A2359, and their absolute stereostructures were determined by spectroscopic and chemical analyses. Amamistatin A inhibited the growth of human rumor cell lines. (C) 2000 Elsevier Science Ltd.

Pinnamine, a novel marine alkaloid, was isolated from the Okinawan bivalve Pinna muricata. Pinnamine was determined to be an alkaloid containing a dihydropyrone ring by spectroscopic analysis. The relative stereostructure of pinnamine was determined by an analysis of coupling constants and NOE experiments; the absolute stereostructure was determined by an analysis of the circular dichroism spectrum. Pinnamine exhibited significant acute toxicity against mice. (C) 2000 Elsevier Science Ltd.

Kasarin (1), a novel azetinone compound, was isolated from a marine microorganism. The gross structure of kasarin was elucidated by spectroscopic analyses. Kasarin exhibited antibacterial activity and weak cytotoxicity.

Two new lipopeptides, amamistatins A (1) and B, were isolated from an actinomycete. The absolute stereostructure of 1 was determined by spectroscopic and chemical analyses. Amamistatins A (1) and B showed growth inhibition for human tumor cell lines.

Aurilol (1), a novel cytotoxic bromotriterpene, was isolated from the sea hare Dolabella auricularia. The structure of 1, including the absolute stereochemistry of the five stereocenters, was determined by spectroscopic and chemical analyses. Aurilol (1) exhibited cytotoxicity against HeLa S3 cells with an IC50 of 4.3 μg/mL.

The synthesis of the aglycon of aurisides A and B was achieved from (R)-pantolactone in 29 steps using the Nozaki reaction and the Yamaguchi macrolactonization as key steps.

Aurilide (1), a novel cyclodepsipeptide isolated from the Japanese sea hare Dolabella auricularia, was enantioselectively synthesized, and the present result unambiguously confirmed its stereostructure. In addition, the cytotoxicity of 1 was evaluated by employing synthetic 1.

Two new cytotoxic 24-membered macrolides, dolabelides C and D, were isolated from the Japanese sea hare Dolabella auricularia. Their gross structures were deduced by spectroscopic analysis including the 2D NMR technique, and their absolute stereochemistry was determined by means of chemical correlation with the known dolabelide A. Dolabelides C and D exhibited cytotoxicities against HeLa S3 cells with IC50 values of 1.9 and 1.5 μg/mL, respectively.