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Croissamide, a proline-rich cyclic peptide that contains an N-prenylated tryptophan, was isolated from a marine cyanobacterium Symploca sp. Its gross structure was determined by spectroscopic analyses, and the absolute configuration was established based on chiral HPLC analyses of acid hydrolysates.

The first total synthesis of janadolide, a new cyclic polyketide-peptide hybrid possessing a tert-butyl group, is described. The synthesis of an unsaturated hydroxycarboxylic acid was effected via the lithiation of vinyl iodide followed by addition to a Weinreb amide with a tert-butyl group and stereoselective 1,2-reduction. The cyclic structure was constructed by macrolactamization at the amide bond between the proline moiety and fatty acid moiety.

A new polyketide with a cis-fused decalin ring scaffold, caldorin, was isolated from the marine cyanobacterium Caldora penicillata. The gross structure and relative configuration were elucidated by spectroscopic analyses. We also clarified that caldorin is a weak SOAT inhibitor and moderate osteoblast differentiation inhibitor. On the other hand, caldorin did not exhibit cytotoxicity against either HeLa or HL60 cells.

Lingaoamide (1), a new cyclic heptapeptide natural product, was isolated from a freshwater Oscillatoria cyanobacterium. The producing organism was collected in Chinese water spinach paddy farm fields in Lingao County, Hainan, China. The structure of 1 was determined by conventional mass spectrometry, NMR spectroscopy, and chemical degradation studies. Lingaoamide concentration-dependently up-regulates the biogenesis of pro-pathogenic melanin pigments (melanogenesis) in the rice blast fungus, Magnaporthe grisea, when tested in vitro. This molecule also exhibits weak in vitro inhibition (MIC 32 μg/mL) of Gram-negative Pseudomonas aeruginosa and Gram-positive Bacillus pumilus, and does not appear to impact plant growth or immune response in vivo using the model organism, Arabidopsis thaliana.

Urumamide, a novel cyclic depsipeptide that contains a β-amino acid, was isolated from a marine cyanobacterium Okeania sp. Its gross structure was determined by spectroscopic analyses, and the absolute configuration was established based on Marfey’s analyses and chiral HPLC analyses of hydrolysis products. Biologically, urumamide inhibited the growth of human cancer cells. In addition, urumamide inhibited chymotrypsin.

Wedelia chinensis has been widely used as a traditional medicine and several bioactive compounds have been isolated. We investigated phytotoxic property and phytotoxic substances in the species. An aqueous methanol extract of W. chinensis inhibited the growth of roots and shoots of cress. The extracts were then purified by several chromatographic runs with monitoring the inhibitory activity and a phytotoxic substance was isolated. The substance was determined by spectral data to be a novel kaurene-type compound, wedelienone. Wedelienone inhibited the growth of cress and timothy (Phleum pratense L) at concentrations greater than 10–30 μM. These results suggest that wedelienone may contribute to the phytotoxic effects caused by the extracts.

The first total synthesis of koshikalide, a 14-membered macrolide that contains three olefins, was achieved. The skipped diene in the cyclic system was efficiently constructed by very mild Stille coupling at low temperature. The absolute stereochemistry was established by comparison of the specific optical rotations of natural and synthesized koshikalide.

Three novel compounds, yoshinones A, B1, and B2, were isolated from the marine cyanobacterium Leptolyngbya sp., and their structures were elucidated by NMR spectral analysis. Yoshinone A, but not yoshinone B1 or B2, inhibited the differentiation of 3T3-L1 cells into adipocytes. In addition, yoshinone A did not exhibit cytotoxicity, suggesting that yoshinone A may be useful in studies on the treatment of obesity.

The first total synthesis of maedamide, an acyclic peptide isolated from a marine cyanobacterial assemblage of Lyngbya sp., was achieved. This synthesis led to reassignment of the allo - d -Ile of maedamide to be l -Ile, which was supported by 1 H and 13 C NMR data.

Maedamide, a novel chymotrypsin-inhibiting depsipeptide, was isolated from a cyanobacterial assemblage that mostly consisted of Lyngbya sp. Its structure was elucidated by spectroscopic analyses and chiral HPLC analyses of hydrolysis products. Maedamide selectively inhibited chymotrypsin but not elastase and trypsin. In addition, Maedamide strongly inhibited the growth of HeLa cells and HL60 cells.

Mycalolide analog 4, consisting only of the side chain of mycalolide B (2), was stereoselectively synthesized and was found to have strong actin-depolymerizing activity.

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.

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.

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.

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.

Four diastereomers of palau’amide (1–4), a cytotoxic cyclodepsipeptide, were synthesized. The 1H NMR spectrum of 1 was identical to that of natural palau’amide. This established the complete stereostructure of palau’amide.

The C11–C22 and C23–C35 segments 2 and 3 of reidispongiolide A (1), an actin-depolymerizing marine macrolide, were synthesized enantioselectively in 12 steps from (R)-glycidyl trityl ether and in 12 steps from chiral ketone 15, respectively.

Novel macrolides, haterumalides NA ( 1 ), NB ( 2 ), NC ( 3 ), ND ( 4 ), and NE ( 5 ), were isolated from an Okinawan sponge Ircinia sp. The absolute stereostructure of 1 was determined by spectroscopic analysis and modified Mosher's method. Haterumalide NA ( 1 ) showed cytotoxicity against P388 cells and acute toxicity against mice.

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.

The bioassay-guided fractionation of the cytotoxic constituents of the Okinawan ascidian Didemnum molle led to the isolation of hexamollamide ( 1 ), a hexapeptide. The gross structure and relative stereostructure of 1 were established by spectroscopic analysis including 2D NMR techniques and single-crystal X-ray diffraction analysis. The absolute stereostructure was determined by chiral HPLC analysis of acid hydrolysates of 1 . Hexamollamide ( 1 ) exhibits moderate cytotoxicity against HeLa S 3 cells.

The trifluoroacetate salt of cinachyramine (1) was isolated from the Okinawan sponge Cinachyrella sp. This structure was determined by the spectroscopic analysis and the degradation under acidic conditions. Cinachyramine (1) is a novel alkaloid with an unprecedented cage system possessing a hydrazone and two aminals.

Aurilide ( 1 ), a new 26-membered cyclodepsipeptide, has been isolated from the Japanese sea hare Dolabella auricularia . The gross structure of 1 was established by spectroscopic analysis. The absolute stereostructure of 1 was determined by HPLC analysis of amino acid components and isoleucic acid obtained from acidic hydrolysis of 1 and by the enantioselective synthesis of the tris( p -bromobenzoate) 3 derived from the dihydroxy acid moiety.

Two new polypropionates, auripyrones A ( 1 ) and B ( 2 ), have been isolated as cytotoxins from the sea hare Dolabella auricularia . The gross structures of 1 and 2 were determined by spectroscopic analysis, and their relative stereochemistry except for the ester moiety of 2 was established on the basis of the NOESY data.

Synthesis of aplyronines B and C, the congeners of aplyronine A, was achieved enantioselectively, which established their stereostructures.

A novel cytotoxic compound, nakiterpiosin (1), was isolated from the Okinawan sponge Terpios hoshinota. Its structure was determined by spectroscopic analysis. The absolute stereostructure of 1 was also determined by a modified Mosher's method. Nakiterpiosin showed potent cytotoxicity against P388 cells.

The C21–C34 segment 2 of aplyronine A (1), a potent antitumor substance of marine origin, was synthesized enantioselectively in 25 steps (17% overall yield) from imide 11.

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.

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.

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.

A 14-membered macrolide, koshikalide (1), was isolated from the marine cyanobacterium Lyngbya sp., and its planar structure was elucidated by spectroscopic analysis. The relative stereochemistry of C-11 and C-13 was elucidated by NOESY experiments and by an analysis of 1H–1H coupling constants. Koshikalide (1) exhibited weak cytotoxicity against HeLa S3 cells.