Cytotoxic macrolides from a cultured marine dinoflagellate of the genus Amphidinium

A fourth cytotoxic macrolide, amphidinolide D[1], together with known amphidinolide B[2], has been isolated from a different batch of the cultured dinoflagellate Amphidinium sp., which was symbiotically associated with an Okinawan flatworm Amphiscolops sp. Two-dimensional nmr experiments including 1H-detected heteronuclear multiple-bond correlation (HMBC) resulted in the structure assignment of 1 and structure revision of the diene moiety (C-13-C-15) of amphidinolide B.     

Amphidinolides B6 and B7, cytotoxic macrolides from a symbiotic dinoflagellate Amphidinium species

Two 26-membered macrolides, amphidinolides B6 ( 2) and B7 ( 1), have been isolated from a marine symbiotic dinoflagellate Amphidinium sp., and the structures were elucidated on the basis of detailed analyses of 2D NMR data. The relative and absolute configurations for 1 and 2 were assigned by comparison of NMR data and CD data with those of known amphidinolides.     

Bioactive macrolides and polyketides from marine dinoflagellates of the genus Amphidinium

Marine microorganisms such as bacteria, cyanobacteria, dinoflagellates, and others have attracted many natural product chemists as the real producers of marine toxins such as fish and algal poisons as well as bioactive substances isolated from marine invertebrates such as sponges and tunicates. Among marine microorganisms, dinoflagellates have proved to be important sources of marine toxins and have been investigated worldwide by natural product chemists. We have continued investigations on chemically interesting and biologically significant secondary metabolites from Amphidinium spp., of a genus of symbiotic marine dinoflagellates separated from inside cells of Okinawan marine flatworms. This review covers the results described in our recent publications on a series of cytotoxic macrolides, designated amphidinolides, and long-chain polyketides isolated from Amphidinium spp. In this review, topics include the isolation, structure elucidation, synthesis, biosynthesis, and bioactivity of amphidinolides and long-chain polyketides.     

Wortmannilactones A-D, 22-membered triene macrolides from Talaromyces wortmannii

The fungus Talaromyces wortmannii, isolated from a soil sample collected in China's Yunnan province, produced four novel 22-membered macrolides, namely, wortmannilactones A-D (1-4). Structures 1-4 were elucidated by extensive 1D and 2D NMR and MS spectral analyses. Compounds 1-4 exhibited in vitro cytotoxic activity against several human cancer cell lines with IC50 values ranging from 28.7 to 130.5 microM.     

Modiolides A and B,two new 10-membered macrolides from a marine-derived fungus

Two new 10-membered macrolides, modiolides A (1) and B (2), and a new linear pentaketide, modiolin (3), were isolated from the cultured broth of a fungus Paraphaeosphaeria sp. (N-119), which was separated from a marine horse mussel, and the structures were elucidated by spectroscopic data.     

海洋前沟藻属甲藻的次生代谢产物及其生物活性

介绍海洋前沟藻属甲藻近20年来的化学成分及其生物活性研究进展。前沟藻属甲藻的主要化学成分有polyketides、大环内酯和半乳糖甘油酯。其中polyketides有amphidinoketides、amphidinols、luteophanols、colopsinols、amphinin 5种类型。从前沟藻属甲藻中分离得到的主要单体化合物均显示有一定的生物活性，如抗真菌、抗肿瘤和溶血性等。表明前沟藻属甲藻是一个资源可持续利用的活性物质库，值得深入研究。     

Cyclic ether-containing macrolactins, antimicrobial 24-membered isomeric macrolactones from a marine Bacillus sp

Bioassay-guided isolation of bioactive metabolites from the ethyl acetate extract of a marine Bacillus sp. fermentation broth has led to the discovery of three new 24-membered macrolactones, macrolactins 1-3, which contain an oxetane, an epoxide, and a tetrahydropyran ring, respectively. The configurations of 1-3 were assigned by a combination of coupling constants, ROESY data analysis, and application of the modified Mosher's method. Compounds 1-3 showed in vitro antimicrobial activity.     

A new digalactosyl diacylglycerol from a cultured marine dinoflagellate Heterocapsa circularisquama

A new digalactosyl diacylglycerol (1) has been isolated from the cultured marine dinoflagellate Heterocapsa circularisquama together with known monogalactosyl diacylglycerols 2 and 3, and their structures were elucidated by spectroscopic methods. The digalactosyl diacylglycerol 1 showed cytolytic activity toward heart cells of oysters.     

Zooxanthellamide D, a polyhydroxy polyene amide from a marine dinoflagellate, and chemotaxonomic perspective of the Symbiodinium polyols

A long-chain polyhydroxy polyene amide, zooxanthellamide D (ZAD-D, 1, C54H83NO19), was isolated from a cultured marine dinoflagellate of the genus Symbiodinium. ZAD-D (1) is a polyhydroxy amide consisting of a C22-acid part and a C32-amine part and furnishes three tetrahydropyran rings and six isolated butadiene chromophores. The relative stereochemistry of the tetrahydropyran ring systems was elucidated by NMR techniques. This metabolite showed moderate cytotoxicity against two human tumor cell lines. A phylogenetic tree of Symbiodinium has been updated and compared with the structures of the hitherto isolated polyols of Symbiodinium, zooxanthellatoxins and zooxanthellamides, providing a promising chemotaxonomic perspective for the classification of this morphologically indistinguishable dinoflagellate.     

Macrolactins O-R, glycosylated 24-membered lactones from Bacillus sp. AH159-1

In the course of screening for inhibitors of Staphylococcus aureus peptide deformylase, four new glycosylated macrolactin compounds, macrolactins O ( 1), P ( 2), Q ( 3), and R ( 4), along with the known macrolactins B ( 5) and C ( 6), have been isolated from the liquid cultures of Bacillus sp. AH159-1. The structures of compounds 1- 4 were assigned on the basis of MS and NMR data. They inhibited S. aureus peptide deformylase and also showed antibacterial activity against Escherichia coli and Staphylococcus aureus.     

Bahamaolides A and B, antifungal polyene polyol macrolides from the marine actinomycete Streptomyces sp

Bahamaolides A and B (1 and 2), two new 36-membered macrocyclic lactones, were isolated from the culture of the marine actinomycete Streptomyces sp. derived from a sediment sample collected at North Cat Cay in the Bahamas. The planar structures of 1 and 2, bearing a hexaenone and nine consecutive skipped hydroxy groups, were determined by 1D and 2D NMR, mass, IR, and UV spectra. The absolute configurations of the bahamaolides were established by combined multistep chemical reactions and spectroscopic analysis. Bahamaolide A displayed significant inhibitory activity against Candida albicans isocitrate lyase and antifungal activity against various pathogenic fungi.     

Bacteriohopanehexol, a new triterpene from the marine sponge Petrosia species

A new bacteriohopanoid, bacteriohopanehexol was isolated from the marine sponge Petrosia sp., and its structure 1a was established on the basis of the NMR and MS spectroscopic data of its hexaacetate derivative 1b. Bacteriohopanehexol is most likely a bacterial metabolite.     

Hygrocins a and B, naphthoquinone macrolides from Streptomyces hygroscopicus

Two new naphthoquinone macrolides, hygrocins A (1) and B (2), were isolated from the fermentation broth of Streptomyces hygroscopicus. Hygrocin A is not stable due to the presence of an active methylene group (C-22), which undergoes intramolecular aldol condensation with the quinone ring to yield a gamma-lactam derivative, 6. Its structural elucidation was achieved by chemical conversion to 3, an unusual diazomethane derivative, and confirmed by its alkaline hydrolysis product 4, hydrogenation derivative 5, and "degradation" product 6. The structure of hygrocin B was determined by combined chemical and spectroscopic methods.     

Luffariolides H and J,new sesterterpenes from a marine sponge Luffariella species

Two new sesterterpenoids, luffariolides H (1) and J (2), have been isolated from an Okinawan marine sponge Luffariella sp. The structures of 1 and 2 were elucidated on the basis of spectroscopic data.     

Characterization of spirolides a, c, and 13-desmethyl c, new marine toxins isolated from toxic plankton and contaminated shellfish

Three additional marine toxins, spirolides A (1), C (3), and 13-desmethyl-C (7), were isolated from contaminated scallops and phytoplankton collections obtained from a Nova Scotian aquaculture site, as well as from batch cultures of the dinoflagellate Alexandrium ostenfeldii obtained as a single-cell isolate from these phytoplankton assemblages. The structures of these new spirolide derivatives, characterized by mass spectrometry and NMR, indicate a close relationship with spirolides B (2) and D (4) isolated previously from contaminated shellfish in the same area. All of these compounds display "fast-acting" toxicity in the traditional bioassay used for monitoring shellfish, and this is related to the presence of a cyclic imine function in all these compounds. Those spirolides containing a vicinal dimethyl group in the seven-membered ring are resistant to oxalic acid hydrolysis, whereas those that do not are readily hydrolyzed. These observations suggest that the extra methyl group on the seven-membered imine ring of 3, 4, and 7 appears to block the process of imine hydrolysis perhaps by stereochemical interference.     

Novel polyketide metabolites from a species of marine fungi

Fermentation of a marine fungal species obtained from a tissue sample of a marine sponge collected in Indonesia in October 1996, yielded the novel hexaketide compounds iso-cladospolide B (1); seco-patulolide C (2); the 12-membered macrolides, pandangolide 1 (3) and pandangolide 2 (4); and the known terrestrial fungal metabolite, cladospolide B (5).     

Clathrins A-C: metabolites from a Southern Australian marine sponge, clathria species

A Clathria sp. collected in the Great Australian Bight has yielded the novel metabolites clathrins A (6), B (7), and C (8). Structures were assigned to clathrins A-C on the basis of spectroscopic analysis. Clathrin A (6) represents a plausible biosynthetic intermediate that provides an inferred link between marine sesquiterpene/benzenoids and mixed terpene/shikimate biosynthesis.     

Haliclonyne, a new highly oxygenated polyacetylene from the marine sponge Haliclona species

Haliclonyne (1), a new polyacetylene carboxylic acid, has been isolated from the marine sponge Haliclona sp. collected in the Gulf of Eilat. The structure of haliclonyne, a C(47) oxo-octahydroxy-dienetetrayne carboxylic acid, was elucidated by interpretation of NMR and mass spectra of 1 and two of its derivatives.     

Phorbasin A: a novel diterpene from a southern australian marine sponge, Phorbas species

A southern Australian Phorbas species has yielded a novel diterpene, phorbasin A (1), possessing an unprecedented carbon skeleton. The structure for phorbasin A was determined by detailed spectroscopic analysis.     

Mirabilin G: a new alkaloid from a southern Australian marine sponge, Clathria species

A Clathria sp. collected during scientific trawling operations in the Great Australian Bight, Australia, has yielded the new alkaloid mirabilin G (1). A structure was secured for 1 by detailed spectroscopic analysis and comparison to known marine alkaloids.