Marine life is rich in active substances. In this paper, terpenoids and glycosides isolated from marine organisms at home and abroad in recent three years are reviewed, and their research trends are prospected. These newly discovered terpenoids are widely distributed in marine organisms such as algae, corals, sponges and some marine fungi, and mainly exist in the form of monoterpenes, sesquiterpenes, diterpenes and triterpenoids. However, glycosides mainly exist in marine organisms such as algae, sponges, sea cucumbers and starfish in the form of glycosides, steroidal glycosides and terpenoid glycosides.

Marine terpenoid glycosides; biological activity

Marine life shows some important biological activities. The research progress of terpenoids and glycosides in marine organisms at home and abroad since 2005 was reviewed, which provided scientific basis for rational development and utilization. Terpenoids mainly exist in seaweeds, corals, sponges and some fungi in the form of monoterpenes, sesquiterpenes, diterpenes and triterpenoids. And terpenoid glycosides are distributed in seaweeds, sponges, sea cucumbers and starfish.

Keywords marine life; Terpenoids; Glycosides; biological activity

The ocean is the source of life. Due to the particularity of marine environment, it has extreme life environment such as high pressure, low nutrition, low temperature (especially deep sea), no light, local high temperature and high salt. Marine organisms adapt to the unique living environment of the ocean, which will inevitably create a unique metabolic pathway and genetic background for marine organisms, and there will inevitably be many new compounds with new structural types and special biological activities that terrestrial organisms have not found.

Terpenoids are natural hydrocarbons, and their molecules contain the basic unit of isoprene (C5H8). Therefore, all compounds derived from isoprene are called terpenoids or isoprene, whose molecular formula conforms to the general formula (C5 H8) n, but in some cases, due to methyl migration or carbon skeleton rearrangement caused by carbocation, alkylation, degradation and other reasons, a certain segment of the molecule will not completely follow the isoprene law, resulting in some deformed carbon skeletons, which still belong to terpenoids. Terpenoids in marine life are mainly monoterpenes, sesquiterpenes, diterpenes and sesquiterpenes, while triterpenoids and tetraterpenes are few in species and quantity, and most of them exist in the form of glycosides. Terpenoids are important components of marine bioactive substances, which are widely distributed in marine organisms such as algae, corals, sponges and molluscs. And has cytotoxic, antitumor, bactericidal and analgesic activities.

There are many ways to classify glycosides, which can be divided into primary glycosides and secondary glycosides according to whether they are primary or secondary in organisms (primary glycosides are called secondary glycosides or secondary glycosides when more than one glycoside is removed); According to the number of monosaccharide groups contained in glycosides, glycosides can be divided into monosaccharide glycosides, disaccharide glycosides, triglycosides and so on. Glycosides can be divided into saponins and cardiac glycosides according to some special chemical properties or physiological activities. According to the chemical structure types of aglycones, aglycones can be divided into flavonoid glycosides, anthraquinone glycosides, alkaloid glycosides, triterpenoid glycosides and so on. Most marine glycosides are classified according to this feature, mainly including sphingolipid glycosides, steroid glycosides, terpenoid glycosides and macrolide glycosides. Glycosides exist in many marine organisms, such as algae, corals, sea cucumbers and sponges. Previous studies have shown that most marine glycosides have antitumor, antiviral, anti-inflammatory, antibacterial and immune enhancement activities. Ara-C(d- arabincytosine) 1, Ara-A 2 and N4-C 16- 19 saturated fatty acylated derivatives 3 of Ara-C are successful development models of marine glycosides [1].

In this paper, terpenoids and glycosides isolated from marine organisms at home and abroad since 2005 are reviewed.

1 terpenoids

1. 1 monoterpene In 2005, M.G. Knodt et al. [2] studied the activities of three kinds of polyhalogenated monoterpenes, namely, plocaralides A-C (1~ 3) [3,4] isolated from red algae, and found the compound Plocaralides B(2).

1.2 sesquiterpene Two new sesquiterpene compounds, 6-epi-ophioporin G (4) and 6-epi-ophioporin N (5), were isolated from the fermentation broth of Chlorococcus versicolor GF 10 in marine sludge. At the concentration of1~ 3 microns, the compound can induce the apoptosis of neural 2A cells. Ophiolite is a natural tricyclic or tetracyclic sesquiterpene compound, which has universal inhibitory activity on nematodes, fungi, bacteria and tumor cells.

Willam Fenikar et al. isolated an actinomycete CNH-099 from marine sediments, and isolated novel marinonc derivatives neomarinone(6), isomarinone(7), hydroxydebrominone (8) and methoxyEuromomarinone (9) with cytotoxic effects from the metabolites of this strain, all of which are sesquiterpene naphthoquinone antibiotics. Neomarinone(6) and Marinones (7 ~ 9) showed moderate cytotoxicity (IC50=8μg/ml) to HCLLL 6 colon cancer cells in vitro, and neomarinone(6) also showed moderate cytotoxicity to NCI-s60 cancer cells (IC50 = 10μ g/ml) [6].

The compound platycladin sesquiterpene (10 ~ 12) was isolated from the red algae L. microcladia collected from the boundless island of Cios in northern Greece. Red algae was extracted with organic solvent CH2Cl2/MeOH (3: 1), and the eluent was cyclohexane /EtOAc(9: 1). Finally, the compound was purified by HPLC (10- 12). The activity of these compounds was also studied, and it was found that all three compounds had inhibitory effects on lung cancer cells -N6 and A-549. Compound (10): IC50 = 196.9 microns (non-small cell lung cancer -N6) and 242.8 microns (A-549), compound (1 1): IC50 = 73.4 microns (non-small) Compound (12): IC50 = 83.7μ m (non-small cell lung cancer -N6) and 865438, the cytotoxicity of the latter two compounds to lung cancer cells was significantly higher than that of the first compound. It is speculated that the existence of phenolic hydroxyl group and pentacyclic double bond in the structure of the latter two compounds may improve the activity of the compounds, but the existence of bromine atom in the compounds has no effect on their activity. Four sesquiterpenes were also isolated from the red algae collected in Gangcun, China, namely, laurperoxide (13), 10- bromosaponin (14), isobromolauryl alcohol (15) and 65438. Five kinds of sesquiterpenes (17 ~ 21) were isolated from red algae L. luzonensis [9].

Four nitrogen-containing Eucalyptus sesquiterpenes Haliconadins A-D (22 ~ 25) [10] were isolated from cartilaginous fish. Sponges were collected at Tianyun Port in Okinawa, Japan, and 2.5 kg samples were dissolved in 4L methanol. The obtained 1 15g methanol extract was extracted with 1200ml ethyl acetate and 400MlH2O, respectively. 7.9g ethyl acetate extract was subjected to silica gel column chromatography, and methanol/chloroform (95:5) and petroleum ether/ether (9: 1) were used as eluents to obtain compounds A-D (22 ~ 25) and known compounds Akane B and C. The activity test showed that compounds A-D had antibacterial activity, and compounds B and C also had antifungal activity. The IC50 of compound halichonadins C against Cryptococcus neoformans reached 0.0625μg/ml. Three partially cyclized sesquiterpenes (26 ~ 28) have the activity of inhibiting phosphatase Cdc25B, and they are isolated from the fruits of Nitraria spinosa. [1 1]. Frozen sponge samples were soaked in deionized water at 4℃ and freeze-dried, and then extracted with methanol/dichloromethane (1: 1) and methanol /H2O(9: 1) to obtain crude extracts. The crude extract (IC50=8μg/ml) was further separated by activity tracing, and it was dissolved in 100 ml methanol /H2O(9∶ 1) to obtain 1.2g crude extract, and 300ml n-hexane was added to obtain a water phase partially dissolved in methanol /H2O(7∶3). The fraction extracted with 300ml CH2Cl2 showed the strongest inhibitory activity against phosphatase (IC50=6μg/ml), and then the partially cyclized sesquiterpene compound (26) 16- oxo-luffae lactone (12 mg, tr = Compound (27) 16- hydroxy-luffaolide (2.5mg) Five sesquiterpenes, Hyrtiosins A-E (29 ~ 33), were isolated from China Hainan.

Oxidized sesquiterpene compounds gibberellin (34), gibberellin peroxide (35) and gibberellin (36) were isolated from Taiwan Province soft coral Gibberella [13], and compound (35) had mild cytotoxicity [14]. Seven sesquiterpene metabolites (37 ~ 43) extracted from coral [15]. , which contains the skeleton structure of olive, eucalyptus and Ji Ma, has been shown to have a mild inhibitory effect on plasmodium yunis.

1.3 diterpenoids were rarely isolated from green algae before, but compared with 2004, the number of extracted metabolites increased [16]. Many new diterpenoids were isolated from the green algae Dryopteris fusca in Tasmania, Australia. Among them, compounds (44-48) were extracted from unbranched green algae [17], while ester terpenoids (49) were obtained from branched green algae. The study also showed that the extracted ester terpenoids were toxic to cells, fish and microorganisms in different degrees [17].

Koyama K et al. in Japan isolated a new diterpene compound Phomactin H (50) [19] from an unknown marine fungus (MPUC 046) from brown algae Ishige okamurae. Fungus (MPUC 046) was fermented for 3 1 day at 25℃ in 400ml seawater containing 150g wheat, and then extracted with CHCl3 solvent, and Phomactin H was obtained by silica gel chromatography and HPLC purification. Like the discovered phomactin A-G compound, this compound belongs to platelet activating factor (PAF) antagonist, which can inhibit platelet aggregation induced by PAF. It is speculated that this activity is related to a specific skeleton structure of this compound.

Five new polar acyclic diterpenoids (5 1 ~ 55) were isolated from the Bifurcaria bifurcation of brown algae collected from the Atlantic coast of southern France [20]. Brown algae were extracted by chloroform/methanol (1: 1), and purified by silica gel chromatography (eluents were hexane, ethyl acetate and methanol in different proportions) and reversed-phase C- 18 column high performance liquid chromatography to obtain 12 compounds, of which 5 were new diterpenoids. Compound (5 1 ~ 53) was found in the eluent of hexane: ethyl acetate (2:3), while compounds (54) and (55) were obtained in the eluent of hexane: ethyl acetate (1:4).

Six new diterpenoids (56 ~ 6 1) of Dactylomelane were isolated from the red algae Aphrodite collected from Canary Islands, south of Tenerife Island, Spain. Their structures have new cyclic carbon structures ranging from C-6 to C- 1 1. The collected red algae were extracted with organic solvent CH2Cl2/MeOH( 1: 1), and then separated by reversed-phase chromatography with hexane/chcl3/MeOH (2:1:1) as the eluent. Combined with HPLC, the selected fractions were separated by ETAC/MeOH as the eluent. Diterpene luzodiol (62) [9] was also isolated from red algae L. luzonensis. A brominated diterpenoid compound (63) was isolated from other red algae species in Japan [22].

Xenicane diterpenoids (64 ~ 7 1) were isolated from the coral Xenia blumi in Taiwan Province Province, while the compounds Xeniolactones A-C (72 ~ 74) were isolated from Xenia florida in Taiwan Province Province [23]. Compounds (64-67), (69), (70) and (72) have slight cytotoxicity. Xenibellal (75), a non-Xenicane metabolite, also has a slight cytotoxic effect on the umbelliform flower Xenia [24]. Compound Confertdiate (76) is a tetracyclic diterpene, which was isolated from China coral conferta [25].

Actiniarins A-C (77 ~ 79), a diterpene isolated from Anemone collected by Smithsonian Cancer Institute, can moderately inhibit the recombination of human cdc25B phosphatase [26]. Periconicins A, B (80 ~ 8 1) [27] are new diterpenoids isolated from endophytic mangrove fungus Periconia sp. It can inhibit the growth activity of different microorganisms, such as Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6358p and Staphylococcus epidermidis ATCC 12228.

Nanhai fungus 2492# was isolated from the mangrove plant Dianthus australis in Hong Kong. Two diterpenoids (82 ~ 83) isolated from the fermentation broth of 2492# strain have good physiological activities [28], such as anti-tumor, anti-hypertension and arrhythmia regulation. At the same time, the effect of lowering blood pressure and regulating arrhythmia is better than that of clinical positive control under the same conditions.

Diterpenoids (84 ~ 86) were isolated from the mangrove plant Bruguiera gymnorrhiza. Compound (86) has appropriate cytotoxic activity on mouse fibroblasts [29]. Three diterpenoids (87 ~ 89) were also isolated from Bruguiera gymnorrhiza. Rhynchopetala, another mangrove plant in China [30]. Diterpenoids (90 ~ 93) with similar structures were isolated from Bruguiera gymnorrhiza, among which compounds (92) and (93) had slight cytotoxicity [3 1].

1.4 sesquiterpene compound aspergilloxide (94) was isolated from marine fungus Aspergillus (strain number CNM-7 13) by the research group of sesquiterpene Jifanfennik. The compound is a new skeleton with 25 carbon atoms, and it is weak to human colon cancer cell HCT- 1 16. Prior to this, Willam Fenikar and others also isolated a fungus Fusarium heterosporum CNC-477 from the driftwood of mangrove forests in Bahamas, and isolated a series of new polyhydroxysesquiterpene mangiferol A-C (95 ~ 97) [33] and mangiferol A-G (98 ~ 104) [6]. The skeleton of new mangiferol is a 25-carbon sesquiterpene, which was first isolated from natural products. Pharmacological experiments showed that the inhibitory ability of compound (96) on Gram-positive bacteria was almost the same as that of gentamicin, and compounds (98) and (99) had anti-inflammatory activities on mouse ear edema induced by MPA (phorbol myristate acetate). 1.5 Triterpenoids Triterpenoids extracted from marine organisms mainly exist in the form of triterpenoid saponins, triterpenoids and triterpenoid glycosides. Tetracyclic triterpenoid saponins nobilisidenol (105) and (106) were isolated from China sea cucumber [34]. The black-breasted sea cucumber collected from Dongshan, Fujian Province was cleaned and chopped, and extracted with 85% ethanol. Evenly dispersing the obtained fluid extract in water, and then sequentially extracting with petroleum ether, dichloromethane and n-butanol. It was found that the n-butanol extract was separated by macroporous adsorption resin, conventional silica gel chromatography, reversed-phase C- 18 silica gel column chromatography and reversed-phase C- 18 column HPLC to obtain triterpenoid saponins. Yi et al. also extracted other triterpenoid glycosides and triterpenoid saponin desulfurization derivatives from sea cucumber [35, 36]. Triterpene compound Intercede SD-I (107-1kloc-0/2) was isolated from China sea cucumber Mensamaria intercedens, and it has cytotoxic effect [37]. New Zealand sea cucumber Australostichopus mollis is the source of monosulfate triterpenoid glycosides mollisides A (1 13), B 1 (1 14) and B2( 1 15).

Triterpenoids with cytolytic activity, sodwannone S( 1 16), were isolated from the sponge Axinella weltneri collected from the Indian Ocean Hairy Island [39]. Triterpenoid glycoside sarasinoides J-M (1120) was isolated from the sponge Melophlus sarassinorum collected in Sulawesi, Indonesia, and had antibacterial activity against Bacillus subtilis and Saccharomyces cerevisiae [40].

Two glycoside compounds

An unsaturated glycosyl glyceride compound (12 1) [4 1] was isolated from dinoflagellate collected from Hainan. Dinoflagellate was collected from Sanya, Hainan, China. Aspergillus catarrhalis was isolated and extracted with toluene/methanol (1:3) organic solvent. The dried products were extracted with toluene and 1N NaCl aqueous solution respectively. It was found that the organic phase extract was passed through silica gel column (eluent was methanol/chloroform in different proportions), reversed-phase C- 18 silica gel column chromatography (eluent was methanol /H2O=9: 1), and finally preparative HPLC was passed through reversed-phase C- 18 column (mobile phase was methanol /H2O =95:5).

Two monoglycerides, homaxinolin( 123) and (124), phosphatidylcholine homaxinolin( 125) and fatty acid (126), were isolated from Korean sponge Homaxinella sp. Erylosides K (127) and L( 128), two steroidal glycosides isolated from Erylus lendenfeldi, a sponge collected from the Red Sea, can selectively inhibit the rad50 buds of yeast strains, and rad50 can repair damaged double-stranded DNA [44].

Stichopus japonicus is composed of SJC- 1( 129), SJC-2 (130), SJC-3 (13 1), SJC-4 (132). Five compounds were isolated from weakly polar chloroform/methanol, among which SJC- 1 (129), SJC-2 (130) and SJC-3 (13 1) were typical sphingolipids or plant sphingolipids. SJC-4( 132) and SJC-5( 133) also contain hydroxylated fatty acyl structure, but contain unique sphingolipid groups, which are two new glucocerebrosides. Linciacerebroside A (134) is a new glycoside compound isolated from Japanese starfish Linckia laevigata [46].

Steroid glycosides pregnane-5,20-diene -3β- alcohol -3-O-α-L- pyranoside (135) and pregnane-5,20-diene -3β- alcohol -3-O-β-D- xylopyranoside (65438+) Concentrate under reduce pressure to obtain dark brown extract 168, gradient eluting with petroleum ether and ethyl acetate (20:80), separating the eluate by reversed-phase C- 18 column high performance liquid chromatography, and eluting with methanol to obtain 60mg( 135) and 3mg( 136) compounds.

Four steroidal glycosides (137-140) were isolated from the ethanol/dichloromethane extract of Juncus corallina in China [48].

3 Conclusion

At present, the number of natural terpenoids and glycosides found in marine organisms has gradually increased in recent years. Some compounds are promising drug lead compounds with definite activity and strong activity, but relatively few compounds are used in clinical research, so it is necessary to develop more new natural compounds. Secondly, the active compounds found in marine organisms also have problems such as low activity or high toxicity, and their structures can be modified to achieve the best results. In addition, the content of active compounds extracted from marine organisms is usually low, and the compounds are affected by external factors such as extraction reagents and methods. Therefore, semi-synthesis or total synthesis of compounds by chemical synthesis can solve the shortcomings of volatile structure and large reagent consumption in the extraction process. For example, cephalosporin C with new structure and antibacterial, anticancer and neurocardiovascular activities was isolated from marine fungi. It is a famous class of semi-synthetic antibiotics and has been widely used in clinic [49]. Therefore, synthetic or semi-synthetic methods are usually used to solve the large-scale production mode of active compounds as drug sources. We expect these drug lead compounds to play an important role in drug development.