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Review

Brominated Compounds from Marine Sponges of the Genus Aplysina and a Compilation of Their 13C NMR Spectral Data

by
Narlize Silva Lira
1,
Ricardo Carneiro Montes
1,
Josean Fechine Tavares
1,
Marcelo Sobral da Silva
1,
Emidio V. L. da Cunha
2,
Petronio Filgueiras de Athayde-Filho
1,
Luis Cezar Rodrigues
1,
Celidarque da Silva Dias
1,* and
Jose Maria Barbosa-Filho
1,*
1
Laboratory of Pharmaceutical Technology, Federal University of Paraiba, Joao Pessoa 58051-900, PB, Brazil
2
Department of Pharmacy, State University of Paraiba, Campina Grande 58100-000, PB, Brazil
*
Authors to whom correspondence should be addressed.
Mar. Drugs 2011, 9(11), 2316-2368; https://doi.org/10.3390/md9112316
Submission received: 18 August 2011 / Revised: 24 October 2011 / Accepted: 31 October 2011 / Published: 10 November 2011
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Abstract

:
Aplysina is the best representative genus of the family Aplysinidae. Halogenated substances are its main class of metabolites. These substances contribute greatly to the chemotaxonomy and characterization of the sponges belonging to this genus. Due to their pharmacological activities, these alkaloids are of special interest. The chemistry of halogenated substances and of the alkaloids has long been extensively studied in terrestrial organisms, while the number of marine organisms studied has just started to increase in the last decades. This review describes 101 halogenated substances from 14 species of Aplysina from different parts of the world. These substances can be divided into the following classes: bromotyramines (A), cavernicolins (B), hydroverongiaquinols (C), bromotyrosineketals (D), bromotyrosine lactone derivatives (E), oxazolidones (F), spiroisoxazolines (G), verongiabenzenoids (H), verongiaquinols (I), and dibromocyclohexadienes (J). A compilation of their 13C NMR data is also part of the review. For this purpose 138 references were consulted.

1. Introduction

Marine sponges have been known and used by mankind since antiquity. They were included in the first classification of living organisms, written in 350 BC by Aristotle in Greece. At first thought to be plants, their animal nature was only recognized by the end of the XVIII century. However, great naturalists of the time such as Lamarck, Linnaeus and Cuvier classified them as Zoophytes. The elevation of the Porifera to the level of phylum was suggested by Huxley in 1875 and by Sollas in 1884, and was only accepted at the beginning of the XX century [1].
Sponges belong to the phylum Porifera and are the most primitive of multicelled animals, having existed for roughly 700–800 million years. They have a very simple physiology of construction. They are aquatic organisms growing mostly in temperate salt waters but may also be found in fresh water. When reaching adult form, they are found in solid substrates in places that allow adequate conditions for their growth. Some, when in their primary states, may be mobile [2–4]. They are easily found in all marine environments, from the intertidal zones to the ocean depths of 8500 m in tropical and polar seas. Despite their wide distribution in terms of different oceans and depths, the rocky non-polluted coastline areas show greater populations of sponges which are also known for being rich in secondary metabolites [5–9].
The sponges are filtering animals, which utilize flagellate cells called coenocytes for promoting the circulation of the water through a system of canals existing in this phylum only called aquifer system, around which their body is built. This water flow brings organic particles and microorganisms which are filtered and eaten [10]. Of all the known sponges, only 1% grow in fresh water [11].
There are basically three classes of sponges, Calcarea (5 orders and 24 families), Desmospongiae (15 orders and 92 families) and Hexactinellida (6 orders and 20 families). So far, about 15,000 species of sponges have been described, their diversity however is believed to be much bigger than this [4,12]. Being sessile simple organisms, they evolved chemical defense mechanisms to protect themselves against predators and competitors, as well as against infectious microorganisms. Studies show that secondary metabolites in sponges carry out a crucial role in their survival in the marine ecosystem [13,14].
Because of their potential for the production of new substances of pharmacological interest, sponges have been one of the most chemically studied organisms. In the past 20 years, hundreds of substances have been isolated from them and many of those substances have already been identified, and present interesting biological and pharmacological (such as antibacterial, anticoagulant, antifungal, antimalarial, antituberculosis, antiviral, immunosuppressive and neuro-suppressor) activities [15–23]. The main reported activities for the Aplysina genus are antibacterial, antiyeast, antifungal, antiviral, cytotoxic and hyperglycemic activities, which can be seen in Table 1.
The pioneer investigative work in the field of sponge chemistry published by Bergmann and Feeney in the beginning of the 1950s led to the discovery of Cryptotethya crypta bioactive nucleosides spongothymidine and spongouridine [21]. These nucleosides were the basis for the synthesis of Ara-C, the first marine derivative anticancer agent, and antiviral drug Ara-A [22]. Today, Ara-C is used in the routine treatment of patients suffering from leukemia and lymphomas. One of its derivatives was also approved for use in patients with cancer of the pancreas, lungs and breast [23].

The Genus Aplysina

The genus Aplysina, formerly known as Verongia and reclassified to Aplysina, is one of the richest in terms of secondary metabolites, described in 14 species of the family Aplysinidae, there are 2 species from the Mediterranean Sea, 8 from the Caribbean, 3 from the Pacific Coast of Mexico and 15 in the Brazilian coast. Of the above species, 8 have only been recently identified. From the Mediterranean Sea, the two described species of the genus Aplysina are: A. aerophoba (Schmidt, 1862) and A. cavernicola (Vacelet, 1959). From the Caribbean, among others we find A. fistularis insularis, A. fistularis form fulva, A. archeri, A. cauliformis and A. Lacunosa [33].
Like other genera of the order Verongida, Aplysina stands out for its unique biochemical characteristics. They show low terpene content, and possess a moderately high percentage of sterols, mostly within the aplystan skeleton. They also produce a significant series of brominated derivatives of tyrosine metabolites considered peculiar to species of this order. The sponges of this order are also known for their high phenotypic variability [34].
Marine organisms produce a cocktail of halogenated metabolites with potential commercial value. The structures found in these compounds go from linear chain acyclic, to complex polycyclic molecules [35,36]. The research of halogenated metabolites has been more focused on marine algae than on sea sponges [37–41]. Though many compounds have been discovered recently, many sponges species are poorly screened and the need for new drugs keeps this field open.
In a previous paper our research group evaluated crude algae, sponge extracts and chemically determined molecules from Northeastern Brazil [42–48] with database survey [49–62].
In this paper we review halogenated substances from the genus Aplysina. A compilation of the 13C NMR spectral data of the selected natural products is also provided. This type of genus and species investigation is helpful in the identification and capture of halogenated substances from the genus.

2. Methodology

An extensive bibliographic review was carried out to identify studies of halogenated substances isolated from the genus Aplysina. The present review covers the period of 1967 thru 2010. The search was performed using the following databases: NAPRALERT (Natural Products Alert at the University of Illinois, Chicago), Chemical Abstracts, and the Brazilian online scientific literature search system called “Periodical CAPES” (Coordination for the Improvement of Graduate Level Personnel).
Tables 2 and 3 respectively show the halogenated substance distribution in the genus Aplysina, and the basic skeletons of those substances. Table 4 shows the different substituents for the diverse classes of halogenated substances. Table 5 describes the position of the substituents for the 101 substances isolated from each species. Finally Tables 6–14 show a compilation of 13C NMR data of the substances.
Although the isoxazoline alkaloids are the group with more 13C NMR data, some chiral centers of this group continue with an undefined stereochemistry due to the incompatibility of using X-ray crystallography techniques, possessing sometimes non-crystalline characteristic [98]. Some positions with 13C NMR data had to be revised because there were mistakes in the numbering of the carbon skeleton in the attribution of values of some positions in this group of alkaloids.

3. Discussion

The genus Aplysina belongs to the order Verongida, sponges with a wide variety of metabolites. Sterols [110,111], carotenoids [112], amino acids [113] and rare fatty acids [114] have all been isolated from this order. However, the peculiarity of this order is from the ecological and medicinal points of view, in that great production of halogenated substances originates from the metabolism of amino acids such as phenylalanine and tyrosine. The halogenated substances found in the marine sponges of the genus Aplysina can be classified as: (A) Bromotyramines, (B) Cavernicolins, (C) Hydroverongiaquinols, (D) Bromotyrosineketals, (E) Bromotyrosine lactone derivatives, (F) Oxazolidones, (G) Spiroisoxazolines, (H) Verongiabenzenoids, (I) Verongiaquinols and (J) Dibromociclohexadiens.

3.1. Chemotaxonomy Importance of Aplysina Sponges

Although in the past, it was suspected that bromotyrosine compounds were not present in Brazilian Aplysina species [69], nowadays numerous studies have shown the presence of these chemical biomarkers, not only in Brazilian species, but in almost all the Verongida order.
In order to classify the large number of halogenated compounds reviewed in Table 2, for each sponge species, we listed the halogenated compounds under the correlated species. Considering the taxonomic species diagnosis of morphologic variation of spongin fibers is difficult [33], chemical composition can be used as a tool for a more accurate identification. The distribution of the halogenated compounds is widespread in Aplysina genre, and studies show that mainly bromoisoxazoline alkaloids have been found in almost all species. This family of metabolites was usefully employed as a chemical marker for the distinction of some taxa as Aplysina aerophoba and Aplysina cavernicola, two very physically similar species [63], but biochemically different. In another situation, majority of aerothionine was key to identify two subspecies of A. fistularis, which split into A. fulva and A. insularis [115].
The similarity between agelorins A and B, isolated from Agelas oroides and produced by Aplysina caissara, was essential to show the two genera, Aplysina and Agelas, have a phylogenetic relationship [76] and 11-epi-fistularin-3 was yielded by Aplysina fulva [98].
The presence of stereo metabolites isolated from Aplysina sponges as derivatives of fistularin-3 discussed by Rogers et al., 2005 [98], provides evidence that enzymatic pathways are non-stereoselective in these sponges.
As can be seen, each kind of genus adds a different profile of metabolites. However, even with a different chemical profile, Aplysina sp. has compounds that give a clue to their evolutionary origin.

3.2. Bromotyramines

The substances aplyzanzine A, aplysamine-1 and aplysamine-2 present a dibromotyramine structural portion, and probably originated in accordance with Evan et al. [82], by amidation with other bromotyrosinated radicals. Moloka’inamine [116] and purealidin C isolated from Psammaplysilla purea [90] are examples of metabolites isolated from sponges of the order Verongida, having dibromotyramine in their structures. According to Carney, free phenolic groups are important precursors nitrile phenolic [96], hence the similarity between methoxylated compound, aplysamine-2, and hydroxylated analogue, psammaplin-A [84], observed by Xynas and Capon, 1989, shows that psammaplin-A may be important precursor aplysimines as much of the fistularin and its derivatives

3.3. Cavernicolins

Cavernicolines are γ and δ-lactames formed by a residual halogenated tyrosine precursor [81] and also having a bi-cyclic system. The junction of the rings occurs in carbons C-3 and C-4 in ortho position, while in the 7-bromocavernicolenone and in the 7-chlorocavernicolenone, this junction occurs in carbons C-2 and C-4. They can be defined as haloperoxidases with the role of converting either the 3-chloro (V) ortho 3-bromotyrosine (IV) in residues of 3,5-dichloro (VIII) or 3,5-dibromotyrosine (VI) or 3-chloro-5-bromotyrosine (VII) or 3-bromo-5-chlorotyrosine (IX), respectively [80]. These substances have a chiral center at C-2 and their R and S enantiomers are obtained in racemic mixtures, or relatively pure from the genus Aplysina. In the formation of cavernicolines, as to the substitution pattern (ortho or para) it is suggested that the biosynthesis pathway has either a halotyrosine (XV, XVI, XVIII and XVIX) or a halo-dopa (XIV and XVVI) intermediary which will form a spirolactone precursor (XXII and XXIII), allowing the formation of intermediaries in racemic or quasi-racemic mixtures. The absence of control in the absolute stereochemistry of this class is intrinsic to phenol oxidative coupling [81,117]. It is noteworthy that experimental observations [118] show that 3,5-dibromo-4-methoxyphenylalanine methyl ester (XX) in reaction in an anodic oxidative medium form a more appropriate intermediary (XXI) than the spirolactone, originating derivatives similar to the stereoisomers of the cavernicolines with considerable yields (See Figure 1).

3.4. Hydroverongiaquinols

The hydroverongiaquinols are 2,6-bromotyrosine phenolic derivatives. Both the hydroverongiaquinols and the verongiabenzenoids are important mediators in biosynthesis of other classes of bromotyrosine metabolites. The verongiabenzenoids are part of the biosynthesis of isoxazoline alkaloids, and hydroverongiaquinols are important precursors in the formation of metabolites which need free phenolic groups to convert themselves into α-oximine substances, such as the phenolic nitriles. However, phenolic nitriles have not been found in the genus Aplysina, they are found in the genus Ianthella where substances like the bastadins, are important chemotaxonomic markers for the genus [119].

3.5. Bromotyrosineketals

The bromotyrosineketals have a 3,5-dibromocyclohexa-2,5-dienyl ketal skeleton system. Literature shows that the dimethoxy and methoxy-ethoxy ketals (XXXII) isolated from Aplysina fistularis and from Aplysina cauliformis [92,93,120], are artifacts formed by the oxidation of dienone, since the dimethoxy form is obtained as a mixture of diastereoisomers [94,95], both showing antibacterial activity. Further evidence that they are artifacts is the formation of dimethoxy and methoxy-ethoxy ketals which can be explained as being formed from an arene (dienone intermediary XII), which suffers 1,4 additions of methanol, water or ethanol (Figure 2), and displayed a reaction described by Kasperek et al. [94,95,121]. However, the methoxy-butoxy and methoxy-pentoxy ketals isolated from Aplysina thiona [109] are not considered reaction products. Aplysinketal A was isolated only in the form of diastereoisomers, and the absence of the dimethoxy ketal indicates the non-existence of reactions during the extraction process [109]. It has been suggested that the formation of the C4 and C5 chains are formed via lysine and ornithine respectively (Figure 2) [104,114].

3.6. Bromotyrosine Lactone Derivatives

The bromotyrosine lactone derivatives, with the exception of aplysinimine which is an imine, are five member lactones condensated with 3,5-dibromotyrosine residues (XXIV). Aeroplysinin-2 is different from the others because it has a cyclodiene group instead of an aromatic ring, while aplysinadiene presents a cis-trans diene side chain. It is proposed that the biosynthesis of this class of substances has an imine-ether (XXXIV) as initial intermediary, a hydroxylated derivative of aplysinimine. This derivative will either suffer a tertiary alcohol dehydration to form aplysinimine [109,120] or will follow other biosynthetic pathways similarly to bromotyrosine lactones as aeroplysinin-2, or the verongiabenzenoids and verongiaquinols, in this case the intermediary suffers dehydroxylation and demethylation and can form artifacts such as dimethoxys and methoxy-ethoxy ketals. [122]. Aplysinolide is considered an artifact, since it possesses an α,β-unsaturated side chain which is uncommon to find linked to a lactone ring. In accordance to Cruz et al. [109] this substance can be formed by combining aplysinimine with Me2CO during the purification process (see Figure 1).

3.7. Oxazolidones

Oxazolidones are very common in Aplysina, but just two types are found: diastereoisomers of bisoxazolidone and methoxy derivative. This derivative presents two chiral centers with different stereochemistries for different species. Studies show that these bisoxazolidone’s isomers have a relative configuration of 7S*, 11R* [97] and 11R*, 7S* [106], as determined by comparison with bisoxazolidone isolated from Ascidia Clavelina oblonga [123] and an absolute configuration R, R [64] obtained by X-ray crystallography. There are evidences that fistularin-3 degradation promotes bisoxazolidone and aeroplysinin-1 production [13].

3.8. Spiroisoxazolines

The spiroisoxazolines also known as isoxazoline alkaloids form the biggest group of Aplysina and Verongid order metabolites. They are divided into two structure types: mono-spirocyclohexadienylisoxazolines and bis-spirocyclohexadienylisoxazolines [124].
The chemical structure of mono-spirocyclohexadienylisoxazolines (nuclei G7, G8) have essentially one spirocyclohexadienylisoxazoline ring bonded to a 1–6 carbon side chain with exception of the spiroisoxazoline acid ester (nucleus G9) [83] considered an artifact of ethanolic condensation from spiroisoxazoline acid [125]. The bis-spirocyclohexadienylisoxazolines (nuclei G1, G2) can present the same ring, which in the more common example is bonded to a 3–11 carbon side chain.
This side chain is bonded to another spirocyclohexadienylisoxazoline ring [124]. In other spiroisoxazolines, the rings suffer oxidation of the methoxy group forming a cyclohexenone (nuclei G3, G4) [74,76,101]. Cyclohexenone also suffers hydroxyl or bromine oxidations originating cyclohexenone epoxide between carbons 1 and 2 and forming oxaspirocyclohexenonylisoxazolines (nuclei G5, G6) [100]
The biosynthetic pathway for spiroisoxazolines needs tyrosine intermediates with O-methyl groups (XXVII), which are metabolized to form oxime grouped intermediates (XXVIII) and shortly thereafter form other intermediaries with arene oxide (XXIX). The nucleophilic attack of the oxime over either the epoxide or the phenol originates by breaking the epoxide which forms the isoxazole ring (XXX) [96]. The C4 or C5 side chains that extend out of the ring such as in aerothionin and inhomoaerothionin are produced via ornithine and lysine respectively (Figure 2) [70,94,95,126]. However, when the side chains present a 4-aminobutanoic substituent it is suspected that the amino acid involved is glutamic acid (Figure 2) [99]. In some spiroisoxazolines such as fistularin-3, and araplysillin N9-sulfamate, there is a 3-amino-1-propanol connector which binds itself to other structures and probably has as a precursor of its biosynthesis a decarboxylated product of the uncommon amino acid, homoserine. This amino acid is an intermediary for the enzyme S-adenosylmethionine (SAM). It is suggested that the SAM is involved in SN2 substitutions of hydroxyl of 3,5-dibromotyrosine (DBT) (XXIV), making it susceptible to the formation of methoxyl groups by methyltransferase and O-alkylated bonds via other enzymes. The enzyme responsible for O-alkylations is putative C3-alanil-methyltransferase which allows 3-amino-1-propanol connector bonding to the DBT residue, forming spiroisoxazoline residue complexes with large molecular masses (XXV) which are then incorporated in the isoxazoline rings [99]. The alkaloid archerine, a dimer of two imidazole rings, is probably formed by oxidative coupling [1 + 1] of two aerophobin-2 molecules [73]. In sponges of the order Verongida, the spherule cells have the capacity of stocking and secreting isoxazoline alkaloids, which are modified by enzymes located in distinct locations [127,128]. The extracts of the majority of the sponges belonging to the genus Aplysina, when tested, show that their enzymes convert brominated isoxazoline alkaloids into aeroplysinin-1 and dienones. Sponges of other orders are unable to perform this biotransformation [129]. Puyana et al. [130] demonstrated that there is no aeroplysinin-1 and dienones production when there is a decrease in the amount of spiroisoxazolines. The ecological function of this enzymatic activation is microbial pathogen growth inhibition and the repellent odor, which decreases the predatory search by fishes [129].
Although the agelocaissarines A1, A2, B1 and B2 were initially considered production artifacts as pairs of stereoisomers, this was later modified by the observation of in vitro experiments showing the absence of substances with relative stereochemistries different to those found in the work [76].
In therapeutics these substances demonstrate tumor cell cytotoxic [22], antimicrobial [15] and antihistamine [73] activity.
Spiroisoxazolines vary in different species, but also inside the single species. While A. fulva produces aerothionin as its major component (0.11%) [34], this same substance is not present in A. insularis [74] and in A. fulva it appears with a larger amount (0.52%) [102]. Nuñez et al. [97], affirms that this chemical variation may be due to either different extraction and isolation techniques, or to biological diversity of the areas in which the sponges are collected. This chemical distinction led to reinforce the hypothesis that Aplysina aerophoba and Aplysina carvernicola have metabolic differences and that A. aerophoba, erroneously identified in the work of Cimino et al. [67], was in fact Aplysina cavernicola.
The presence of hemifistularin, isolated together with 11-oxofistularin-3, begs us to question whether the first is a precursor of 11-oxofistularin-3 biogenesis, or a degradation product [72]. Fistularin-3 shows another type of variability. Besides having stereoisomers of (+) fistularin-3, such as (+)-isofistularin-3 and 11-epi-fistularin-3, the chemical composition of sponges contains them in irregular proportions, which makes it difficult to determine through optical rotation. In order to determine the absolute configuration of fistularin-3 and its stereoisomers, a microscale analysis with Marfey’s reagent, has been used that led to the formation of stable reaction products analyzed by LC-MS [98].

3.9. Verongiabenzenoids

The verongiabenzenoids are aromatic methoxylated substances which present a skeleton with a 2,6-dibromomethoxybenzene nucleus. Biogenetically methoxylated, some verongiabenzenoids can form isoxazolines [13] or epoxide intermediaries from the arene oxide, which leads to forming other verongiabenzenoids [96].

3.10. Verongiaquinols

The chemical structure of the verongiaquinols is either a cyclohexadien-2-one or cyclohexadien-2,6-one system, with either bromine or chlorine substituents in positions 2 and 6 and hydroxyls on carbons C-3 and C-4. They also may suffer ramifications on carbon C-4. The verongiaquinols seem to be related to degradation steps of tyrosine metabolism, as is the case of dienone (XII). The degradation of bromotyrosine substances such as iso-fistularin-1 and aerophobin-2 after mechanical injury led to the formation of aeroplysinin-1 (XXXII) and (XII). It is also noteworthy that the extraction of frozen sponges and consequent exposure to alkaline sea water will form dienones (XII) [97,130,131]. Besides being integrated at the metabolic level, dienone and aeroplysinin-1 have an important defense role for sponges: cytotoxic, algicidic, molluscicide and antibacterial activity have been reported [131,132].
Other verongiaquinols such as 2,6-dibromoquinone have been reported to inhibit the enzyme RNA polymerase II, blocking the initiation of the chain, but not its elongation [133].
It is not known for sure if (1′R,5′S,6′S) and (1′R,5′R,6′S)-2-(3′-5′-dibromo-1′-6′-dihydroxy-4′-oxocyclohex-2′-enyl)-acetonitrile are simple artifacts, as aeroplysinin-1 is able to form them in the presence of acetone by keto-enol tautomerism. However, these acetonitriles are not normally produced as metabolites of aeroplysinin-1 (XXXII) in other species [27].

3.11. Dibromocyclohexadienes

This group is comprised of two substances which present a 1,2-dihydroarene-1,2-diol and may have their biogenesis via an arene oxide (XXXI) in agreement with their stereochemistry [94,95]. Aeroplysinin-1 (XXXII) is a nitrilated substance found in dextro and levorotatory forms. The dextrorotatory isomer (+) aeroplysinin-1, has been obtained from Aplysina aerophoba [70], Aiolocroia crassa, Verongula rigida, Aplysina archeri [71] and Psammoposilla purpurea [134]. (−) Aeroplysinin-1 has been found in Ianthella ardis [135] and Verongula gigantean [71]. The metabolic degradation of bis-oxazolidone, isofistularin-3, aplysinamisin-1 and aerophobin-2 is known to be an important source of aeroplysinin-1 [13]. In terms of pharmacological activity, aeroplysinin-1 is a versatile substance which has demonstrated cytotoxic [134], antiprotozoal [136] and antiangiogenic [137] activities. Aplysifulvin is one of the most recently isolated substances from the sponge A. fulva [97]. It possesses only two methoxies and no ethoxies, and since no ethoxy derivatives were detected, the possibility that aplysifulvin is an artifact has been discarded. Hypothetically, the chemical structure of aplysifulvin suggests that the 3,3-dialkoxy ketals (with OMe and OEt groups) previously described are artifacts [97].

3.12. Structural Elucidation

This section describes the compilation of the 13C chemical shifts of halogenated compounds of the genus Aplysina. All compounds compiled in this review—bromotyramines (1–4), cavernicolins (5–17), hydroverongiaquinols (18–20), bromotyrosineketals (21–24), bromotyrosine lactone derivatives (25–28), oxazolidones (29–32), spiroisoxazolines (33–81), verongiabenzenoids (82–86), verongiaquinols (87–99) and dibromocyclohexadienes (100–101)—have in common 3,5-halotyrosine or halophenylalanine derivatives.
Research data shows that works from the decades of 1970, 1980 and 1990 show little or no information of 13C NMR as compounds (95–97) whose structural elucidation was done by mass spectrometry (MS) and 1H NMR spectroscopy analysis and reactions of structural identification.
The bromotyramine family skeleton can be recognized by the typical 1H-NMR signals, as for example, in the case of compound 1: a singlet for aromatic protons H-2 and H-6 (δ 7.62) and four triples (δ 3.02, 2H, 8.0 Hz; δ 3.50, 2H, 8.0 Hz; δ 4.12, 2H, 5.5 Hz; δ 3.22, 2H, 5.5 Hz) attributed to H-7, H-8, H-1’, H-3’ respectively [84]. When NH-3’ has low electron density as compound 1 positively charged and compound 2 close to electrophilic oxime group, the 13C-NMR signals shift to downfield compared to compounds 3 and 4,whose substituents are methyl groups [84].
Typical 1H NMR data from the cavernicolin class are, in the case of compound 5, for H-3 δ 4.05 (dd, J = 10.1 Hz and J = 1.5 Hz), a singlet for H-5 at δ 7.3 and the signals for NH and OH at 6.9 (s) and 4.4 (s) respectively [83]. 13C NMR data shows that chlorinated carbon have their signals at downfield shifts in relation to bromine carbons as it can be seen, for example, comparing compounds 5 and 6 with 9 and compound 11 with 12.
Biosynthetically, verongiaquinol metabolites are the oxidized form of hydroverongiaquinols, considered as a hydroquinone precursor [124,138]. Therefore, the basic difference in the 13C NMR between these two classes is the downfield signal of ketone carbon C-1 (δ 172.6) of compound 91 compared with hydroxylated C-1 (δ 150.0) of compound 20 [97].
Data analysis of the 13C NMR bromotyrosine lactone family brominated aromatic show carbon signals have more shielded signals compared to the other aromatic signals of the ring. The more is the unsaturated side branching at C-7, more deshielded are the signals of the lactone ring, with the increasing order of introducing the compounds 28, 27 and 26 [64,109].
The carbons of the spiroisoxazolinic system of most compounds with cores G1, G2, G7, G8 and G9 acquire values which become a standard set of values, with the exception of carbons C-2 and C4 values, which seem to be mistakenly exchanged one for another at δ 120 or δ 114, being the correct value of δ 120 for carbon C-2 due to the proximity of the hydroxyl and the C-4 for δ 114.
The mono and bis-spiroisoxazolinic ring systems could be distinguished by double 1H-NMR shield and deshield signals for the two rings, for example, compound 50 shows signals at δ 4.16 (1H, d, J = 8.3 Hz) for H-1 and δ 4.58 (1H, d, J = 7.9 Hz) for H 1’. A typical methylene signal at δ 4.43; 3.47 (2H, ABq, J = 18.2) is attributed to the isoxazol ring protons H-7, 7’ for this compound [29]. Today the most used techniques to elucidate absolute stereochemistry of the rings are 1H-NMR spectrum analysis and molecular modeling using both MM2 and MOPAC protocols of the Chem3D software [76], and also NOE-difference spectroscopy studies [100].
13C data reveals spiroisoxazoline ring systems have distinguished shifts. The difference between cyclohexadienone (G1, G2, G7, G8 and G9) and cyclohexenone (G3 and G4) systems are two chemical shifts at downfield for C-3’ and C-5’ (54–55) and one at upfield for C-2’ in G3 (56–61), and the same shifts for C-3, -3′, C-5, -5′, C-2, -2′ in G4 (56–61). The epoxide group in G5 and G6 can be characterized by the same shifts plus two differences: a strong shift at downfield for C-3 and C-3′ in G5 and C-3′ in G6. The other difference involves three chemical shifts at upfield for C-1, 1′, C-2, 2′ and C-6, 6′ of 62 and for C-1′, C-2′ and C-6′ of 63. Some 13C data as δ 67.2 and δ 65.7 attributed to chiral C-11 of compound 42 still remain with its stereochemistry unsolved [76].
According to Kossuga, 2004 [123], to determine the configuration of the relative stereochemistry of bis-oxazolidone uses [α] of (7R,11R) bis-oxazolidone with absolute stereochemistry [64]. It was possible to determine the relative configuration of bis-oxazolidones (7*R,11*S) and (11*R,7*S) isolated in previous works as can be seen in Table 2 [63,65,109].

4. Conclusions

The genus Aplysina is one of the richest in secondary metabolites, which have been cataloged in 14 species from the Aplysinidae family. Most classes of compounds mentioned here present themselves brominated, and, despite the large number of species of the genus Aplysina, many have not been studied chemically. The halogenated compounds found in marine sponges of this genus were classified into: (A) Bromotyramines, (B) Cavernicolins, (C) Hydroverongiaquinols, (D) Bromotyrosineketals, (E) Bromotyrosine Lactone derivatives, (F) Oxazolidones, (G) Spiroisoxazolines, (H) Verongiabenzenoids, (I) Verongiaquinols and (J) Dibromocyclohexadiens.
In view of their potential for producing new compounds of pharmacological interest, sponges have been one of the most studied organisms from a chemical point of view. Over the past 20 years, hundreds of substances have been isolated from sponges, many of which have been identified and show interesting biological and pharmacological activities, as for example, antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antituberculosis, antiviral, immunosuppressive and neurosuppressive activities.
The species of the genus Aplysina also show a wide structural variety of nitrogen compounds, present only in marine sponges. Therefore they are a rich source for research of new structural models for future therapeutic applications. With the information provided in this review, we hope to facilitate research in the field and to contribute to a better understanding and knowledge of the phytochemistry of this genus.

Acknowledgements

The authors thank the University of Illinois in Chicago, U.S.A., for the use of the NAPRALERT database for this study. Financial support was provided by CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico), PgPNSB (Pós-Graduação em Produtos Naturais e Sintéticos Bioativos), and PRONEX-FAPESQ-PB (Programa de Apoio a Núcleos de Excelência-Fundação de Apoio a Pesquisa do Estado da Paraíba).We also thank Mr. Raimundo Nonato da Silva Filho for technical help.

References

  1. Sponge. Available online: http://www.britannica.com (accessed on 5 October 2010).
  2. Hentschel, U.; Hopke, J.; Horn, M.; Friedrich, A.B.; Wagner, M.; Hacker, J.; Moore, B.S. Molecular evidence for a uniform microbial community in sponges from different oceans. Appl. Environ. Microbiol 2002, 68, 4431–4440. [Google Scholar]
  3. Radjasa, O.K.; Sabdono, A.; Junaidi, J.; Zocchi, E. Richness of secondary metabolite-producing marine bacteria associated with sponge Haliclona sp. Int. J. Pharmacol 2007, 3, 275–279. [Google Scholar]
  4. Thomas, T.R.A.; Kavlekar, D.P.; LokaBharathi, P.A. Marine drugs from sponge-microbe association-a review. Mar. Drugs 2010, 8, 1417–1468. [Google Scholar]
  5. Ebada, S.S.; Lin, W.; Proksch, P. Bioactive sesterterpenes and triterpenes from marine sponges: Occurrence and pharmacological significance. Mar. Drugs 2010, 8, 313–346. [Google Scholar]
  6. Andavan, G.S.B.; Lemmens-Gruber, R. Cyclodepsipeptides from marine sponges: Natural agents for drug research. Mar. Drugs 2010, 8, 810–834. [Google Scholar]
  7. Balan, V.; Nangia-Makker, P.; Raz, A. Galectins as cancer biomarkers. Cancers 2010, 2, 592–610. [Google Scholar]
  8. Exposito, J.-Y.; Valcourt, U.; Cluzel, C.; Lethias, C. The fibrillar collagen family. Int. J. Mol. Sci 2010, 11, 407–426. [Google Scholar]
  9. Longeon, A.; Copp, B.R.; Quévrain, E.; Roué, M.; Kientz, B.; Cresteil, T.; Petek, S.; Debitus, C.; Bourguet-Kondracki, M.-L. Bioactive indole derivatives from the south pacific marine sponges Rhopaloeides odorabile and Hyrtios sp. Mar. Drugs 2011, 9, 879–888. [Google Scholar]
  10. Lee, Y.K.; Lee, J.-H.; Lee, H.K. Microbial symbiosis in marine sponges. J. Microbiol 2001, 39, 254–264. [Google Scholar]
  11. Belarbi, E.H.; Gómez, A.C.; Chisti, Y.; Camacho, F.G.; Grima, E.M. Producing drugs from marine sponges. Biotechnol. Adv 2003, 21, 585–598. [Google Scholar]
  12. Fieseler, L.; Horn, M.; Wagner, M.; Hentschel, U. Discovery of the novel candidate phylum “Poribacteria” in marine sponges. Appl. Environ. Microbiol 2004, 70, 3724–3732. [Google Scholar]
  13. Thoms, C.; Ebel, R.; Proksch, P. Activated chemical defense in Aplysina sponges revisited. J. Chem. Ecol 2006, 32, 97–123. [Google Scholar]
  14. Thakur, N.L.; Müller, W.E.G. Biotechnological potential of marine sponges. Curr. Sci. India 2004, 86, 1506–1512. [Google Scholar]
  15. Erpenbeck, D.; van Soest, R. Status and perspective of sponge chemosystematics. Mar. Biotechnol 2007, 9, 2–19. [Google Scholar]
  16. Fusetani, N.; Matsunaga, S. Bioactive sponge peptides. Chem. Rev 1993, 93, 1793–1806. [Google Scholar]
  17. Sagar, S.; Kaur, M.; Minneman, K.P. Antiviral lead compounds from marine sponges. Mar. Drugs 2010, 8, 2619–2638. [Google Scholar]
  18. Koopmans, M.; Martens, D.; Wijffels, R. Towards commercial production of sponge medicines. Mar. Drugs 2009, 7, 787–802. [Google Scholar]
  19. Sepčić, K.; Kauferstein, S.; Mebs, D.; Turk, T. Biological activities of aqueous and organic extracts from tropical marine sponges. Mar. Drugs 2010, 8, 1550–1566. [Google Scholar]
  20. Esteves, A.I.S.; Nicolai, M.; Humanes, M.; Goncalves, J. Sulfated polysaccharides in marine sponges: Extraction methods and anti-HIV activity. Mar. Drugs 2011, 9, 139–153. [Google Scholar]
  21. Alvarez, B.; Crisp, M.D.; Driver, F.; Hooper, J.N.A.; van Soest, R.W.M. Phylogenetic relationships of the family Axinellidae (Porifera: Demospongiae) using morphological and molecular data. Zool. Scr 2000, 29, 169–198. [Google Scholar]
  22. Proksch, P.; Edrada, R.; Ebel, R. Drugs from the seas—Current status and microbiological implications. Appl. Microbiol. Biot 2002, 59, 125–134. [Google Scholar]
  23. Sipkema, D.; Franssen, M.; Osinga, R.; Tramper, J.; Wijffels, R. Marine sponges as pharmacy. Mar. Biotechnol 2005, 7, 142–162. [Google Scholar]
  24. Tymiak, A.A.; Rinehart, K.L., Jr; Bakus, G.J. Constituents of morphologically similar sponges: Aplysina and Smenospongia species. Tetrahedron 1985, 41, 1039–1047. [Google Scholar]
  25. Rinehart, K.L., Jr; Shaw, P.D.; Shield, L.S.; Gloer, J.B.; Harbour, G.C.; Koker, M.E.S.; Samain, D.; Schwartz, R.E.; Tymiak, A.A.; Weller, D.L.; et al. Marine natural products as sources of antiviral, antimicrobial and antineoplastic agents. Pure Appl. Chem 1981, 53, 795–817. [Google Scholar]
  26. Goo, Y.M. Antimicrobial and antineoplastic tyrosine metabolites from a marine sponge, Aplysina fistularis. Arch. Pharm. Res 1985, 8, 21–30. [Google Scholar]
  27. Capon, R.; Macleod, J. Two epimeric dibromo nitriles from the Australian sponge Aplysina laevis. Aust. J. Chem 1987, 40, 341–346. [Google Scholar]
  28. Ajabnoor, M.A.M.; Tilmisany, A.K.; Taha, A.M.; Antonius, A. Isolation of antibiotic principles from some red sea sponges. Egypt. J. Pharm. Sci 1991, 32, 797–815. [Google Scholar]
  29. Gunasekera, S.P.; Cross, S.S. Fistularin 3 and 11-ketofistularin 3. feline leukemia virus active bromotyrosine metabolites from the marine sponge Aplysina archeri. J. Nat. Prod 1992, 55, 509–512. [Google Scholar]
  30. Rodríguez, A.D.; Piña, I.C. The structures of aplysinamisines I, II, and III: New bromotyrosine-derived alkaloids from the Caribbean sponge Aplysina cauliformis. J. Nat. Prod 1993, 56, 907–914. [Google Scholar]
  31. Gopichand, Y.; Schmitz, F.J. Marine natural products: Fistularin-1, -2 and -3 from the sponge Aplysina fistularis forma fulva. Tetrahedron Lett 1979, 20, 3921–3924. [Google Scholar]
  32. Ajabnoor, M.A.M.; Tilmisany, A.K.; Taha, A.M.; Antonius, A. Effect of red sea sponge extracts on blood glucose levels in normal mice. J. Ethnopharmacol 1991, 33, 103–106. [Google Scholar]
  33. Pinheiro, U.S.; Hajdu, E.; Custódio, M.R. Aplysina nardo (Porifera, Verongida, Aplysinidae) from the Brazilian coast with description of eight new species. Zootaxa 2007, 1609, 1–51. [Google Scholar]
  34. Ciminiello, P.; Costantino, V.; Fattorusso, E.; Magno, S.; Mangoni, A.; Pansini, M. Chemistry of Verongida sponges, II. Constituents of the Caribbean sponge Aplysina fistularis forma fulva. J. Nat. Prod 1994, 57, 705–712. [Google Scholar]
  35. Pauletti, P.M.; Cintra, L.S.; Braguine, C.G.; Filho, A.A.S.; Silva, M.L.A.; Cunha, W.R.; Januário, A.H. Halogenated indole alkaloids from marine invertebrates. Mar. Drugs 2010, 8, 1526–1549. [Google Scholar]
  36. Aiello, A.; Fattorusso, E.; Imperatore, C.; Menna, M.; Müller, W. Iodocionin, a cytotoxic iodinated metabolite from the Mediterranean Ascidian Ciona edwardsii. Mar. Drugs 2010, 8, 285–291. [Google Scholar]
  37. Cabrita, M.T.; Vale, C.; Rauter, A.P. Halogenated compounds from marine algae. Mar. Drugs 2010, 8, 2301–2317. [Google Scholar]
  38. Vairappan, C.S.; Ishii, T.; Lee, T.K.; Suzuki, M.; Zhaoqi, Z. Antibacterial activities of a new brominated diterpene from Borneon Laurencia spp. Mar. Drugs 2010, 8, 1743–1749. [Google Scholar]
  39. La Barre, S.; Potin, P.; Leblanc, C.; Delage, L. The Halogenated metabolism of brown algae (Phaeophyta), its biological importance and its environmental significance. Mar. Drugs 2010, 8, 988–1010. [Google Scholar]
  40. Güven, K.C.; Percot, A.; Sezik, E. Alkaloids in marine algae. Mar. Drugs 2010, 8, 269–284. [Google Scholar]
  41. Genovese, G.; Tedone, L.; Hamann, M.; Morabito, M. The Mediterranean red alga Asparagopsis: A source of compounds against Leishmania. Mar. Drugs 2009, 7, 361–366. [Google Scholar]
  42. Matta, C.B.B.; Souza, E.T.; Queiroz, A.C.; Lira, D.P.; Araújo, M.V.; Cavalcante-Silva, L.H.A.; Miranda, G.E.C.; Araújo-Júnior, J.X.; Barbosa-Filho, J.M.; Santos, B.V.O.; et al. Antinociceptive and anti-inflammatory activity from algae of the genus Caulerpa. Mar. Drugs 2011, 9, 307–318. [Google Scholar]
  43. Almeida, C.L.F.; Falcão, H.S.; Lima, G.R.M.; Montenegro, C.A.; Lira, N.S.; Athayde-Filho, P.F.; Rodrigues, L.C.; Souza, M.F.V.; Barbosa-Filho, J.M.; Batista, L.M. Bioactivities from marine algae of the genus Gracilaria. Int. J. Mol. Sci 2011, 12, 4550–4573. [Google Scholar]
  44. Souza, E.T.; Lira, D.P.; Queiroz, A.C.; Silva, D.J.C.; Aquino, A.B.; Mella, E.A.C.; Lorenzo, V.P.; Miranda, G.E.C.; Araújo-Júnior, J.X.; Chaves, M.C.O.; et al. The Antinociceptive and anti-inflammatory activities of caulerpin, a bisindole alkaloid isolated from seaweeds of the genus Caulerpa. Mar. Drugs 2009, 7, 689–704. [Google Scholar]
  45. Queiroz, T.M.; Machado, N.T.; Furtado, F.F.; Oliveira-Filho, A.A.; Alustau, M.C.; Figueiredo, C.S.; Miranda, G.E.C.; Barbosa-Filho, J.M.; Braga, V.A.; Medeiros, I.A. Vasorelaxation induced byDictyota pulchella(Dictyotaceae), a brown alga, is mediated via inhibition of calcium influx in rats. Mar Drugs 2011, 9, 2075–2088. [Google Scholar]
  46. Lira, N.S.; Monte-Neto, R.L.; Marchi, J.G.B.; Lins, A.C.S.; Pinheiro, U.S.; Tavares, J.F.; Silva, M.S.; Cunha, E.V.L.; Braz Filho, R.; Santos, C.F.; et al. Aplysfistularine: A novel dibromotyrosine derivative isolated fromAplysina fistularis. Mar. Drugs 2011. submitted. [Google Scholar]
  47. Lúcio, A.S.S.C.; Almeida, J.R.G.S.; Barbosa-Filho, J.M.; Pita, J.C.L.R.; Castello Branco, M.V.S.; Diniz, M.F.F.M.; Agra, M.F.; Cunha, E.V.L.; Silva, M.S.; Tavares, J.F. Azaphenathrene alkaloids with antitumoral activity from Anaxagorea dolichocarpa Sprague & Sandwith (Annonaceae). Molecules 2011, 16, 7125–7131. [Google Scholar]
  48. Bitencourt, M.A.O.; Dantas, G.R.; Lira, D.P.; Barbosa-Filho, J.M.; Miranda, G.E.C.; Santos, B.V.O.; Souto, J.T. Aqueous and methanolic extracts of Caulerpa mexicana suppress cell migration and ear edema induced by inflammatory agents. Mar. Drugs 2011, 9, 1332–1345. [Google Scholar]
  49. Alves, J.S.; Castro, J.C.M.; Freire, M.O.; da-Cunha, E.V.L.; Barbosa-Filho, J.M.; Silva, M.S. Complete assignment of the 1H and 13C NMR spectra of four triterpenes of the ursane, artane, lupane and friedelane groups. Magn. Reson. Chem 2000, 38, 201–206. [Google Scholar]
  50. Andrade, N.C.; Cunha, E.V.L.; Silva, M.S.; Agra, M.F.; Barbosa-Filho, J.M. Terpenoids of the Annonaceae: Distribution and Compilation of 13C NMR Data. In Recent Research Developments in Phytochemistry; Pandalai, S.G., Ed.; Research Signpost: Kerala, India, 2003; Volume 7, pp. 1–85. [Google Scholar]
  51. Sena-Filho, J.G.; Duringer, J.; Maia, G.L.A.; Tavares, J.F.; Xavier, H.S.; Silva, M.S.; da-Cunha, E.V.L.; Barbosa-Filho, J.M. Ecdysteroids from Vitex species: Distribution and compilation of their 13C-NMR spectral data. Chem. Biodivers 2008, 5, 707–713. [Google Scholar]
  52. Oliveira, S.L.; Silva, M.S.; Tavares, J.F.; Sena-Filho, J.G.; Lucena, H.F.S.; Romero, M.A.V.; Barbosa-Filho, J.M. Tropane alkaloids from Erythroxylum genus: Distribution and compilation of 13C-NMR spectral data. Chem. Biodivers 2010, 7, 302–326. [Google Scholar]
  53. Almeida, R.N.; Navarro, D.S.; Barbosa-Filho, J.M. Plants with central analgesic activity. Phytomedicine 2001, 8, 310–322. [Google Scholar]
  54. Silva, J.S.; Moura, M.D.; Oliveira, R.A.G.; Diniz, M.F.F.; Barbosa-Filho, J.M. Natural product inhibitors of ovarian neoplasia. Phytomedicine 2003, 10, 221–232. [Google Scholar]
  55. Falcão, H.S.; Mariath, I.R.; Diniz, M.F.F.M.; Batista, L.M.; Barbosa-Filho, J.M. Plants of the American continent with antiulcer activity. Phytomedicine 2008, 15, 132–146. [Google Scholar]
  56. Sousa, F.C.F.; Melo, C.T.V.; Citó, M.C.O.; Félix, F.H.C.; Vasconcelos, S.M.M.; Fonteles, M.M.F.; Barbosa Filho, J.M.; Viana, G.S.B. Plantas medicinais e seus constituintes bioativos: Uma revisão da bioatividade e potenciais benefícios nos distúrbios da ansiedade em modelos animais. Rev. Bras. Farmacogn 2008, 18, 642–654. [Google Scholar]
  57. Falcão, H.S.; Leite, J.A.; Barbosa-Filho, J.M.; Athayde-Filho, P.F.; Chaves, M.C.O.; Moura, M.D.; Ferreira, A.L.; Almeida, A.B.A.; Souza-Brito, A.R.M.; Diniz, M.F.F.M.; et al. Gastric and duodenal antiulcer activity of alkaloids: A review. Molecules 2008, 13, 3198–3223. [Google Scholar]
  58. Mota, K.S.L.; Dias, G.E.N.; Pinto, M.E.F.; Luiz-Ferreira, A.; Souza-Brito, A.R.S.; Hiruma-Lima, C.A.; Barbosa-Filho, J.M.; Batista, L.M. Flavonoids with gastroprotective activity. Molecules 2009, 14, 979–1012. [Google Scholar]
  59. Mariath, I.R.; Falcão, H.S.; Barbosa-Filho, J.M.; Sousa, L.C.F.; Tomaz, A.C.A.; Batista, L.M.; Diniz, M.F.F.M.; Athayde-Filho, P.F.; Tavares, J.F.; Silva, M.S.; et al. Plants of the American continent with antimalarial activity. Rev. Bras. Farmacogn 2009, 19, 158–191. [Google Scholar]
  60. Ribeiro Filho, J.; Falcao, H.S.; Batista, L.M.; Barbosa-Filho, J.M.; Piuvezam, M.R. Effects of Plant Extracts on HIV-1 Protease. Curr. HIV Res 2010, 8, 531–544. [Google Scholar]
  61. Lima, G.R.M.; Montenegro, C.A.; Almeida, C.L.F.; Athayde-Filho, P.F.; Barbosa-Filho, J.M.; Batista, L.M. Database survey of anti-inflammatory plants in South America: A review. Int. J. Mol. Sci 2011, 12, 2692–2749. [Google Scholar]
  62. Silva, F.L.; Fischer, D.C.H.; Tavares, J.F.; Silva, M.S.; Athayde-Filho, P.F.; Barbosa-Filho, J.M. Compilation of secondary metabolites from Bidens pilosa L. Molecules 2011, 16, 1070–1102. [Google Scholar]
  63. Ciminiello, P.; Fattorusso, E.; Forino, M.; Magno, S.; Pansini, M. Chemistry of verongida sponges VIII-bromocompounds from the Mediterranean sponges Aplysina aerophoba and Aplysina cavernicola. Tetrahedron 1997, 53, 6565–6572. [Google Scholar]
  64. Norte, M.; Rodriguez, M.L.; Fernández, J.J.; Eguren, L.; Estrada, D.M. Aplysinadiene and (R,R) 5 [3,5-dibromo-4-[(2-oxo-5-oxazolidinyl)] methoxyphenyl]-2-oxazolidinone, two novel metabolites from Aplysina aerophoba Synthes. Tetrahedron 1988, 44, 4973–4980. [Google Scholar]
  65. Borders, D.B.; Morton, G.O.; Wetzel, E.R. Structure of a novel bromine compound isolated from a sponge. Tetrahedron Lett 1974, 15, 2709–2712. [Google Scholar]
  66. Fattorusso, E.; Minale, L.; Sodano, G. Aeroplysinin-1, a new bromo-compound fromAplysina aerophoba. J. Chem. Soc. Chem. Comm 1970, 751–752. [Google Scholar]
  67. Cimino, G.; De Rosa, S.; De Stefano, S.; Self, R.; Sodano, G. The bromo-compounds of the true sponge Verongia aerophoba. Tetrahedron Lett 1983, 24, 3029–3032. [Google Scholar]
  68. Gunasekera, M.; Gunasekera, S.P. Dihydroxyaerothionin and aerophobin 1. Two brominated tyrosine metabolites from the deep water marine sponge Verongula rigida. J. Nat. Prod 1989, 52, 753–756. [Google Scholar]
  69. Kelecom, A.; Kannengiesser, G.J. Chemical constituents of Verongia sponges, II—Struture of two dibrominated compounds isolated from the Mediterranean sponge Verongia aerophoba. Ann. Acad. Braz. Sci 1979, 51, 639–641. [Google Scholar]
  70. Fattorusso, E.; Minale, L.; Sodano, G. Aeroplysinin-1, an antibacterial bromo-compound from the spongeVerongia aerophoba. J. Chem. Soc. Perk. Trans. 1 1972, 16–18. [Google Scholar]
  71. Makarieva, T.N.; Stonik, V.A.; Alcolado, P.; Elyakov, Y.B. Comparative study of the halogenated tyrosine derivatives from Demospongiae (Porifera). Comp. Biochem. Phys. B 1981, 68, 481–484. [Google Scholar]
  72. Mancini, I.; Guella, G.; Laboute, P.; Debitus, C.; Pietra, F. Hemifistularin 3: A degraded peptide or biogenetic precursor? Isolation from a sponge of the order Verongida from the coral sea or generation from base treatment of 11-oxofistularin 3. J. Chem. Soc. Perk. Trans. 1 1993, 3121–3125. [Google Scholar]
  73. Ciminiello, P.; Dell’Aversano, C.; Fattorusso, E.; Magno, S. Archerine, a novel anti-histaminic bromotyrosine-derived compound from the Caribbean marine sponge Aplysina archeri. Eur. J. Org. Chem 2001, 2001, 55–60. [Google Scholar]
  74. Ciminiello, P.; Dell’Aversano, C.; Fattorusso, E.; Magno, S.; Carrano, L.; Pansini, M. Chemistry of Verongida sponges. VII bromocompounds from the Caribbean sponge Aplysina archeri. Tetrahedron 1996, 52, 9863–9868. [Google Scholar]
  75. Saeki, B.M.; Granato, A.C.; Berlinck, R.G.S.; Magalhães, A.; Schefer, A.B.; Ferreira, A.G.; Pinheiro, U.S.; Hajdu, E. Two unprecedented dibromotyrosine-derived alkaloids from the Brazilian endemic marine sponge Aplysina caissara. J. Nat. Prod 2002, 65, 796–799. [Google Scholar]
  76. Lira, T.O.; Berlinck, R.G.S.; Nascimento, G.G.F.; Hajdu, E. Further dibromotyrosine-derived metabolites from the marine sponge Aplysina caissara. J. Braz. Chem. Soc 2006, 17, 1233–1240. [Google Scholar]
  77. Rodríguez, A.D.; Akee, R.K.; Scheuer, P.J. Two bromotyrosine-cysteine derived metabolites from a sponge. Tetrahedron Lett 1987, 28, 4989–4992. [Google Scholar]
  78. Ciminiello, P.; Dell’Aversano, C.; Fattorusso, E.; Magno, S.; Pansini, M. Chemistry of Verongida sponges. 9. Secondary metabolite composition of the Caribbean sponge Aplysina cauliformis. J. Nat. Prod 1999, 62, 590–593. [Google Scholar]
  79. D’Ambrosio, M.; Guerriero, A.; Traldi, P.; Pietra, F. Cavernicolin-1 and cavernicolin-2, epimeric dibromolactams from the Mediterranean sponge Aplysina (Verongia) cavernicola. Tetrahedron Lett 1982, 23, 4403–4406. [Google Scholar]
  80. D’Ambrosio, M.; Guerriero, A.; de Clauser, R.; de Stanchina, G.; Pietra, F. Dichloroverongiaquinol, a new marine antibacterial compound from Aplysina cavernicola. Isolation and synthesis. Cell. Mol. Life Sci 1983, 39, 1091–1092. [Google Scholar]
  81. D’Ambrosio, M.; Guerriero, A.; Pietra, F. Novel, racemic or nearly-racemic antibacterial bromoand chloroquinols and γ-lactams of the verongiaquinol and the cavernicolin type from the marine sponge Aplysina (= Verongia) cavernicola. Helv. Chim. Acta 1984, 67, 1484–1492. [Google Scholar]
  82. D’Ambrosio, M.; Mealli, C.; Guerriero, A.; Pietra, F. 7-Bromocavernicolenone, a new α-bromoenone from the Mediterranean sponge Aplysina (=Verongia) cavernicola. Implied, unprecedented involvement of a halogenated dopa in the biogenesis of a natural product. Helv. Chim. Acta 1985, 68, 1453–1460. [Google Scholar]
  83. Pereira, F.R.; Marques, S.O.; Nascimento, A.M.; Gandolfi, R.C.; Hajdu, E.; Peixinho, S.; Custódio, M.R.; Berlinck, R.G.S. Metabólitos Derivados da Dibromotirosina das Esponjas Aplysina fulva, A. conulosa (sp. n.) and A. fistularis. In XXIX Reunião Anual da Sociedade Brasileira de Química; Sociedade Brasileira de Química: Águas de Lindóia, Brazil, 2006; p. 335. [Google Scholar]
  84. Xynas, R.; Capon, R.J. Two new bromotyrosine-derived metabolites from an Australian marine sponge, Aplysina sp. Aust. J. Chem 1989, 42, 1427–1433. [Google Scholar]
  85. Tymiak, A.A. Structure elucidation and biosynthesis of selected bioactive marine natural products. Dissert. Abs. Int. B 1985, 43, 3990–3991. [Google Scholar]
  86. Rinehart, K.L., Jr.; Johnson, R.D.; Paul, I.C.; McMillan, J.A.; Siuda, J.F.; Krejcarek, G.E. Identification of Compounds in Selected Marine Organisms by Gas Chromatography-Mass Spectrometry, Field Desorption Mass Spectrometry, and Other Physical Methods. In Food—Drugs from the Sea: Proceedings, 1974; Webber, H.H., Ruggieri, G.D., Eds.; Marine Technology Society: Columbia, MD, USA, 1976. [Google Scholar]
  87. Sharma, G.M.; Vig, B.; Burkholder, P.R. Antimicrobial substances of sponges. IV. Structure of a bromine-containing compound from a marine sponge. J. Org. Chem 1970, 35, 2823–2826. [Google Scholar]
  88. Gandolfi, R.C.; Medina, M.B.; Berlinck, R.G.S.; Lira, S.P.; Galetti, F.C.S.; Silva, C.L.; Veloso, K.; Ferreira, A.G.; Hajdu, E.; Peixinho, S. Metabólitos secundários das esponjas Aplysina fistularis e Dysidea sp. e atividade antituberculose da 11-cetofistularina-3. Quim. Nova 2010, 33, 1853–1858. [Google Scholar]
  89. Walker, R.P.; Thompson, J.E.; Faulkner, D.J. Exudation of biologically-active metabolites in the sponge Aplysina fistularis. II. Chemical evidence. Mar. Biol 1985, 88, 27–32. [Google Scholar]
  90. Kobayashi, J.I.; Tsuda, M.; Agemi, K.; Shigemori, H.; Ishibashi, M.; Sasaki, T.; Mikami, Y. Purealidins B and C, new bromotyrosine alkaloids from the Okinawan marine sponge Psammaplysilla purea. Tetrahedron 1991, 47, 6617–6622. [Google Scholar]
  91. Krejcarek, G.E.; White, R.H.; Hager, L.P.; McClure, W.O.; Johnson, R.D.; Rinehart, K.L.; McMillan, J.A.; Paul, I.C.; Shaw, P.D.; Brusca, R.C. A rearranged dibromotyrosine metabolite from Verongia aurea. Tetrahedron Lett 1975, 16, 507–510. [Google Scholar]
  92. Sharma, G.M.; Burkholder, P.R. Studies on antimicrobial substances of sponges. I. Isolation, purification, and properties of a new bromine-containing antibacterial substance. J. Antibiot 1967, 20, 200–203. [Google Scholar]
  93. Sharma, G.M.; Burkholder, P.R. Studies on the antimicrobial substances of sponges II. Structure and synthesis of a bromine-containing antibacterial, compound from a marine sponge. Tetrahedron Lett 1967, 8, 4147–4150. [Google Scholar]
  94. Minale, L. Natural product chemistry of the marine sponges. Pure Appl. Chem 1976, 48, 7–23. [Google Scholar]
  95. Minale, L.; Cimino, G.; de Stefano, S.; Sodano, G. Natural products from Porifera. Fortschr. Chem. Org. Naturst 1976, 33, 1–72. [Google Scholar]
  96. Carney, J.R.; Rinehart, K.L. Biosynthesis of brominated tyrosine metabolites by Aplysina fistularis. J. Nat. Prod 1995, 58, 971–985. [Google Scholar]
  97. Nuñez, C.V.; Almeida, E.V.R.; Granato, A.C.; Marques, S.O.; Santos, K.O.; Pereira, F.R.; Macedo, M.L.; Ferreira, A.G.; Hajdu, E.; Pinheiro, U.S.; et al. Chemical variability within the marine sponge Aplysina fulva. Biochem. Syst. Ecol 2008, 36, 283–296. [Google Scholar]
  98. Rogers, E.W.; Oliveira, M.F.; Berlinck, R.G.S.; König, G.M.; Molinski, T.F. Stereochemical heterogeneity in Verongid sponge metabolites. absolute stereochemistry of (+)-fistularin-3 and (+)-11-epi-fistularin-3 by microscale LCMS-Marfey’s analysis. J. Nat. Prod 2005, 68, 891–896. [Google Scholar]
  99. Rogers, E.W.; Molinski, T.F. Highly polar spiroisoxazolines from the sponge Aplysina fulva. J. Nat. Prod 2007, 70, 1191–1194. [Google Scholar]
  100. Encarnación, R.D.; Sandoval, E.; Malmstrøm, J.; Christophersen, C. Calafianin, a bromotyrosine derivative from the marine sponge Aplysina gerardogreeni. J. Nat. Prod 2000, 63, 874–875. [Google Scholar]
  101. Hernández-Guerrero, C.J.; Zubía, E.; Ortega, M.J.; Carballo, J.L. Cytotoxic dibromotyrosine-derived metabolites from the sponge Aplysina gerardogreeni. Bioorg. Med. Chem 2007, 15, 5275–5282. [Google Scholar]
  102. Fendert, T.; Wray, V.; van Soest, R.W.M.; Proksch, P. Bromoisoxazoline alkaloids from the Caribbean sponge Aplysina insularis. Z. Naturforsch 1999, 54c, 246–252. [Google Scholar]
  103. Compagnone, R.S.; Avila, R.; Suárez, A.I.; Abrams, O.V.; Rangel, H.R.; Arvelo, F.; Piña, I.C.; Merentes, E. 11-Deoxyfistularin-3, a new cytotoxic metabolite from the Caribbean sponge Aplysina fistularis insularis. J. Nat. Prod 1999, 62, 1443–1444. [Google Scholar]
  104. Acosta, A.L.; Rodríguez, A.D. 11-Oxoaerothionin: A cytotoxic antitumor bromotyrosine-derived alkaloid from the Caribbean marine sponge Aplysina lacunosa. J. Nat. Prod 1992, 55, 1007–1012. [Google Scholar]
  105. Evan, T.; Rudi, A.; Ilan, M.; Kashman, Y. Aplyzanzine A, a new dibromotyrosine derivative from a Verongida sponge. J. Nat. Prod 2001, 64, 226–227. [Google Scholar]
  106. Kossuga, M.H.; Lira, S.P.; Nascimento, A.M.; Gambardella, M.T.P.; Berlinck, R.G.S.; Torres, Y.R.; Nascimento, G.G.F.; Pimenta, E.F.; Silva, M.; Thiemann, O.H.; et al. Isolamento e atividades biológicas de produtos naturais das esponjas Monanchora arbuscula, Aplysina sp. Petromica ciocalyptoides e Topsentia ophiraphidites, da ascídia Didemnum ligulum e do octocoral Carijoa riisei. Quim. Nova 2007, 30, 1194–1202. [Google Scholar]
  107. Kashman, Y.; Groweiss, A.; Carmely, S.; Kinamoni, Z.; Czarkie, D.; Rotem, M. Recent research in marine natural products from the red sea. Pure Appl. Chem 1982, 54, 1995–2010. [Google Scholar]
  108. Ciminiello, P.; Dell’Aversano, C.; Fattorusso, E.; Magno, S.; Pansini, M. Chemistry of Verongida sponges. 10. Secondary metabolite composition of the Caribbean Sponge Verongula gigantea. J. Nat. Prod 2000, 63, 263–266. [Google Scholar]
  109. Cruz, F.; Quijano, L.; Gómez-Garibay, F.; Rios, T. Brominated metabolites from the sponge Aplysina (Verongia) thiona. J. Nat. Prod 1990, 53, 543–548. [Google Scholar]
  110. Ayanoglu, E.; Djerassi, C.; Erdman, T.R.; Scheuer, P.J. Minor and trace sterols in marine invertebrates V. isolation, structure elucidation and synthesis of 3[beta]-hydroxy-26,27-bisnorcholest-5-en-24-one from the sponge Psammaplysilla purpurea. Steroids 1978, 31, 815–822. [Google Scholar]
  111. Carballeira, N.M.; Bou, C.R. The sterol composition of the marine sponge Aplysina (=Verongia) archeri: A comparative study of the Verongidae. Comp. Biochem. Phys. B 1989, 93, 175–179. [Google Scholar]
  112. Hertzberg, S.; Bergquist, P.; Liaaen-Jensen, S. Further occurrence of sulphated carotenoids in Ianthella species (Desmospongia). Biochem. Syst. Ecol 1989, 17, 51–53. [Google Scholar]
  113. Nichols, S.A. An evaluation of support for order-level monophyly and interrelationships within the class Demospongiae using partial data from the large subunit rDNA and cytochrome oxidase subunit I. Mol. Phylogenet. Evol 2005, 34, 81–96. [Google Scholar]
  114. Lawson, M.; Thompson, J.; Djerassi, C. Localization of long-chain fatty acids and unconventional sterols in spherulous cells of a marine sponge. Lipids 1988, 23, 1037–1048. [Google Scholar]
  115. Ciminiello, P.; Fattorusso, E.; Magno, S.; Pansini, M. Chemistry of Verongida sponges VI. Comparison of the secondary metabolic composition of Aplysina insularis and Aplysina fulva. Biochem. Syst. Ecol 1996, 24, 105–113. [Google Scholar]
  116. Hamann, M.T.; Scheuer, P.J.; Kelly-Borges, M. Biogenetically diverse, bioactive constituents of a sponge, order Verongida: Bromotyramines and sesquiterpene-shikimate derived metabolites. J. Org. Chem 1993, 58, 6565–6569. [Google Scholar]
  117. D’Ambrosio, M.; Guerriero, A.; Pietra, F. N-Carbamoylpyrrolidine and 7-chlorocavernicolenone, two new metabolites of the Mediterranean sponge Aplysina (=Verongia) cavernicola. Comp. Biochem. Phys. B 1986, 83, 309–312. [Google Scholar]
  118. Cavazza, M.; Guella, G.; Nucci, L.; Pergola, F.; Bicchierini, N.; Pietra, F. Anodic oxidation of 3,5-dihalogenotyrosines as a model reaction for the biogenesis of the cavernicolins, metabolites of the Verongid spongeAplysina cavernicola. J. Chem. Soc. Perk. Trans. 1 1993, 3117–3120. [Google Scholar]
  119. Calcul, L.; Inman, W.D.; Morris, A.A.; Tenney, K.; Ratnam, J.; McKerrow, J.H.; Valeriote, F.A.; Crews, P. Additional insights on the bastadins: Isolation of analogues from the sponge Ianthella cf. reticulata and exploration of the oxime configurations. J. Nat. Prod 2010, 73, 365–372. [Google Scholar]
  120. Andersen, R.J.; Faulkner, D.J. A novel antibiotic from a sponge of the genus Verongia. Tetrahedron Lett 1973, 14, 1175–1178. [Google Scholar]
  121. Kasperek, G.J.; Bruice, T.C.; Yagi, H.; Kaubsich, N.; Jerina, D.M. Solvolytic chemistry of 1,4-dimethylbenzene oxide. A new and novel mechanism for the NIH shift. J. Am. Chem. Soc 1972, 94, 7876–7882. [Google Scholar]
  122. Huang, X.-P.; Deng, Z.-W.; van Soest, R.W.M.; Lin, W.-H. Brominated derivatives from the Chinese sponge Pseudoceratina sp. J. Asian Nat. Prod. Res 2008, 10, 239–242. [Google Scholar]
  123. Kossuga, M.H.; MacMillan, J.B.; Rogers, E.W.; Molinski, T.F.; Nascimento, G.G.F.; Rocha, R.M.; Berlinck, R.G.S. (2S,3R)-2-Aminododecan-3-ol, a new antifungal agent from the Ascidian Clavelina oblonga. J. Nat. Prod 2004, 67, 1879–1881. [Google Scholar]
  124. Peng, J.; Li, J.; Hamann, M.T. The Marine Bromotyrosine Derivatives. In The Alkaloids: Chemistry and Biology; Cordell, G.A., Ed.; Academic Press: Gulf Breeze, FL, USA, 2005; Volume 61, p. 59. [Google Scholar]
  125. Aiello, A.; Fattorusso, E.; Menna, M.; Pansini, M. Chemistry of Verongida sponges—V. Brominated metabolites from the Caribbean sponge Pseudoceratina sp. Biochem. Syst. Ecol 1995, 23, 377–381. [Google Scholar]
  126. Moody, K.; Thomson, R.H.; Fattorusso, E.; Minale, L.; Sodano, G. Aerothionin and homoaerothionin: Two tetrabromo spirocyclohexadienylisoxazoles from Verongia sponges. J. Chem. Soc. Perk. Trans 1 1972, 1, 18–24. [Google Scholar]
  127. Bergquist, P.R. Sponges; University of California Press: Berkeley and Los Angeles, CA, USA, 1978. [Google Scholar]
  128. Teeyapant, R.; Proksch, P. Biotransformation of brominated compounds in the marine sponge Verongia aerophoba—Evidence for an induced chemical defense? Naturwissenschaften 1993, 80, 369–370. [Google Scholar]
  129. Ebel, R.; Brenzinger, M.; Kunze, A.; Gross, H.J.; Proksch, P. Wound Activation of protoxins in marine sponge Aplysina aerophoba. J. Chem. Ecol 1997, 23, 1451–1462. [Google Scholar]
  130. Puyana, M.; Fenical, W.; Pawlik, J.R. Are there activated chemical defenses in sponges of the genus Aplysina from the Caribbean? Mar. Ecol. Prog. Ser 2003, 246, 127–135. [Google Scholar]
  131. Weiss, B.; Ebel, R.; Elbrächter, M.; Kirchner, M.; Proksch, P. Defense metabolites from the marine sponge Verongia aerophoba. Biochem. Syst. Ecol 1996, 24, 1–7. [Google Scholar]
  132. Koulman, A.; Proksch, P.; Ebel, R.; Beekman, A.C.; van Uden, W.; Konings, A.W.T.; Pedersen, J.A.; Pras, N.; Woerdenbag, H.J. Cytoxicity and mode of action of aeroplysinin-1 and a related dienone from the sponge Aplysina aerophoba. J. Nat. Prod 1996, 59, 591–594. [Google Scholar]
  133. Nagaraja, K.V.; Shaw, P.D. Inhibition of wheat germ RNA polymerase II by 2,6-dibromobenzoquinone and related compounds from Aplysina fistularis. Arch. Biochem. Biophys 1982, 215, 544–550. [Google Scholar]
  134. Chang, C.W.J.; Weinheimer, A.J. 2-Hydroxy, 3,5-dibromo, 4-methoxyphenylacetamide. a dibromotyrosine metabolite from Psammopilla purpurea. Tetrahedron Lett 1977, 18, 4005–4007. [Google Scholar]
  135. Fulmor, W.; Van Lear, G.E.; Morton, G.O.; Mills, R.D. Isolation and absolute configuration of the aeroplysinin I enantiomorphic pair from Ianthella ardis. Tetrahedron Lett 1970, 11, 4551–4552. [Google Scholar]
  136. Gutiérrez, M.; Capson, T.L.; Guzmán, H.M.; González, J.; Ortega-Barría, E.; Quiñoá, E.; Riguera, R. Antiprotozoal activity against Plasmodium falciparum and Trypanosoma cruzi of aeroplysinin-1 isolated from the new sponge Aplysina chiriquensis. Pharm. Biol 2005, 43, 762–765. [Google Scholar]
  137. Córdoba, R.; Tormo, N.S.; Medarde, A.F.; Plumet, J. Antiangiogenic versus cytotoxic activity in analogues of aeroplysinin-1. Bioorg. Med. Chem 2007, 15, 5300–5315. [Google Scholar]
  138. Simões, C.M.O.; Petrovick, P.R. Farmacognosia: Da Planta ao Medicamento, 6 ed; Editora da UFSC: Santa Catarina, Brasil, 2010. [Google Scholar]
Marinedrugs 09 02316f1 1024
Figure 1. Metabolism of the bromotyrosine derived metabolites ( For the steps clarified in previous studies and For the biogenesis hypothesis).
Figure 1. Metabolism of the bromotyrosine derived metabolites ( For the steps clarified in previous studies and For the biogenesis hypothesis).
Marinedrugs 09 02316f1
Marinedrugs 09 02316f2 1024
Figure 2. Spiroisoxazoline and acetal formation as production artefacts.
Figure 2. Spiroisoxazoline and acetal formation as production artefacts.
Marinedrugs 09 02316f2
Table
Table 1. Bioactivities of marine sponges of the Aplysina genus.
Table 1. Bioactivities of marine sponges of the Aplysina genus.
Activity/Species NameType of ExtractBioassays Models, Organism, Dose or Route of AdministrationResultRef.
Antibacterial activity
Aplysina archeriMeOH Ext.Agar plate-Bacillus subtilis; Escherichia coli-1.0 mg/DiscActive[24]
Aplysina fistularisMeOH Ext.Agar plate-Bacillus subtilis; Escherichia coliActive[25]
MeOH-TolueneAgar plate-Bacillus subtilis; Escherichia coliActive[26]
Chromatographic FractionAgar plate-Staphylococcus aureus; Sarcinalutea; Klebsiella pneumonia; Proteus vulgaris; Bacteroides fragilis; Clostridium perfringens; Mycobacterium aviunActive[26]
Aplysina lacunosaMeOH Ext.Agar plate-Bacillus subtilis; Escherichia coliActive[25]
MeOH Ext.Agar plate-Bacillus subtilis; Escherichia coli-1.0 mg/DiscActive[24]
Aplysina laevisAcetone Ext.Agar plate-Bacillus subtilis; Escherichia coliActive[27]
Aplysina mollisEther Ext.Agar plate-Staphylococcus aureus-0.2μL/DiscActive[28]
Ether Ext.Agar plate-Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
CHCl3 Ext.Agar plate-Staphylococcus aureus-0.2 μL/DiscActive[28]
CHCl3 Ext.Agar plate-Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
Acetone Ext.Agar plate-Staphylococcus aureus-0.2 μL/DiscInactive[28]
ETOH (95%) Ext.Agar plate-Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
Benzene Ext.Agar plate-Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
Aplysina speciesEther Ext.Agar plate-Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
Acetone Ext.Agar plate-Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
ETOH (95%) Ext.Agar plate-Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
Antibacterial activityBenzene Ext.Agar plate-Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
Aplysina speciesCHCl3 Ext.Agar plate-Staphylococcus aureus; Escherichia coli; Pseudomonas aeruginosa-0.2 μL/DiscInactive[28]
Antiyeast activity
Aplysina archeriMeOH Ext.Agar plate-Saccharomyces cerevisiae-1.0 mg/DiscInactive[24]
Aplysina lacunosaMeOH Ext.Agar plate-Saccharomyces cerevisiae-1.0 mg/DiscWeak[24]
Activity
Antifungal activity
Aplysina archeriMeOH Ext.Agar plate-Penicillium atrovenetum-1.0 mg/DiscInactive[24]
Aplysina lacunosaMeOH Ext.Agar plate-Penicillium atrovenetum-1.0 mg/DiscInactive[24]
Antiviral activity
Aplysina archeriMeOH-TolueneCell culture-Virus-Feline LeukemiaActive[29]
Cytotoxic activity
Aplysina cauliformisCHCl3-MeOH Ext. (1:1)Cell culture-Cells-Cho K-1Active[30]
Aplysina fistularisMeOH Ext.Cell culture-Leuk L-1210-ED50 50 mcg/mLActive[25]
MeOH-TolueneCell culture-CA-9KBActive[26]
Chromatographic FractionCell culture-Leuk L-1210-IC50 0.14 mcg/mLActive[26]
Aplysina fulvaIsopropanol Ext.Cell culture-CA-9KB < ED50 20 mcg/mLActive[31]
Isopropanol Ext.Cell culture-Leuk L-1210 < ED50 20 mcg/mLActive[31]
Isopropanol Ext.Cell culture-Leuk P-388 < ED50 20 mcg/mLActive[31]
Aplysina lacunosaMeOH Ext.Cell culture-Leuk L-1210-ED50 8.2 mcg/mLInactive[25]
Hyperglycemic activity
Aplysina mollisETOH (95%) Ext.Mouse-Intragastric-Dose 200 mg/kgActive[32]
Table
Table 2. Distribution of the halogenated substances in the genus Aplysina.
Table 2. Distribution of the halogenated substances in the genus Aplysina.
SpeciesHalogenated SubstancesSubstance CodeNucleusRef.
A. aerophoba (Schmidt, 1862)Aeroplysinine 225E1[63]
Aplysinadiene26E1[64]
(7S*,11R*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone29F1[65]
(R,R)-5[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)] methoxyphenyl]-2-oxazolidone31F1[64]
Aerothionin41G1[34]
Homoaerothionin47G2[66]
Isofistularin-348G2[67]
Aerophobin-176G7[68]
2-(3,5-Dibromo-2-hydroxy-4-methoxyphenyl) acetamide84H[69]
3,5-Dibromo-4-methoxyphenol85H[64]
Methyl 2-(3,5-dibromo-2-hydroxy-4-methoxyphenyl) acetate86H[69]
Dibromoverongiaquinol or dienone or 3-5-dibromo-1-hydroxy-4-oxocyclohexa-2-5-diene-1-acetamide94I1[64]
Aeroplysinin 1100J[66,70]
A. archeri (Higgin, 1875)(7S*,11R*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone29F1[71]
11,19-Dideoxyfistularin 333G1[72]
Archerine43G1[73]
Fistularin-346G2[29]
11-Ketofistularin 351G2[29]
Aplysina compound 1 or 1-Oxa-2-azaspiro[4,5]deca-2,6-diene-3-carboxamide, N,N′-(2-oxo-1,4-butanediyl)bis[7,9-dibromo-10-hydroxy-8-oxo, [5R-[5α(5′R*,9′R*,10′S*),9α,10β]]-(9CI)57G4[74]
Aeroplysinin 1100J[74]
(+) Aeroplysinin 1100J[71]
(−) Aeroplysinin 1100J[71]
A. caissara (Pinheiro & Hajdu, 2001)2-(3,5-Dibromo-4,4-dimethoxy-1-hydroxy-2,5-cyclohexadien-1-yl) acetamide21D1[75]
Caissarine C42G1[76]
Caissarine B53G2[75]
Agelocaissarine A158G4[76]
Agelocaissarine A259G4[76]
Agelocaissarine B160G4[76]
Agelocaissarine B261G4[76]
Caissarine A79G8[75]
A. cauliformis (Carter, 1882)2-(3,5-Dibromo-1-hydroxy-4,4-dimethoxycyclohexa-2,5-dienyl)acetamide21D1[71]
(7S*,11R*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone29F1[71]
11-Oxoaerothionin52G2[77]
Aplysinametabolite or Methyl 4-((5S,10R)-7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro-[4.5]deca-2,6,8-trienecarboxamido)-2-oxobutylcarbamate64G7[78]
Methyl 4-((5S,10R)-7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro-[4.5]deca-2,6,8-trienecarboxamido)-3-oxobutylcarbamate or Aplysina compound 1365G7[78]
Methyl-4-((5S,10R)-7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-trienecarboxamido)butylcarbamate or Aplysina metabolite 1466G7[78]
Aplysinamisine-167G7[30]
Aplysinamisine-268G7[30]
Aplysinamisine-369G7[30]
Aeroplysinin 1100J[78]
A. cavernicola (Vacelet, 1959)Cavernicolin-15B1[79,80]
5-Bromo-7α-chlorocavernicolin7B2[81]
5-Bromo-7β-chlorocavernicolin8B2[81]
7β-Bromo-5-chlorocavernicolin9B2[81]
7α-Bromo-5-chlorocavernicolin10B2[81]
Monobromocavernicolin or 5-Bromocavernicolin11B2[81]
5-Chlorocavernicolin12B2[81,82]
7-Bromocavernicolenone13B3[82]
7-Chlorocavernicolenone14B3[63]
2-(3,5-Dibromo-1-hydroxy-4,4-dimethoxycyclohexa-2,5-dienyl) acetamide21D1[63]
Aeroplysinine 225E1[63]
11,19-Dideoxyfistularin 333G1[63]
12(R)-Hydroxy-11-oxoaerothionin36G1[63]
Aerothionin41G1[63]
Oxohomoaerothionin44G1[63]
11-Deoxyfistularin-345G2[63]
Homoaerothionin47G2[63]
Isofistularin348G2[63]
11-Oxoaerothionin52G2[63]
(+) 3-Bromo-5-chloroverongiaquinol or (+)-3-Bromo-5-chloro-1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetamide91I1[81]
(+) 3-Bromoverongiaquinol or (+)-3-Bromo-1-hydroxy-4-oxo-2,5-cyclohexadiene-1-acetamide92I1[81]
(DL) 5-Bromoverongiaquinol93I1[81]
Dichloroverongiaquinol95I1[80]
Aeroplysinin 1100J[63]
A. conulosa (Pulitzer-Finali, 1986)Aeroplysinine 225E1[83]
A. fistularis (Pallas, 1766)Aplysamine11A[84]
Aplysamine22A[84]
Aplysfistularine4A[46]
5-Amino-2,6-dichloro-4-hydroxycyclohex-2-enone acetic acid lactam15B4[26]
5-Amino-2-bromo-6-chloro-4-hydroxy-cyclohex-2-enone acetic acid lactam (5-bromo-7-chlorocavernicolin)16B4[26]
5-Amino-2-6-dibromo-4-hydroxy-cyclohex-2-enone acetic acid lactam or Cavernicolin17B4[26]
4,6-Dibromohomogentisamide18C[85]
3,5-Dibromohydroquinone-2-acetamide19C[86]
2-(3,5-Dibromo-1-hydroxy-4,4-dimethoxycyclohexa-2,5-dienyl) acetamide21D1[87]
Aeroplysinine 225E1[88]
(7S*,11R*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone29F1[71]
Aerothionin41G1[88,89]
Fistularin-346G2[88]
Homoaerothionin47G2[89]
11-Oxoaerothionin52G2[88]
Purealidin-L78G7[90]
2-(3,5-Dibromo-2-hydroxy-4-methoxyphenyl) acetamide84H[26,69]
2,6-Dibromo-1,4-benzoquinone87I1[91]
2,6-Dichloro-4-hydroxycyclohexa-2-5-dienone-4-acetamide89I1[26]
2-Bromo-6-chloro-4-hydroxycyclohexa-2,5-dienone-4-acetamide90I1[26]
Dibromoverongiaquinol or dienone or 3-5-dibromo-1-hydroxy-4-oxocyclohexa-2-5-diene-1-acetamide94I1[61–65,92–96]
Aeroplysinin 1100J[96]
A. fulva (Pallas, 1766)Cavernicolin-15B1[83,97]
Cavernicolin-26B1[83,97]
3,5-Dibromohydroquinone-2-acetamide19C[34]
2’-(3,5-Dibromo-4-hydroxyphenyl) acetamide20C[97]
2-(3,5-Dibromo-1-hydroxy-4,4-dimethoxycyclohexa-2,5-dienyl) acetamide21D1[97]
Aeroplysinine 225E1[34]
(7S*,11R*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone29F1[97]
11-Epi-fistularin-334G1[98]
11-Hydroxyfistularin-335G1[99]
12(R)-Hydroxy-11-oxoaerothionine36G1[34]
12(S)-Hydroxy-11-oxoaerothionine37G1[34]
Aerothionin41G1[34,83,97]
Fistularin-346G2[31,34,83,97]
Homoaerothionin47G2[34]
11-Hydroxyaerothionin50G2[34,97]
11-Oxoaerothionin52G2[34,97]
Aplysinamisine-167G7[97]
AraplysillinN9-sulfamate70G7[99]
Fistularin-172G7[34]
Fistularin-273G7[31]
N-[5S,10R)-7,9-Dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-triene-3-carboxy]-4-aminobutanoic acid74G7[99]
Aerophobin-176G7[97]
Aerophobin-277G7[97]
Aeroplysinin 1100J[34,66]
Aplysinafulvin101J[97]
A. gerardogreeni (Gomes & Bakus, 1992)Aerothionin41G1[100]
Homoaerothionin47G2[101]
Aplysinone A54G3[101]
Aplysinone D55G3[101]
Aplysinone B56G4[101]
Calafianin62G5[100]
Aplysinone C63G6[101]
2-(3,5-dibromo-2-hydroxy-4-methoxyphenyl) acetic acid83H[100]
A. insularis (Duchassaing & Michelotti, 1864)5-((2,6-Dibromo-4-(2-oxooxazolidin-5-yl)-phenoxy)-methyl)-5-methoxyoxazolidin-2-one32F3[74]
11,19-Dideoxyfistularin 333G1[102]
Aerothionin41G1[74,103]
Fistularin-346G2[74,102,103]
Homoaerothionin47G2[103]
11-Dihydroaerothionin49G2[102]
11-Oxoaerothionin52G2[102,103]
Aplysina metabolite 1466G7[74]
14-Oxoaerophobin-275G7[102]
Aerophobin-176G7[102]
Aerophobin-277G7[102]
(5S,10R)-Methyl 7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-triene-3-carboxylate80G9[102]
2-(3-Dibromo-4-hydroxyphenyl)-N,N,N-trimethylethanaminium82H[102]
A. lacunose (Lamarck, 1814)(7S*,11R*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone29F1[65]
(7R*,11S*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone30F2[71]
11,19-Dideoxyfistularin-333G1[104]
Aerothionin41G1[104]
Fistularin-346G2[104]
11-Hydroxyaerothionin50G2[104]
11-Oxoaerothionin52G2[104]
A. laevis (Carter, 1885)(1′R,5′R,6′S)-2-(3′,5′-Dibromo-1′,6′-dihydroxy-4′-oxo-cyclohex-2′-enyl) acetonitrile98I2[27]
(1′R,5’S,6′S)-2-(3′,5′-Dibromo-1′,6′-dihydroxy-4′-oxo-cyclohex-2′-enyl) acetonitrile99I2[27]
(+) Aeroplysinin 1100J[27]
A. speciesAplysamine11A[84]
Aplysamine22A[84]
Aplyzanzine A3A[105]
2-(3,5-Dibromo-4-ethoxy-1-hydroxy-4-methoxy-2,5-cyclohexadien-1-yl)-ethanamide22D2[71,84,106]
Aeroplysinine 225E1[106]
(7R*,11S*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidinone30F2[71]
(R,R)-5[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]methoxyphenyl]-2-oxazolidone31F1[106]
11,19-Dideoxyfistularin-333G1[72]
11-Oxofistularin-338G1[72]
19-Deoxy-11-oxofistularin39G1[72]
19-Deoxyfistularin-340G1[72]
Aerothionin41G1[107]
Hemifistularin-371G7[72]
(10R)-Ethyl-7,9-dibromo-10-hydroxy-8-methyl-1-oxa-2-azaspiro[4.5]deca-2,6,8-triene-3-carboxylate81G9[106]
2-(3-Bromo-4-hydroxyphenyl)-N,N,N-trimethylethanaminium82H[108]
A. thiona (Laubenfels, 1950)Aplysinketal A23D1[109]
Aplysinketal B24D1[109]
Aplysinolide27E2[109]
Aplysinimine28E2[109]
(7R*,11S*)-5-[3,5-Dibromo-4-[(2-oxo-5-oxazolidinyl)]-methoxyphenyl]-2-oxazolidinone30F2[109]
Aerothionin41G1[109]
Homoaerothionin47G2[109]
2-(3,5-Dibromo-2-hydroxy-4-methoxyphenyl)-acetamide84H[109]
2,6-Dibromo-4-acetamide-4-hydroxycyclohexadienone88I1[109]
Aplysina hydroxydienone or Dibromo compound 1096I1[109]
Aplysina hydroxydienoic methyl esther97I1[109]
Table
Table 3. Basic skeletons of the halogenated substances isolated from sponges of the Aplysina.
Table 3. Basic skeletons of the halogenated substances isolated from sponges of the Aplysina.
Marinedrugs 09 02316f3d
Table
Table 4. Substituent groups of the halogenated substances.
Table 4. Substituent groups of the halogenated substances.
Marinedrugs 09 02316f4g
Table
Table 5. Halogenated substances found in the genus Aplysina.
Table 5. Halogenated substances found in the genus Aplysina.
Halogen CompoundR1R2R3R4R5R6R7R8R9Nucleus
1MeMe-------A
2H(E) BrMeOPhCH2CNOHCO--------A
3HBr2MeOPhCH2CHN(CH3)2CO--------A
4MeMeMe------A
5BrHBr------B1
6HBrBr------B1
7ClHBr------B2
8HClBr------B2
9BrHCl------B2
10HBrCl------B2
11HHBr------B2
12HHCl------B2
13Br--------B3
14Cl--------B3
15HClCl------B4
16HClBr------B4
17HBrBr------B4
18OHHBrOHBr----C
19BrOHBrHOH----C
20HBrOHBrH----C
21MeMe-------D1
22EtMe-------D2
23MeButyl-------D1
24MePentyl-------D1
25MeOOHH------E1
26HBr(E) CH2=CH=CH=CH-OHBr----E1
27BrOMeMarinedrugs 09 02316f5BrH----E2
28BrOMeHBrH----E2
29-CH2(R)oxz--------F1
30-CH2(S)oxz--------F2
31-CH2(R)oxz--------F1
32-CH2MeOoxz--------F3
33-(CH2)3OBr2Ph(CH2)2---------G1
34-CH2(R)CHOHCH2OBr2PhCHOHCH2---------G1
35-(CH2)3OBr2Ph(R)CHOHCH2---------G1
36Marinedrugs 09 02316f6--------G1
37Marinedrugs 09 02316f7--------G1
38Marinedrugs 09 02316f8--------G1
39Marinedrugs 09 02316f9--------G1
40-CH2CHOHCH2OBr2Ph(CH2)2---------G1
41-(CH2)4---------G1
42-CH2CHOH(CH2)3---------G1
43-(CH2)2CH(imz)2(CH2)3---------G1
44Marinedrugs 09 02316f10--------G1
45-(CH2)3OBr2PhCHOHCH2---------G2
46-CH2(S)CHOHCH2OBr2PhCHOHCH2---------G2
47-(CH2)5---------G2
48-CH2CHOHCH2OBr2PhCHOHCH2---------G2
49-CH2(CHOH)2CH2---------G2
50-CH2CHOH(CH)2---------G2
51Marinedrugs 09 02316f11--------G2
52-CH2CH2O(CH2)2---------G2
53-(CH2)5COHCH2---------G2
54-(CH2)5---------G3
55-(CH2)4---------G3
56-(CH2)5-HBrOHHBrHHOHG4
57-CH2CH2O(CH2)2-BrHHOHHBrOHHG4
58-CH2CHOH(CH)2-HBrOHHBrHHOHG4
59-CH2CHOH(CH)2-BrHOHHHBrHOHG4
60-CH2CHOH(CH2)3-HBrOHHBrHHOHG4
61-CH2CHOH(CH2)3-BrHOHHHBrHOHG4
62-(CH2)4---------G5
63-(CH2)5---------G6
64Marinedrugs 09 02316f12--------G7
65Marinedrugs 09 02316f13--------G7
66Marinedrugs 09 02316f14--------G7
67-CH2(Z)(CH)2imzNH2--------G7
68-(CH2)5gnd--------G7
69-(CH2)3OBr2PhCHOHCH2NHAc--------G7
70-(CH2)3OBr2Ph(CH2)2NHSO3Na--------G7
71-CH2CHOHBr2PhOH--------G7
72-(CH2)3OBr2Phoxz--------G7
73-CH2Br2PhOoxz--------G7
74Marinedrugs 09 02316f15--------G7
75-(CH2)3imzONH2--------G7
76-(CH2)2imz--------G7
77-(CH2)3imzNH2--------G7
78-(CH2)4gnd--------G7
79-CH2CHOH(CH2)2gnd--------G8
80Me--------G9
81Et--------G9
82-(CH2)2N(Me)3H-------H
83Marinedrugs 09 02316f16OH-------H
84Marinedrugs 09 02316f17OH-------H
85OHH-------H
86Marinedrugs 09 02316f18OH-------H
87BrHHOBr----I1
88BrHOHMarinedrugs 09 02316f19Br----I1
89ClHOHMarinedrugs 09 02316f20Cl----I1
90BrHOHMarinedrugs 09 02316f21Cl----I1
91BrOHOHMarinedrugs 09 02316f22Cl----I1
92BrOHOHMarinedrugs 09 02316f23H----I1
93HOHOHMarinedrugs 09 02316f24Br----I1
94BrHOHMarinedrugs 09 02316f25Br----I1
95ClHOHMarinedrugs 09 02316f26Cl----I1
96BrHOHMarinedrugs 09 02316f27Br----I1
97BrHOCH2CH2OCH3Br----I1
98OHOH-------I2
99OHOH-------I2
100OHOHCH2CN------J
101MeOOHCH2CONH2------J
gnd = Guanidine; imz = Imidazole; oxz = Oxazolidinone.
Table
Table 6. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Bromotyramines.
Table 6. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Bromotyramines.
Position1234
1140.3140.3137.94138.58
2134.4134.4132.78132.80
3118.7118.7117.74118.02
4152.1152.1150.87151.30
5118.7118.7117.74118.02
6134.4134.4132.78132.80
735.235.234.2032.26
841.341.339.8160.20
9-165.8170.82-
10-152.969.84-
11-28.731.57-
12-113.1137.66-
13-134.7133.21-
14-130.3117.58-
15-155.8152.34-
16-112.1117.58-
17-131.7133.21-
1’71.771.769.7171.00
2’26.426.425.3826.79
3’56.956.955.4155.77
MeO-56.760.39-
+N(Me)243.7/43.643.741.51/42.9244.06
+N(Me)3---44.74
Table
Table 7. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Cavernicolins.
Table 7. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Cavernicolins.
Position56911121314
1184.0184.0183.4188.91188.8980.9082.7
256.953.158.039.7840.08--
368.764.767.958.6058.56168.30171.4
476.675.774.474.1573.4143.144.0
5149.9149.0146.3150.07145.8469.569.5
6120.8120.8127.4122.45130.18156.90153.2
743.045.142.443.5843.78118.80129.5
8173.9173.9173.6172.65172.72187.8188.9
9-----46.647.6
Table
Table 8. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Hydroverongiaquinols.
Table 8. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Hydroverongiaquinols.
Position20
1130.0
2133.0
3111.0
4150.0
5111.0
6133.0
2’40.0
3’173.4
Table
Table 9. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Bromotyrosineketals.
Table 9. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Bromotyrosineketals.
Position2223
171.3123.55
2140.3123.55
3124.1142.11
496.771.92
5124.1142.11
6140.3123.55
744.245.03
8173.2172.99
951.351.04
1060.263.98
1115.432.34
12-20.04
13-14.10
14--
Table
Table 10. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Bromotyrosine Lactone Derivatives.
Table 10. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Bromotyrosine Lactone Derivatives.
Position25262728
189.1148.85154.29161.3
2135.5109.12100.74106.7
3119.3103.75161.97155.2
4151.2147.16111.80110.8
5107.6103.75125.75135.2
677.0113.68122.35117.0
742.2146.35117.5340.6
8173.7165.91165.23164.0
9-144.60--
10-128.12150.75-
11-128.1225.21-
12-19.7923.69-
MeO61.5-61.060.8
Table
Table 11. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Oxazolides.
Table 11. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Oxazolides.
Position29303132
1153.5151.6142.3140.45
2119.3117.6118.2118.63
3131.9130.7130.8131.45
4140.6138.9140.0152.60
5131.9130.7130.8131.45
6119.3117.6142.3118.63
776.374.354.375.78
847.946.947.048.42
9159.8158.5 or 158.2157.8159.05
1075.073.053.072.05
1175.573.553.55
1241.741.141.4746.97
13160.2161.35158.4161.35
MeO---50.25
Table
Table 12. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Spiroisoxazolines.
Table 12. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Spiroisoxazolines.
Position333435363738394041
175.2875.075.4275.4775.4775.2975.1175.0975.5
2122.07122.0122.74114.14114.14122.11122.11122.10114.2
3148.77148.6149.28149.28149.28148.82148.73148.75149.3
4113.81113.7114.16122.78122.78113.85113.85113.78122.7
5132.37132.0132.24132.23132.23132.24132.27132.28133.2
691.6791.892.4892.6492.6490.0491.9591.5692.6
740.1339.840.1340.0940.0939.9939.8740.0340.1
8155.24154.9155.27155.12155.12154.80154.79155.14155.5
9160.07160.4161.81161.93161.93160.29160.24160.00161.6
1′75.2875.175.4275.4775.4775.2975.1875.2075.5
2′122.07122.1122.74114.14114.14122.11122.11122.10114.2
3′148.77148.6149.28149.28149.28148.82148.74148.75149.3
4′113.81113.7114.16122.78122.78113.85113.85113.78122.7
5′132.30132.1132.16133.21133.21132.23132.28132.28133.2
6′91.6791.892.4892.5492.5491.8691.5991.7692.6
7′40.0939.940.0440.0340.0339.8940.0940.0840.1
8′155.14155.0154.12154.92154.92155.16155.16155.16155.5
9′160.01160.5161.55161.80161.80160.48160.03160.41161.6
1037.4743.437.9449.8749.8747.5247.4643.4938.4
1130.5569.730.59207.84207.84200.82200.8769.6826.1
1272.1675.771.6175.7375.7376.5276.4875.7926.1
13152.30152.5153.5643.4343.43151.93151.23151.9738.4
14118.48118.3118.99--118.11118.07118.31-
15134.06131.3131.69--131.55134.21134.14-
16139.63142.9143.06--143.93140.53139.88-
17134.06131.3131.69--131.55134.21134.14-
18118.48118.3118.99--118.11118.07118.31-
1934.7571.372.18--71.4634.7434.71-
2040.9647.547.63--47.6040.8540.91-
MeO60.2160.260.3560.3960.3960.2360.1960.1960.4
Table 12. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Spiroisoxazolines.
Position424344454649505152
172.475.4175.5074.6074.7373.5573.874.6773.55
2119.6114.24120.80121.66121.80120.81121.4121.85120.88
3145.9149.29149.31147.92148.06147.15147.7148.06147.13
4111.9122.75114.15115.16115.20113.09113.1115.20113.08
5130.1132.30131.32132.15132.36131.25130.6132.30131.20
689.092.3992.6391.7291.8790.3291.991.8790.50
738.540.2640.2140.2740.3042.5338.740.3039.70
8153.3155.34155.29155.10155.17154.47153.9155.18154.37
9157.4161.44161.81160.05160.52158.98160.0160.46159.11
1′72.475.5175.5074.6774.7373.5573.874.6773.55
2′119.6114.24120.80121.66121.80120.81121.3121.8520.84
3′145.9149.29149.31147.92148.06147.15147.7148.06147.11
4′111.9122.75114.15115.16115.20113.09113.1115.20113.08
5′130.1132.30132.25132.31132.36131.25130.6132.30131.20
6′88.992.4592.3691.7891.9390.3291.891.1390.24
7′38.540.2640.0440.2740.3042.5338.740.1639.45
8′153.4155.41154.93155.23155.25154.47153.9154.77154.05
9′157.4161.57161.81160.44160.52158.98160.0160.56158.86
1044.239.0749.1737.1343.9539.0436.247.4948.52
1167.2 (65.7)c33.92206.1830.3769.4771.0468.0201.34204.43
1230.633.5137.5771.5176.1371.0445.076.3238.59
1324.0135.8724.11152.27152.2939.0233.6151.2233.82
1435.0 (32.5)c150.6839.61118.35118.42--118.06-
15-111.32-130.90131.09--131.10-
16-126.67-143.35143.52--144.23-
17-149.52-130.90131.09--131.10-
18-126.09-118.35118.42--118.06-
19-23.09-70.7069.47--70.70-
20-30.10-47.9948.15--48. 01-
21-40.03-------
MeO58.460.4460.3859.7559.8659,6360.059.8659.63
Table 12. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Spiroisoxazolines.
Position535455565758596061
174.175.375.275.074.7374.574.074.568.5
2113.5113.9113.957.457.1157.255.057.254.6
3147.6148.7148.7183.7183.51184.1184.1184.2183.0
4121.2122.0122.0122.5122.45122.7123.0122.7123.2
5131.7132.4132.4149.5149.09149.3146.2149.4146.3
690.791.591.591.491.6791.590.591.490.5
740.040.340.238.638.2438.241.438.241.4
8155.0155.4155.3154.9154.53154.8155.5154.8155.5
9159.3159.9159.9159.7159.76160.1160.1160.1159.7
1′74.175.175.075.074.7874.574.074.568.5
2′113.557.457.557.457.0757.255.057.254.6
3′147.6183.7183.7183.7183.51184.1184.1184.2183.0
4′121.2122.5122.5122.5122.36122.7123.0122.7123.2
5′131.7149.5149.5149.5149.17149.3146.2149.4146.3
6′90.791.591.591.491.4291.590.591.490.5
7′40.038.638.638.638.1038.241.438.241.4
8′155.0154.9154.9154.9154.27154.8155.5154.8155.5
9′159.3159.7159.7159.7159.64160.1160.1160.1159.7
1045.739.739.539.749.1745.945.945.945.9
1167.4 and 68.929.727.529.7204.7068.868.870.370.3
1232.224.727.524.739.6334.634.632.432.4
1325.529.739.529.734.7837.037.026.026.0
1436.639.7-39.7---37.037.0
1534.4--------
1639.4--------
MeO60.160.260.2------
Table 12. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Spiroisoxazolines.
Position626364656667686970
156.975.373.5573.5673.5775.4573.4475.4073.6
253.0113.8120.80120.79120.86122.68120.64122.72120.8
3186.0149.0147.13147.12147.16149.23147.07149.23147.3
4122.8122.0113.04113.04113.11114.12113.00114.10113.1
5143.7132.4131.19131.21131.23132.21131.22132.14131.2
684.091.590.1690.2490.5292.3990.1292.5590.2
743.640.239.5039.5039.3340.1939.5040.0639.3
8154.9155.3154.34154.34154.08155.32154.44155.11154.3
9158.3159.3158.37158.87159.13161.33158.82161.61158.9
1′56.958.1-------
2′53.054.2-------
3′186.0186.0-------
4′122.8124.1-------
5′143.7144.1-------
6′84.085.3-------
7′43.644.5-------
8′154.9155.6-------
9′158.3159.9-------
1038.639.833.8349.8948.5839.4938.5337.8636.2
1126.429.738.29205.66205.75123.4728.2330.7629.4
1226.424.7205.6638.2939.75122.3323.2872.3071.2
1338.629.749.8933.8335.21130.8127.99153.61150.8
14-39.7156.98156.98157.03151.4540.65118.94117.0
15-----118.11157.20131.66133.0
16-------142.82140.6
17-------131.66133.0
18-------118.94117.0
19-------71.6433.7
20-------47.6244.7
21-------173.29-
22-------47.62-
23-------22.68-
MeO-C3-60.259.6059.6059.7960.4259.5660.4259.6
MeO-C14--51.5451.5451.28----
Table 12. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Spiroisoxazolines.
Position71747576798081
175.2173.475.573.5776.476.375.1
2122.15120.8114.1120.87115.1114.9113.8
3148.78147.0149.3147.18150.2150.1149.0
4113.90113.3122.8113.08123.7123.5122.3
5132.27131.2132.3131.21133.2133.0132.3
691.8490.192.390.3393.493.292.6
740.0839.740.239.2641.040.140.0
8155.14154.8155.3154.37156.0159.5153.3
9160.42158.9161.6159.10162.8162.5161.0
1047.7139.439.937.6644.740.563.0
1171.4324.529.824.1278.4-14.4
12138.534.525.6130.7925.7--
13111.38174.761.9133.8440.2--
14130.90-190.6116.21157.5--
15150.72-171.4----
16111.38------
17130.90------
MeO-C360.2259.660.459.6361.359.260.8
Table
Table 13. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Verongiabenzenoids.
Table 13. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Verongiabenzenoids.
Position8283
1154.87152.19
2111.18117.30
3134.63133.35
4129.20135.92
5130.33133.35
6117.68117.30
729.0726.88
868.5165.07
OMe59.8860.31
(Me)3N+53.7752.23
Table
Table 14. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Verongiaquinol.
Table 14. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Verongiaquinol.
Position909798
1172.6183.0183.0
2119.9122.7123.7
3153.2151.7146.6
470.875.574.2
5148.878.478.9
6127.656.157.1
1′-116.9116.9
2′-28.428.4
CH245.1--
CONH2169.4--
Table
Table 15. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Dibromocyclohexadiene.
Table 15. Compilation of the 13C NMR data of the halogenated substances from the genus Aplysina. Dibromocyclohexadiene.
Position101
186.3
2109.1
3149.7
4113.6
5140.4
676.5
742.1
8172.8
960.2
1060.3

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MDPI and ACS Style

Lira, N.S.; Montes, R.C.; Tavares, J.F.; Silva, M.S.d.; Cunha, E.V.L.d.; Athayde-Filho, P.F.d.; Rodrigues, L.C.; Dias, C.d.S.; Barbosa-Filho, J.M. Brominated Compounds from Marine Sponges of the Genus Aplysina and a Compilation of Their 13C NMR Spectral Data. Mar. Drugs 2011, 9, 2316-2368. https://doi.org/10.3390/md9112316

AMA Style

Lira NS, Montes RC, Tavares JF, Silva MSd, Cunha EVLd, Athayde-Filho PFd, Rodrigues LC, Dias CdS, Barbosa-Filho JM. Brominated Compounds from Marine Sponges of the Genus Aplysina and a Compilation of Their 13C NMR Spectral Data. Marine Drugs. 2011; 9(11):2316-2368. https://doi.org/10.3390/md9112316

Chicago/Turabian Style

Lira, Narlize Silva, Ricardo Carneiro Montes, Josean Fechine Tavares, Marcelo Sobral da Silva, Emidio V. L. da Cunha, Petronio Filgueiras de Athayde-Filho, Luis Cezar Rodrigues, Celidarque da Silva Dias, and Jose Maria Barbosa-Filho. 2011. "Brominated Compounds from Marine Sponges of the Genus Aplysina and a Compilation of Their 13C NMR Spectral Data" Marine Drugs 9, no. 11: 2316-2368. https://doi.org/10.3390/md9112316

APA Style

Lira, N. S., Montes, R. C., Tavares, J. F., Silva, M. S. d., Cunha, E. V. L. d., Athayde-Filho, P. F. d., Rodrigues, L. C., Dias, C. d. S., & Barbosa-Filho, J. M. (2011). Brominated Compounds from Marine Sponges of the Genus Aplysina and a Compilation of Their 13C NMR Spectral Data. Marine Drugs, 9(11), 2316-2368. https://doi.org/10.3390/md9112316

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