115 Marine Natural Products Chemistry as an Evolutionary Narrative Guido Cimino* and Michael T. Ghiselin CONTENTS I. Introduction 115 II. The Evolution of Biosynthetic Capacity 117 III. Evolutionary Patterns in Different Classes of Organisms 119 IV. Taxonomic Survey 120 A. Bacteria 120 1. Cyanobacteria 120 B. Algae 120 1. Phaeophyta 122 2. Rhodophyta 122 3. Chlorophyta 125 C. Metazoa 125 1. Porifera 125 2. Cnidaria 129 3. Sessile Filter Feeders with Symbionts: Ectoprocta and Urochordata 131 a. Tentaculata: Phoronida and Brachiopoda 131 b. Tentaculata: Ectoprocta = Bryozoa s.s 131 c. Urochordata 132 4. Sessile Filter or Deposit Feeders Evidently without Symbionts 133 a. Annelida: Polychaeta 133 b. Hemichordata: Enteropneusta and Pterobranchia 135 5. Slow-Moving Grazers and Predators 136 a. Echinodermata 136 b. Platyhelminthes and Nemertea 137 c. Mollusca: Gastropoda 138 V. General Discussion 142 Acknowledgments 143 References 144 I. INTRODUCTION Chemistry is generally looked upon as one of the “nomothetic” sciences, i.e., one that seeks to establish the laws of nature and does not concern itself with particular objects or events. Natural * Corresponding author. 3 9064_ch03/fm Page 115 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC 116 Marine Chemical Ecology products chemistry is an exception, being very much concerned with what are called “individuals” in a broad metaphysical sense. 1 Like geology, paleontology, and systematic zoology, it is very much a natural history discipline. The various natural kinds of secondary metabolites are classes of molecules, and, being classes, they do not evolve any more than does the calcium carbonate that forms the shells of molluscs. What do evolve are individual populations and lineages, which change with respect to the properties of the organisms and their parts, including the enzymes that produce secondary metabolites. Metabolism has a history and we ought to be able to reconstruct that history just like the chemical and physical aspects of defense. There seems to have been an arms race between shelled molluscs and the crabs that have preyed upon them. 2 A chemical arms race involving molluscs in which the shell has become reduced is a straightforward extrapolation. It is no longer fashionable to dismiss secondary metabolites as mere waste products or as substances that no longer play an important role in the lives of organisms. They are distributed in the body very much like other features that have obvious value in the struggle for existence. 3 Even today, however, much of the discussion of the supposed function of natural products continues to treat natural selection as little more than background material. Indeed, historical situations are often invoked to explain away anomalies where efforts to find adaptation fail. Adaptation can be treated as if it were nothing more than a condition or state. At least implicitly, however, the product is defined in terms of the process. In other words, when we claim that something is an adaptation, we presuppose a historical narrative, even if the narrative is concerned only with the very recent past. If we really want to understand the adaptive significance of secondary metabolites, we need to ask some truly historical questions. These authors’ contributions in this area have mainly dealt with the evolution of chemical defense in opisthobranch gastropods. 4,5 Faulkner and Ghiselin 6 addressed the question of whether the reduction of the shell in these animals preceded the evolution of chemical defense (a post- adaptive scenario) or whether the loss of the shell was made possible by the presence of chemical defense (a pre-adaptive scenario). The latter hypothesis was preferred on the grounds that in groups in which the shell is relatively well developed, chemical defense is already present. The reasoning is basically a matter of plotting features on the branches of a phylogenetic tree and inferring the sequence of events. But the biological plausibility of the sequence in question may provide an additional line of evidence. This is a traditional mode of reasoning that goes back to Darwin and his follower Anton Dohrn, who founded the Zoological Station at Naples. 7,8 Evolution proceeds by steps; in each step the functioning of the organism as a whole is conserved, but particular functions often succeed one another over time. Various patterns in the evolution of chemical defense have been documented, including detox- ification, modification and sequestration of metabolites, and their positioning in places where they will more effectively repel predators. Of particular interest is the evolution of de novo synthesis. The work of these authors has suggested how this might happen. It also suggests that asking questions about the evolution of biosynthetic capacity might provide a unifying theme for the study of natural products chemistry. This chapter first discusses how chemical defense might be acquired. The authors then suggest reasons why it should evolve differently in various kinds of organisms such as autotrophs and heterotrophs. The chapter then gives some examples, presented in an order that is not, strictly speaking phylogenetic, although the taxonomic groups discussed are generally thought to be natural ones in the sense that they represent genealogical wholes (clades). The opisthobranchs are discussed in more than one place because they derive metabolites from various sources, including de novo synthesis. The acquisition and use of some metabolites rather than others provides evidence that they are, as suspected, defensive chemicals. However, they may be defensive in a broad sense that includes dealing with fouling organisms, spatial competitors, and various other things. 9064_ch03/fm Page 116 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC Marine Natural Products Chemistry as an Evolutionary Narrative 117 II. THE EVOLUTION OF BIOSYNTHETIC CAPACITY It is well understood that the synthesis and modification of metabolites is under enzymatic control. The enzymes may function as catalysts, and the reactions themselves are not restricted only to living systems. So the evolution of biosynthetic capacity is largely the result of changes in enzymes by mutation, gene duplication, and other familiar processes. The organisms synthesize and modify secondary metabolites in a stepwise fashion, much as organic chemists do, and in neither case are the laws of nature violated. The term “secondary metabolite” is generally understood to mean that the chemicals in question are not directly involved in the basic maintenance of the organism. Secondary metabolites are produced from a remarkably limited range of starting materials known as primary metabolites. There are three major classes of secondary metabolites of interest here (Figure 3.1). Acetogenins are produced by head-to-tail condensation of acetic acid into linear units starting with acetyl-CoA. Terpenes are made from acetate units that are turned into isoprene units and then put together into larger units by head-to-tail condensation via isopentenyl diphosphate, often followed by cyclization. Finally, alkaloids are usually formed by the Mannich reaction in which amino acids are transformed into amines and aldehydes. There are, of course, less common metabolites, sometimes very inter- esting ones. These include the polypropionates, discussed later in this chapter. As shown in Figure 3.1, they form similar to acetogenins, but the starting compound is propionyl CoA. Aceto- genins and polypropionates are often referred to in the literature as polyketides. One should bear in mind that much of the diversity of metabolites can be explained as a result of stepwise synthesis of larger and larger units, with some divergent variants in skeletal structure and a lot of rearrange- ments and other modifications of the basic structures. Such patterns of synthesis can be explained historically, and stepwise modification of biosynthetic pathways through time is a basic phylogenetic theme. The fact that the same compound may be synthesized by different pathways is not an impediment to such historical analysis, but rather an opportunity. Different pathways often reflect separate historical origins. Before discussing how organisms might evolve such pathways, it is convenient to consider how they might acquire pathways from other organisms. One such possibility is through symbiosis, especially mutualism. Such mutualism is well documented in the phylum Porifera, or sponges, which often contain bacteria within their tissues that produce some of the metabolites that defend the sponge and presumably the bacteria as well. The sponges did not have to evolve the chemicals that defend them. Another possibility is lateral gene transfer. The well-known spread of antibiotic resistance between lineages of bacteria makes such a transfer seem highly plausible. Lateral gene transfer may be quite common among marine microorganisms. 9 It can enable them to acquire the capacity for biosynthesis without having to evolve it through the modification of pre-existing metabolic apparatus. Such capacity means that the organisms are not constrained by the necessity of obtaining the metabolites from symbionts or food. But whether such a transfer is not just possible, but has in fact occurred, has to be established on the basis of empirical evidence. For multicellular animals it is mere conjecture. We have suggested elsewhere that there are two modes by which the capacity for biosynthesis of secondary metabolites might evolve. 5 The first of these is the straightforward and well-documented anasynthetic mode in which more and more steps are added and, perhaps, a molecule of increasing size is produced. Such evolution has been well documented in terrestrial plants, and some marine examples are discussed below. In some cases it has been shown that the end product of the most derived evolutionary stage is accumulated in the tissues, but that the intermediates are present in lesser concentrations. These intermediates, however, may be the metabolites that are concentrated in the tissues of related forms that represent ancestral conditions in a historical sequence. This case presents a chemical analogue of the traditional notion that ontogeny recapitulates phylogeny. 10 Such recapitulation occurs only under restricted conditions, namely, where there has been terminal addition 9064_ch03/fm Page 117 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC 118 Marine Chemical Ecology of new stages. There is nothing to prevent the secondary loss of developmental or biosynthetic stages, and it is possible that earlier steps in a pathway might be affected. Another possibility is called the retrosynthetic mode. We recognized this possibility because opisthobranchs have evolved the capacity for de novo synthesis of metabolites similar to those that they originally derived from food. How could they evolve an entire pathway that supposedly had not been part of their evolutionary heritage, a process that usually takes a long time and a lot of unusual events? One possibility was lateral gene transfer. However, the metabolites in question sometimes did not have the same chirality as those in the food organisms, suggesting that different FIGURE 3.1 Main classes of secondary metabolites. Fatty acids and acetogenins are derived from acetyl Coenzyme A, which forms the isopentyl diphosphate that forms terpenes. The (unusual) polypropionates derive from propionyl CoA. Alkaloids are typically modified amino acids. H 3 C CH 2 CH 2 CH 2 CH 2 C OH O H 3 C C CH 2 C CH 2 C OH OOO O C H 3 C CoA OPP H CH 2 C CH C CH C OH OOO O C CH 2 CoA CH 3 CH 3 CH 3 CH 3 n N H NH 2 n fatty acid N H N acetogenin (a) acetyl CoA H 3 C C O C O isopentenyl diphosphate n (1-7) terpene (b) n OH polypropionate (c) propionyl CoA tryptamine + pyruvic acid 1-methyl-β-carboline alkaloid (d) 9064_ch03/fm Page 118 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC Marine Natural Products Chemistry as an Evolutionary Narrative 119 enzymes of different historical origins are involved. The chirality is just one example of the fact that when nudibranchs have evolved de novo synthesis, the metabolites that they produce, although similar, are almost never identical to the originals. So, elaborating on some earlier ideas, 11,12 we proposed that the predators first evolved the ability to modify the last stages of a biosynthetic pathway while still relying upon intermediates that are available in food. Given that the intermediates are present in the food, any mutation that increases their concentration would be selectively advantageous. Steps in the synthesis could be added backward until replacing a point in which a precursor was available that the predator could synthesize on its own. This would clearly not be a situation in which ontogeny recapitulates phylogeny. III. EVOLUTIONARY PATTERNS IN DIFFERENT CLASSES OF ORGANISMS Classes of organisms refers here to abstract kinds, as opposed to taxonomic groups, which are concrete historical units. Classes here means groups of organisms that share such properties as the manner in which food is obtained, whether they are sessile or motile, large or small, etc. Large, sessile autotrophs have evolved separately and independently upon numerous occasions. So have filter-feeders, grazers, and predators. These groups of unrelated organisms have many of the same ecological requirements and functional constraints. They often display some evolutionary conver- gences that help us infer what the important selection pressures have been. Microorganisms include prokaryotes (bacteria such as Cyanobacteria) and unicellular eukary- otes (Protozoa and algae of various taxa). Because of their small size and considerable biosynthetic versatility, they are predisposed to assume the position of mutualistic symbionts within the bodies of other organisms. Lateral gene transfer is, of course, particularly well documented in bacteria. Unicellular organisms that remain together as a group and form clones can defend the group as a whole in the same way that an entire multicellular organism does. Part of the unit can be sacrificed, leaving the rest still able to survive and reproduce. Sessile autotrophs in marine environments are almost all algae. Many algae remain unicellular, but there are several lineages which are multicellular organisms crudely convergent with terrestrial plants. Because the source of nutriment is photosynthesis, multicellular plants have no dietary source of secondary metabolites, and, furthermore, the opportunities for evolving symbiotic rela- tionships that might provide defense are quite limited. So, we would expect the anasynthetic mode to be virtually the only way of acquiring chemical defense in such organisms. On the other hand, the sessile life style, where organisms cannot move away from either grazers or spatial competitors, makes chemical defense a particularly important mechanism. There are, to be sure, examples of terrestrial plants with defensive symbiotic relationships, for example, with ants, and there may be some marine examples as well. Sessile animals (and ones that are virtually so) have much the same problems in defending themselves and warding off predators as terrestrial plants. In fact, many of these animals supplement their food supply by means of symbiotic unicellular organisms, as do a few animals that move from place to place, but slowly. Most sessile marine animals feed upon material that is either suspended in the water or deposited on the substrate. This material sometimes contains metabolites that might be put to use defensively. However, the food is usually heterogeneous and relatively unpredictable as to content; therefore, it does not supply a reliable source of metabolites. It is generally not used defensively, and such use is facultative. Some bivalves, however, do concentrate saxitoxin, derived from dinoflagellates, in tissues that are exposed to predators. 13 A large number of sessile filter feeders do have defensive metabolites that are not derived from food. Some of these metabolites are synthesized by the animals themselves, and some are synthe- sized by symbionts. In the latter case, there must be a reliable way of providing a supply of symbionts for the next generation. This is especially important because sessile and sedentary marine 9064_ch03/fm Page 119 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC 120 Marine Chemical Ecology animals generally disperse as larvae or as in even earlier developmental stages. Special adaptations that transmit the guest symbionts from host to host across generations are presumptive evidence that the host species actually receives a benefit, i.e., that the host is either a mutualist or a parasite. Of course, unwelcome guests often do succeed in getting transmitted from parent to offspring, but this occurs in spite of the noncooperation of the host. In that case the parasite is the exploiting organism, and is not necessarily contained within the other organism, so an ectoparasite could actually surround its host. Slow-moving grazers are also in a poor position to flee from predators and require some sort of suitable protection, either mechanical, chemical, or both. Spatial competitors and fouling organ- isms are less of a problem. Depending on what they eat, it may or may not be easy for them to obtain defensive metabolites from food. If they do obtain such metabolites from food, one would expect them to be specialists that feed upon organisms of those taxa that contain a copious and reliable supply of such metabolites. Obtaining defensive metabolites from symbionts is a distinct possibility, but there is little evidence of that in these organisms. The difficulty of overcoming the food organism’s chemical (and mechanical) defenses combined with relying upon that same organ- ism as a source of protective metabolites tends to produce specialization, yet it constrains the animal to a narrower range of food items. Hence one might predict shifts of host and the evolution of a capacity for de novo synthesis. IV. TAXONOMIC SURVEY A. B ACTERIA The bacteria of interest to us here are restricted to one major clade of Eubacteria: the Actinobacteria and the closely related Cyanobacteria. They are particularly significant as sources of metabolites that are used by other organisms, either because the other organisms are their symbionts or feed upon them. A few fungi are also significant for the same reason. The possible origin of their use of such compounds has been subject to some speculation. A reasonable possibility is that the metabolites were used in competing with other prokaryotes, perhaps in or on the surface of sediments. The bacterial metabolites of interest here are macrolides, polyketides, cyclic lactones, cyclic peptides, and alkaloids (Figure 3.2). Macrolides of sponges are produced by symbiotic bacteria in their tissues. Polyketides of urochordates are also produced by symbiotic bacteria, and these are concentrated by the opisthobranch gastropods that feed upon them. Figure 3.2 shows typical metabolites from bacteria and fungi. 1. Cyanobacteria Some characteristic metabolites of Cyanobacteria are macrolides and chlorinated amides (Figure 3.3). Cyanobacteria were formerly called blue-green algae, and, as the name suggests, some of them are convergent with the prokaryotic algae in general structure and also in sometimes containing secondary metabolites. In the opisthobranch order Anaspidea, there are isolated cases of shifts from feeding on true algae to including Cyanobacteria in the diet. The availability of metabolites that could be used defensively in food organisms with suitable physical properties can be viewed as allowing an opportunistic shift in niche. However, the anaspideans are remarkably adept at coping with a broad range of metabolites, and an alternative scenario in which Cyano- bacteria were present in the diet from a much earlier period cannot presently be excluded. B. A LGAE This section discusses the three groups of algae within which multicellular, mainly sessile lineages have evolved. All three groups have members rich in secondary metabolites that are pressed into service defensively by opisthobranchs that feed upon them. Presumably, they are also used 9064_ch03/fm Page 120 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC Marine Natural Products Chemistry as an Evolutionary Narrative 121 FIGURE 3.2 Selected metabolites after marine bacteria and fungi. 3.2.1 Saxitoxin. 173 3.2.2 Swinholide from Theonella swinhoei . 174 3.2.3 Lagunapyrone A from an actinomycete. 175 3.2.4 (-)Macrolactin A from an uniden- tified deep-sea bacterium. 176 3.2.5 Loloatin B from Bacillus sp. isolated from an unidentified tube worm. 177 3.2.6 Penochalasin A, from Penicillum sp., symbiotic with the green alga Enteromorpha intestinalis . 178 3.2.7 6- Bromindole-3-carbaldehyde from the ascidian Stomozoa murrayi and an associated Acinetobacter sp. 179 3.2.8 Gymnastatin A from a strain of Gymnasella dankaliensis isolated from the sponge Halichondria japonica . 180 + OMe HO HO O OMe OH O OHOO MeO OHOH O OMe HO O OOHO O H 3 C O OH HO OH OO HO HO OH HN NH HN O O N H O H 2 NOC N H Ph NH HOOC O Ph NO O H N O OH O N H O H N H N O CH 2 NH 2 N H HN O H O NH O N H Br CHO Cl O Cl O N H CC 6 H 13 O N N H H 2 N OCONH 2 N H H N NH 2 3.2.2 OH OH 3.2.3 H 3.2.4 3.2.5 3.2.6 3.2.7 3.2.8 3.2.1 + 9064_ch03/fm Page 121 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC 122 Marine Chemical Ecology defensively by plants, though, again, the wider range of effects upon other organisms under that rubric is included. The differences between these three groups in the kinds of metabolites that they elaborate suggest separate historical origins. The possibility that these metabolites could be traced back to an earlier common ancestry cannot be ruled out, but there seems to be no evidence for that theory. What has been documented is the elaboration and diversification of metabolites within each of these major algal groups. 1. Phaeophyta The first algal lineage considered here is the brown algae, or Phaeophyta, which include the familiar, macroscopic kelps. This chapter does not go into the fascinating and highly controversial issue of whether polyphenolics in brown algae are used defensively (see Chapter 6 in this volume). These compounds are not expropriated by algivorous animals, and indeed, there would seem to be no defensive use of these compounds by any animals. Terpenoids are another matter altogether. Dolabellanes (Figure 3.4.7), for example, are highly toxic compounds. They are named after the genus Dolabella , which are opisthobranchs of the order Anaspidea (see below). Amico 14 studied the secondary metabolites in brown algae of the genus Cystoseira (family Cystoseiraceae, order Fucales) from a phylogenetic point of view. He was able to arrange metab- olites in series, such that the more evolutionarily derived algae have metabolites that require more steps in their biosynthesis (Figure 3.4). Linear diterpenoids in his scheme are succeeded by what he calls a pool of open-chain meroditerpenoids, and these in turn are elaborated into several groups of derived and divergent ring systems. His arrangement agreed well with morphological classifi- cations and made sense in terms of the biogeography of the group. Because the genus originated in the late Cretaceous period (ca. 80 MYBP), it seems clear that the elaboration and diversification of the metabolites occurred during the Cenozoic Period. 2. Rhodophyta Important metabolites of red algae are shown in Figure 3.5. Red algae have traditionally been divided into Bangiaceae and Floridiophycidae. The former are morphologically simpler, and efforts to find defensive metabolites in them have failed. On the other hand, C-15 halogenated acetogenins and halogenated monoterpenoids are widespread among the latter. Within the Floridiophycidae, halogenated monoterpenes predominate in the Gigartinales, whereas the Ceramiales emphasize brominated sesquiterpenes. Other significant metabolites of red algae include sesquiterpenoids, diterpenoids, polyethers, and dipeptides. Opisthobranchs of the order Anaspidea (sea hares) feed upon a diversity of algae. That they sometimes obtain metabolites from blue-green algae (Cyanobacteria) and brown algae (Phaeophyta) has already been mentioned. They also feed upon green algae (Chlorophyta, see below), but these FIGURE 3.3 Selected metabolites from cyanobacteria. 3.3.1 Laingolide from Lyngbya bouillonii . 181 3.3.2 Malyngamide from Lyngbya majuscula . 182 C 7 H 15 Me N Cl O OH OOMe 3.3.2 N O Me O O 3.3.1 9064_ch03/fm Page 122 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC Marine Natural Products Chemistry as an Evolutionary Narrative 123 are not known to provide them with an important source of metabolites. A remarkably wide range of chlorinated terpenoids has been recovered from red algae, especially from the genus Laurencia and from sea hares of the genus Aplysia that feed upon them. The ability to feed upon algae that are rich in halogenated terpenoids seems to have been a major innovation within the Anaspidea, but the group in general is adept at feeding upon plants with a broad range of algal metabolites. To what extent the anaspideans are expropriating the metabolites and using them defensively, and to what extent they are merely obtaining them from food and disposing of them, has been a topic of controversy. It has been pointed out that the metabolites are mostly concentrated in the FIGURE 3.4 Metabolites of brown algae. 3.4.1–3.4.6 Selected metabolites from the Cystoseira showing simple and derived conditions. 183 3.4.7 Dictyotatriol A from Dictyota dichotoma . 184 OH H HO H HO 3.4.7 OH OMe O O H HO 3.4.6 O OMe OH O 3.4.5 O OOH OMe OH 3.4.4 OMe OH O O O OH 3.4.3 O O 3.4.2 OH 3.4.1 9064_ch03/fm Page 123 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC 124 Marine Chemical Ecology digestive gland, which is not where they would most effectively deal with predators. 15 However, evolution from a relatively ineffective mechanism of defense to a more effective one is what is expected and has precedents in other groups of opisthobranchs. Some oversimplifications about selective mechanisms may be implicit in such discussions. It is generally assumed that a defensive adaptation cannot evolve if the organism that possesses it is killed and therefore fails to reproduce more than conspecifics without it. This stricture would apply to the anaspideans in question were it a scenario with metabolites becoming present in the digestive gland because of their defensive role. It does not apply, however, to a scenario in which the metabolites were initially present in the food and, therefore, in the digestive gland. An animal containing such metabolites in its digestive gland would not be protected from predators that devoured it. But if the predators were sickened or killed, they would tend to leave the survivors alone. Selection could then favor putting the metabolites in a more effective position. Kin selection might also operate in spite of some theoretical considerations first put forth by Faulkner and Ghiselin, 6 and subsequently by other authors. 16,17 The problem with kin selection in opisthobranchs is that most of them have larval dispersal, and, therefore, the juveniles and adults do not live with close relatives. Under such circumstances, kin selection does not seem to be a good explanation for the aposematic coloration that is so common in the group. One important point, however, has been overlooked. Opisthobranchs are internally fertilizing hermaphrodites that store sperm, and they often occur in aggregations of conspecifics. FIGURE 3.5 Selected metabolites from red algae. 3.5.1 Pannosallene from Laurencia pannosa . 185 3.5.2 Pantafuranoid A from Pantoneura plocamioidea . 186 3.5.3 Rigidol from Laurencia rigida . 187 3.5.4 10-Epide- hydroxythyrsiferol from Laurencia viridis . 188 3.5.5 Almazole D from Haraldiophyllum sp. 189 N H O N O HO Ph NMe 2 3.5.5 O O O O OH OH H HH Br 3.5.4 HO Br OH 3.5.3 O Br H HO Br 3.5.2 O O Br Br 3.5.1 9064_ch03/fm Page 124 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC [...]... from Bulla gouldiana. 230 3. 13. 5 10-Isocyano-4-cadinene from Phyllidia spp. 231 3. 13. 6 7α-Hydroxyspongian-16-one from Chromodoris obsoleta. 232 3. 13. 7 Dolabriferol from Dolabrifera dolabrifera. 233 3. 13. 8 Noloamine from Smaragdinella calyculata. 234 3. 13. 9 Pinnatoxin D, from Pinna muricata. 235 3. 13. 10 Elysione from Elysia chlorotica. 236 3. 13. 11 Cyercene A from Cyerce crystallina. 237 3. 13. 12 Nordolastin G from... OH O O OH 3. 13. 5 3. 13. 6 3. 13. 7 HN + O H O O HO N O COO- O O NH2 OH 3. 13. 8 3. 13. 9 Me N O N OMe O O O MeO O O O O N Me O N MeO O O Me N Me O N OH O 3. 13. 10 O O 3. 13. 11 O 3. 13. 12 FIGURE 3. 13 Selected metabolites from molluscs 3. 13. 1 Dentaculatin A, from Siphonaria denticulata.227 3. 13. 2 Onchidal from Onchidella binneyi.228 3. 13. 3 Testudinariol A from Pleurobranchus testudinarius.229 3. 13. 4 (-) Isopulo’upone... Press LLC 9064_ch 03/ fm Page 134 Tuesday, April 24, 2001 5:16 AM 134 Marine Chemical Ecology O HO NHCOOMe Ph S MeSSS O N O O H N MeS O HO Ph O O O HO O H N N H 3. 10.2 OMe MeS N HN OH O 3. 10.1 N N Ph OH O S O 3. 10.4 N H O NH N HN O Br O O N NH O O N N O CH3 H N CH3 H NH N 3. 10.5 3. 10 .3 O N H N H OH NH2 3. 10.6 N H H O O H3CO O 3. 10.7 HO 3. 10.8 N N N HO S OH H3CO 3. 10.9 N OH O 3. 10.10 FIGURE 3. 10 Selected... CRC Press LLC 9064_ch 03/ fm Page 144 Tuesday, April 24, 2001 5:16 AM 144 Marine Chemical Ecology HO HO AcO O AcO O OH O OAc O O 3. 14.1 3. 14.2 3. 14 .3 AcO O O OH O H OAc 3. 14.4 OAc 3. 14.5 O H H O O H H H H O H H H 3. 14.6 3. 14.7 3. 14.8 FIGURE 3. 14 Selected metabolites biotransformed or biosynthesized by opisthobranch gastropods 3. 14.1 Deoxoscalarin from Hypselodoris orsini. 239 3. 14.2 6-Ketodeoxoscalarin from... Onchidium 138 , 139 and Peronia.140 In the genus Onchidella, the repugnatorial secretion consists largely of the enol acetate sesquiterpenoid onchidial (Figure 3. 13. 2).141,142 © 2001 by CRC Press LLC 9064_ch 03/ fm Page 139 Tuesday, April 24, 2001 5:16 AM Marine Natural Products Chemistry as an Evolutionary Narrative 139 OH H O CHO O O OAc OH 3. 13. 1 3. 13. 2 O H H O O H H N H HO OH H 3. 13. 3 H 3. 13. 4 H NC O... bacterial symbionts. 93 © 2001 by CRC Press LLC 9064_ch 03/ fm Page 132 Tuesday, April 24, 2001 5:16 AM 132 Marine Chemical Ecology O HO O MeOOC HN O O O N H O N Cl OH HN O Br OH 3. 9.1 O OH MeOOC O HO OH n 3. 9.2 n = 11 - 12 3. 9 .3 FIGURE 3. 9 Selected metabolites from bryozoans and a brachiopod 3. 9.1 Securine A from Securiflustra securirons.209 3. 9.2 Bryostatin 18 from Bugula neritina.210 3. 9 .3 Glycerol ethers... been rejected.62, 63 Negative evidence about feeding deterrence by fish turned out to be the result of the fish not responding immediately but vomiting after a delay.64 The delay, coupled with © 2001 by CRC Press LLC 9064_ch 03/ fm Page 130 Tuesday, April 24, 2001 5:16 AM 130 Marine Chemical Ecology O O O O O O C5H11 O 3. 8.1 3. 8.2 O O HO N HO SMe HO 3. 8 .3 H SMe 3. 8.4 H O O 3. 8.5 FIGURE 3. 8 Selected metabolites... Figure 3. 12.) OH NaO3SO HO HO HO OH Me O HO HO HO Me O HO O O HO HO O O O O O HO OSO3Na Me 3. 12.1 O OH OH HO HO OH 3. 12.2 HO NH OH NH N H NH2HCl 3. 12 .3 FIGURE 3. 12 Selected metabolites from echinoderms 3. 12.1 Comasteride A from Comasterias lurida.224 3. 12.2 A polyhydroxylated sterol from Stylaster caroli.225 3. 12 .3 Fuscusine from Perknaster fuscus.226 © 2001 by CRC Press LLC 9064_ch 03/ fm Page 137 Tuesday,... metabolites .32 That fits the notion of an arms race with a shift from mechanical to chemical defense © 2001 by CRC Press LLC 9064_ch 03/ fm Page 127 Tuesday, April 24, 2001 5:16 AM Marine Natural Products Chemistry as an Evolutionary Narrative 127 OMe OMe Br Br Br Br NC HO OH O O O H N H N N O N O 3. 7.1 3. 7.2 OMe O N H H Cl O N H 3. 7 .3 O 3. 7.4 3. 7.5 O HO H O HO O H O O O 3. 7.6 3. 7.7 CHO AcO CHO COOH OH 10 3. 7.8 3. 7.9... Figure 3. 7 Some of these are biosynthesized by the sponges themselves, but others are biosynthesized by bacterial © 2001 by CRC Press LLC 9064_ch 03/ fm Page 126 Tuesday, April 24, 2001 5:16 AM 126 Marine Chemical Ecology OH OH Ph O O H N N H H N N H O COOH O O N O O 3. 6.2 O HN NH AcO O HO OHC 3. 6.1 AcO O H OAc 3. 6.4 CH2OH OAc Br 3. 6 .3 OH Br OH OH 3. 6.5 FIGURE 3. 6 Selected metabolites from green algae 3. 6.1 . O O N H O H 2 NOC N H Ph NH HOOC O Ph NO O H N O OH O N H O H N H N O CH 2 NH 2 N H HN O H O NH O N H Br CHO Cl O Cl O N H CC 6 H 13 O N N H H 2 N OCONH 2 N H H N NH 2 3. 2.2 OH OH 3. 2 .3 H 3. 2.4 3. 2.5 3. 2.6 3. 2.7 3. 2.8 3. 2.1 + 9064_ch 03/ fm Page 121 Tuesday, April 24, 2001 5:16 AM © 2001 by CRC Press LLC 122 Marine Chemical Ecology defensively. dichotoma . 184 OH H HO H HO 3. 4.7 OH OMe O O H HO 3. 4.6 O OMe OH O 3. 4.5 O OOH OMe OH 3. 4.4 OMe OH O O O OH 3. 4 .3 O O 3. 4.2 OH 3. 4.1 9064_ch 03/ fm Page 1 23 Tuesday, April 24, 2001 5:16 AM ©. cyanobacteria. 3. 3.1 Laingolide from Lyngbya bouillonii . 181 3. 3.2 Malyngamide from Lyngbya majuscula . 182 C 7 H 15 Me N Cl O OH OOMe 3. 3.2 N O Me O O 3. 3.1 9064_ch 03/ fm Page