8.07 Marine Natural Products and Marine Chemical Ecology JUN’ICHI KOBAYASHI and MASAMI ISHIBASHI Hokkaido University, Sapporo, Japan 7[96[0 INTRODUCTION 305 7[96[1 FEEDING ATTRACTANTS AND STIMULANTS 306 7[96[1[0 Fish 306 7[96[1[1 Mollusks 307 7[96[2 PHEROMONES 319 7[96[2[0 Sex Attractants of Al`ae 319 7[96[2[1 Others 315 7[96[3 SYMBIOSIS 315 7[96[3[0 Invertebrates and Microal`ae 315 7[96[3[1 Others 318 7[96[4 BIOFOULING 329 7[96[4[0 Microor`anisms 329 7[96[4[1 Hydrozoa 320 7[96[4[2 Polychaetes 321 7[96[4[3 Mollusks 321 7[96[4[4 Barnacles 324 7[96[4[5 Tunicates 339 7[96[5 BIOLUMINESCENCE 333 7[96[5[0 Sea Fire~y 333 7[96[5[1 Jelly_sh 335 7[96[5[2 Squid 343 7[96[5[3 Microal`ae 346 7[96[6 CHEMICAL DEFENSE INCLUDING ANTIFEEDANT ACTIVITY 348 7[96[6[0 Al`ae 348 7[96[6[1 Mollusks 351 7[96[6[2 Spon`es 354 7[96[6[3 Other Invertebrates 369 7[96[6[4 Fish 362 7[96[7 MARINE TOXINS 365 7[96[7[0 Cone Shells 365 7[96[7[0[0 Conus geographus 365 7[96[7[0[1 Other Conus toxins 367 7[96[7[1 Tetrodotoxin and Saxitoxin 379 7[96[7[1[0 Tetrodotoxin 379 7[96[7[1[1 Saxitoxin 374 7[96[7[1[2 Sodium channels and TTX:STX 375 7[96[7[2 Diarrhetic Shell_sh Poisonin` 378 7[96[7[2[0 Okadaic acid and dinophysistoxin 389 7[96[7[2[1 Pectenotoxin and yessotoxin 386 304 305 Marine Natural Products and Marine Chemical Ecolo`y 7[96[7[3 Ci`uatera 490 7[96[7[3[0 Ci`uatoxin 490 7[96[7[3[1 Maitotoxin 493 7[96[7[3[2 Gambieric acid 497 7[96[7[4 Other Toxins 498 7[96[7[4[0 Palytoxin 498 7[96[7[4[1 Brevetoxin 400 7[96[7[4[2 Suru`atoxin 404 7[96[7[4[3 Polycavernoside 404 7[96[7[4[4 Prymnesin 407 7[96[7[4[5 Pinnatoxin 407 7[96[8 BIOACTIVE MARINE NATURAL PRODUCTS 410 7[96[8[0 Dru` Candidates 410 7[96[8[1 Topics on Tunicates 410 7[96[8[1[0 Vanadium accumulation by tunicates 410 7[96[8[1[1 Eudistomins and related alkaloids 414 7[96[8[1[2 New tunicate metabolites 418 7[96[8[1[3 Pseudodistomins 436 7[96[8[2 Spon`e Metabolites 442 7[96[8[2[0 Manzamines and related alkaloids 442 7[96[8[2[1 Metabolites of the `enus Theonella 456 7[96[8[2[2 Others 472 7[96[8[3 Microbial Metabolites 476 7[96[8[3[0 Bacteria 476 7[96[8[3[1 Fun`i 488 7[96[8[3[2 Blue!`reen al`ae 592 7[96[8[3[3 Dino~a`ellates and other microal`ae 502 7[96[8[3[4 Amphidinolides 508 7[96[09 REFERENCES 523 7[96[0 INTRODUCTION The oceans cover nearly 69) of the whole surface area of the earth and more than 29 phylums and 499 999 species of marine organisms live in them[ In the oceans the circumstances are quite di}erent from those on the land[ The undersea environment is a closed system with high salinity\ high pressure\ and relatively constant temperature[ Animals\ plants\ and microorganisms living in the ocean therefore are expected to produce quite di}erent secondary metabolites from those produced by terrestrial organisms[ Since the 0869s\ a great number of new marine natural products have been isolated from various marine organisms[ Most of these marine natural products possess a variety of unique chemical structures that have never been encountered among natural products of terrestrial origins\ whereas these marine natural products frequently exhibit interesting biological activity which may be of great importance in many _elds of biological sciences[ The aims of research projects concerned with marine natural products may be "i# to _nd novel compounds that are useful as leads for drug development\ "ii# to provide good tools for basic studies of life science\ and "iii# to study the roles and biological functions of secondary metabolites in the life of marine organisms[ The third subject\ which is called {{marine chemical ecology\|| has\ since the mid 0879s\ become a _eld of study[ This chapter describes studies on marine natural products\ particularly those of interest from the viewpoint of marine chemical ecology\ and consists mainly of two parts[ The _rst part deals with marine natural products related to marine chemical ecology[ Classi_cation of the phenomena associated with marine chemical ecology is arbitrary\ and here we describe them in seven sections "Sections 7[96[1Ð7#[ In the latter part of this chapter "Section 7[96[8#\ topics in marine natural products chemistry are described from various viewpoints irrespective of the relationships to eco! logical subjects[ As the dividing line between the sections may sometimes be obscure\ the selection of compounds and topics is arbitrary and not necessarily comprehensive[ A series of excellent reviews on marine natural products chemistry\ published by Faulkner\0Ð01 cover all the literature describing marine natural products\ organized phylogenetically[ A special issue of Chemical Reviews appeared in 0882\02 providing broad aspects of contributions on marine natural products chemistry[ The present authors wrote a review in 088103 covering the nitrogen! containing secondary metabolites isolated from marine organisms\ mainly reported in the late 0879s[ Marine Natural Products and Marine Chemical Ecolo`y 306 Several good books or reviews dealing with general or specialized subjects in marine natural products research have been published\04Ð10 in particular\ those describing the role of marine natural products in chemical ecology[11Ð14 7[96[1 FEEDING ATTRACTANTS AND STIMULANTS Feeding is one of the most fundamental behaviors of all living organisms[ It was suggested by many biological studies that chemical substances or chemical changes in the environment may initiate the feeding behavior of marine organisms and promote the ingestion of foods\ and those chemicals may be designated as {{attractants|| and {{stimulants\|| respectively[ This sections deals with studies of feeding attractants and stimulants of marine animals[ Excellent reviews have been published on this subject by Sakata[15Ð17 This section contains descriptions of feeding attractants of stimulants of particularly _sh and mollusks[15Ð18 7[96[1[0 Fish It is well known that chemical substances participate in feeding behaviors of _sh and this phenomenon is called {{chemoreception[|| Fish possess a sense of smell and taste and their sensitivity is much higher than that of man "Table 0#[17 The gustatory organs "taste buds# of _sh are distributed not only in the mouth but also on the palp\ lip\ and skin[ The senses of taste and smell cannot be clearly categorized for _sh because signal communications by chemical substances are mediated with water[ It has been suggested that the gustatory organs of _sh may play a role in receiving signals of chemical substances over long distances[ Table 0 Comparison of taste sensitivity of man and _sh[17\29 *ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Lowest concentration of taste "mol l−0# *ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Substance Man Fisha Ratio *ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Ra.nose 0:134 659 Sucrose 0:80 0:70 810 899]0 Lactose 0:05 0:1459 059]0 Glucose 0:02 0:19 379 0464]0 Galactose 0:8 0:4019 458]0 Fructose 0:13 0:50 339 1459]0 Arabinose 0:02 0:04 259 0071]0 Saccharin 0:8980 0:0 425 999 058]0 Quinine hydrochloride 0:0 929 817 0:13 465 999 13]0 Sodium chloride 0:099 0:19 379 194]0 Acetic acid 0:0149 0:193 799 053]0 *ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ a Cypriniformes family[ Hashimoto et al[20 studied feeding attractants and stimulants of the eel An`uilla japonica in extracts of mussels Tapes japonicus by watching the behavior of eels using samples mixed with gelatin[ Seven amino acids were isolated in the active fraction\ and among them the e}ective concentrations of glycine "Gly#\ L!alanine "Ala#\ and L!arginine "Arg# were revealed to be 1×09−4 mM\ 0×09−6 mM\ and 4×09−7 mM\ respectively[ Mixtures of these amino acids were more e}ective than each pure amino acid\ suggesting that the synergetic e}ect of amino acids may be important[ Quaternary ammonium salts\ nucleic acid derivatives\ and organic acids proved to be inactive[ Amino acids were generally identi_ed as feeding attractants and stimulants of _sh of other kinds "Table 1#[ They were mostly normal amino acids such as Gly\ Ala\ and Arg\ while unusual amino acids were also reported such as arcamine "0# and strombine "1#[21 In addition to amino acids\ inosine\ inosine!4?!monophosphate "4?!IMP "2##\ adenosine!4?!monophosphate "4?!AMP "3##\ betaine ðBet\ ¦ − ¦ − "CH2#2N CH1CO1 Ł\ and trimethylamine N!oxide ðTMAO\ "CH2#2N O Ł were also reported as active substances of turbot\ plaice\ or Dover sole "Table 1#[ 307 Marine Natural Products and Marine Chemical Ecolo`y Table 1 Feeding attractants and stimulants of _sh[ *ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Predator _sh Prey animals Active substances Ref[ *ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ Bathystoma rimator Arca zevra arcamine "0#21 Bathystoma rimator Strombus `i`as strombine "1#21 Merlan`ius merlan`us Arenicola marina Gly\ Ala\ Ser\ Thr\ Leu\ Glu\ Val 16\ 22 Chrysophrys major Perinereis vancaurica tetradentata Gly\ Ala\ Val\ amphoteric ~uorescent substance 23 La`odon rhomboides Penacus duorarum Gly\ Asp\ Ile\ Phe\ Bet 16 Salmo `airdnerii Gly\ Ala\ a!Aba\a Val 24 Scophthalmus maximus squid extract 4?!IMP\ inosine 25 Pleuronectes platessa squid extract amino acids\ AMP\ TMAO 26 Limanda limanda squid extract amino acids 26 Soleo solea Mytilus edulis Bet 16 *ÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐÐ