Marine Natural Products 1999

Marine natural productsD. John FaulknerScripps Institution of Oceanography, University of California at San Diego, La Jolla, CA 92093-0212, USAReceived (in Cambridge) 17th September 1998 Covering: 1997Previous review: 1998, 15, 1131Introduction2Marine microorganisms and phytoplankton3Green algae4Brown algae5Red algae6Sponges7Coelenterates8Bryozoans9Molluscs10Tunicates (ascidians)11Echinoderms12Miscellaneous13References1IntroductionThis Report is a review of the literature of marine natural product chemistry for 1997. Earlier reports published in this journal cover the period from 1977 to December 1996. The most striking change in the direction of marine natural product chemistry during 1997 was reflected in the sudden increase in reports of new metabolites from marine microorganisms, although the general level of activity in describing new marine natural products declined very slightly for the first time. Sponge metabolites continue to dominate the reports of new compounds but there is an increasing interest in the possibility that some of these metabolites are produced by associated microorganisms. In addition, more marine natural products are being selected for synthesis and for in-depth investigations of their biological properties, both from the biomedical and ecological (biofoul-ing) viewpoints. The overall picture is that marine natural product chemistry remains a vigorous scientific discipline with ample room to expand its influence.The format for this review is identical to that of its immediate predecessors. The review does not provide a comprehensive coverage of all research involving chemicals from marine organisms but concentrates on reports of novel marine natural products with interesting biological and pharmaceutical proper-ties. Biochemical studies involving marine organisms, studies of the biosynthesis of marine natural products and reports of primary metabolites are specifically omitted. Wherever possi-ble, the biological and pharmacological properties of new marine natural products have been reported but papers detailing the pharmacological studies are considered to be beyond the scope of this review. In the area of synthetic organic chemistry, the review focusses on reports of the total synthesis of marine natural products that confirm or redefine chemical structures. No attempt has been made to review the patent literature or conference abstracts, although experience has shown that these are very important sources for those seeking new structures for synthesis.The majority of the reviews featuring marine natural products chemistry that were published during 1997 are clustered in a few topical areas of interest. Marine microbiology is well represented with reviews on ‘Secondary metabolites from marine microorganisms—bacteria, protozoa, algae and fungi—achievements and prospects’,1‘Marine microorganisms as a source of new natural products’2and ‘Amphidinolides: unique macrolides from marine dinoflagellates’.3Marine chemical ecology has been reviewed from the viewpoint of its effects on community structure in ‘A review of the chemical ecology of Antarctic marine invertebrates’4and its role in influencing biofouling in ‘Development of chemical substances regulating biofilm formation’5and ‘Marine natural products influencing larval settlement and metamorphosis of benthic invertebrates’.6 Specific classes of compounds are evaluated in ‘New per-spectives in the chemistry and biochemistry of the tunichromes and related compounds’,7‘Synthetic studies on polypropionate-derived 4-pyrone-containing marine natural products’,8‘Struc-tures and biogenesis of manzamines and related compounds’9 and ‘Alkylpyridine alkaloids from marine sponges’.10Other topics reviewed are ‘Bioactive compounds from the sea hares of two genera, Aplysia and Dolabella’,11‘Marine natural products as prototype insecticidal agents’,12‘Chemical constituents of the soft coral species of Sarcophyton genus: a review’,13‘Toxins from the starfish Acanthaster planci and Asterina pectinifera’14and ‘Interesting bioactive compounds from marine organisms’.15A multidisciplinary treatise on sponges, which is the proceedings of a meeting at Lake Biwa in Japan, contains many contributions of interest to natural product chemists.162Marine microorganisms and phytoplanktonIt is not easy to define “marine” bacteria and fungi because many isolates will tolerate quite a wide range of salinities. Bacteria and fungi found in coastal waters may have been washed into the ocean from rivers, estuaries and sewage outfalls. For these reasons, it is probably best to adopt a pragmatic definition of marine microorganisms as those isolated on seawater media from marine organisms and sediments but one should not be too surprised if some of their metabolites are very similar to those from terrestrial micro-organisms. Pseudoalteromonas sp. F-420 was isolated from the surface of the green alga Halimeda sp. from Palau and was grown on 75% artificial seawater to obtain korormicin 1, which inhibited the growth of marine bacteria but did not affect terrestrial species.17A seawater isolate, Cytophaga sp. SANK 71996, produced a series of N-(3-acyloxyacyl)glycines 2–4that were shown to be N-type calcium channel blockers.18The otherwise inseparable mixture of N-(3-acyloxyacyl)glycines was converted into the corresponding benzhydryl esters, which were separated and the purified esters hydrolysed to obtain the novel N-(3-acyloxyacyl)glycines 2and 3, together with the known metabolite 4that had previously been obtained from the gliding bacterium Cytophaga johnsone.19A marine Strepto-myces sp. (strain B 8300) from a lagoon on the Gulf of Mexico contained a new pluramycin-class antibiotic, d-indomycinone 5, together with the known20metabolite b-indomycinone.21A new isocoumarin antitumour agent known as PM-94128 6was obtained from the culture broth of Bacillus sp. PhM-PHD-090 that had been isolated from a marine sediment.22Four additional minor antimicrobial agents, thiomarinols D - G 7–10, have been obtained from Alteromonas rava sp. nov. SANK 73390.23The marine bacterium Micrococcus luteus, isolated from a suspension of cells from a New Caledonian sponge of theNat. Prod. Rep., 1999, 16, 155–198155genus Xestospongia, produced the glycolipid lutoside 11.24Actinoflavoside 12is a flavanoid-like glycoside from aStreptomyces sp. isolated from an estuarine sediment in NewZealand.25Octalactin A 13, which is a metabolite of a marineStreptomyces sp.,26has been formally synthesized in anenantioselective manner.27Both the ascidian Stomozoa murrayi and an associatedbacterium Acinetobacter sp. contained 6-bromoindole-3-carbal-dehyde 14, which had previously been isolated from a marinePseudomonas sp.286-Bromoindole-3-carbaldehyde 14inhib-ited in vitro settlement of barnacle (Balanus amphitrite) larvaeand showed moderate antibacterial properties.29Three newanticancer antibiotics of the phenazine class, pelagiomicins A–C 15–17, together with the known metabolite griseoluteic acid18,30were obtained from the Gram-negative bacterium Pela-giobacter variabilis that was isolated from a Palauan macro algaPocockiella variegata.31Pelagiomicin A 15(LL-14I352a) andgriseoluteic acid 18(LL-14I352b) were also obtained from anew halophilic marine bacterium (LL-14I352) that was isolatedfrom an unidentified orange tunicate from Fiji. Both phenazines15and 18exhibited activity in a BIA assay to detect DNAdamaging agents.32A marine Streptomyces sp. (strain B 8251)isolated from a marine sediment sample from the Gulf ofMexico contained the weakly antimicrobial alkaloid dihy-drophencomycin methyl ester 19, together with several knownmetabolites.33Hydroxyakalone 20is a new xanthine oxidaseinhibitor from the fermentation broth of the marine bacteriumAgrobacterium aurantiacum N-81106.34An unusual medium-ring bis-amide, bahamamide 21, was obtained from the culturebroth of an undescribed marine bacterium (CNE-852) that hadbeen isolated from a marine sediment from Cat Island in theBahamas.35Four mildly cytotoxic acyldepsipeptides, kailuinsA–D 22–25, were isolated from liquid cultures of a Gram-negative bacterium (BH-107) obtained from driftwood col-lected at Kailua beach, Oahu.36The antimicrobial agentsmassetolides A–H 26–33are closely related cyclic depsipep-156Nat. Prod. Rep., 1999, 16, 155–198tides that were isolated from lawn cultures of two Pseudomonasspecies, MK90e85 and MK91CC8, that were obtained from anunidentified red alga and an unidentified tube-worm, re-spectively, both of which were collected in British Colum-bia.37A strain of the fungus Periconia byssoides that had originallybeen isolated from the gastrointestinal tract of the sea hareAplysia kurodai produced two cytotoxic triols, pericosides A 34and B 35, and four new macrolides, macrosphelides E–H36–39.38A Pithomyces sp. obtained from the Indo-Pacifictunicate Oxycorynia fascicularis contained four new polyketidepigments, pitholides A–D 40–43.39Insulicolide 44is anitrobenzoyloxy-substituted sesquiterpene from Aspergillusinsulicola that had been obtained from various algae from theBahamas.40Gymnastatins A–C 45–47, which were produced bya strain of Gymnascella dankaliensis isolated from the spongeHalichondria japonica, showed significant cytotoxicity againsttumour cell lines.41A saltwater culture of Aspergillus nigerderived from the sponge Hyrtios proteus from Florida produceda cytotoxic dimeric diketopiperazine alkaloid, asperazine 48.42Thiocoraline 49is an interesting bicyclic peptide with anti-tumour activity that was obtained from the mycelium of amarine Micromonospora sp. L-13-ACM2-092.43The cytotoxicagent acetophthalidin 50, which was isolated from the marineNat. Prod. Rep., 1999, 16, 155–198157fungus Penicillium sp. BM923,44has been synthesized in astraightforward manner.45An enantiospecific total synthesis oftryprostatin A 51, which is a cytotoxic diketopiperazine fromAspergillus fumigatus strain BM939,46employed a newregiospecific bromination procedure.47,48The marine sedimentorigin of A. fumigatus, which also produced tryprostatin B 52,had not previously been noted in these reports and a previoussynthesis of tryprostatin B49had also been omitted.Research on the chemistry of cyanobacteria (blue-greenalgae) continues to be concentrated within a limited number ofspecies. A specimen of Lyngbya bouillonii from Papua NewGuinea contained the novel macrolide lyngbyaloside 53, thestereochemistry of which was only partially determined.50Malyngamides J–L 54–56are three additional ichthyotoxic andbrine-shrimp toxic metabolites that were isolated from acollection of L. majuscula from Curaçao.51The same specimenof L. majuscula also contained two quinoline alkaloids 57and58 as minor metabolites.52A mixed collection of L. majusculaand a Microcoleus sp. found growing on the hard coral Poritescylindrica at Guam contained the chlorolipid pitiamide A 59.53The determination of absolute stereochemistry54and two totalsyntheses54,55of the cytotoxic agent (+)-curacin A 60, whichwas obtained from a specimen of L. majuscula from Curaçao,56were reported. Two new stereocontrolled syntheses of (2)-ma-lyngolide 61, which is an antimicrobial agent from Lyngbyamajuscula,57use very different strategies to induce asym-metry.58,59Nakienone A 62, a metabolite of a cyanophyte of thegenus Synechocystis from Okinawa,60has been synthesizedusing a palladium-catalyzed coupling reaction.61An additionalsynthesis of the alkaloid hyellazole 63, which is a metabolite ofHyella caespitosa,62has been described as one example of ageneral route to carbazoles.63Continued studies of the dinoflagellate Amphidinium sp.(strain Y-5), which was a symbiont of an Okinawan flatwormAmphiscolops sp.,3resulted in the isolation of two additionalcytotoxic 14-membered macrolides, amphidinolides R 64and S65.64A different strain of Amphidinium sp. (strain Y-52) fromthe flatworm Pseudaphanostoma luteocoloris produced luteo-158Nat. Prod. Rep., 1999, 16, 155–198phanol A 66, which showed only weak antimicrobial activity.65Amphidinols 5 67and 6 68are additional polyhydroxy polyenes from Amphidinium klebsii that disrupt cholesterol-containing lipid membranes.66The absolute stereochemistry of gymnodi-mine 69, which is a neurotoxin produced by a Gymnodinium sp.that gave rise to neurotoxic shellfish poisoning in New Zealand oysters,67has been determined by X-ray analysis of a p -bromobenzoyl derivative of the reduced imine gymnodamine.68The dinoflagellate Protoceratium reticulatum has been identi-fied as the dietary source of yessotoxin 70,which is the causative agent of diarrhetic shellfish poisoning in the New Zealand greenshell mussel Perna canaliculus .69The marine diatom Pseudo-nitzschia multiseries (strain S2-184-1) excretes the eicosanoid-derived metabolite bacillariolide III 71.70Raiko-venal 72and preraikovenal 73, which are metabolites of the marine ciliate Euplotes raikovi ,71have been synthesized as racemates.723Green algaeA new cycloartenol sulfate 74, which is an inhibitor of VZV and CMV proteases, was isolated from a Tuemoya sp. from an unspecified location.73Sulfonoquinovosyl dipalmitoyl glycer-ide 75is a P-selectrin receptor inhibitor from Dictyochloris fragrans , also from an unspecified location.74A new bisindole alkaloid, caulersin 76, was isolated from Caulerpa serrulata from the South China Sea.75Sertularamide 77is a new ceramide from C. sertularioides 76and a -1-glyceryl-d -mannoside-4-am-monium salt 78was found in Cologlossa leprieurii , which is a traditional Chinese drug used as an anthelmintic.774Brown algaeA very careful reexamination of the sexual reproduction of Ectocarpus siliculosus using synthetic pheromones revealed that the true chemical attractant produced by female gametes was the unstable cis -cyclopropane pre-ectocarpene 79, which rapidly (t 1/2= 21 min at 18°C) underwent a Cope rearrange-ment to produce ectocarpene 80.78The absolute configuration of (3S ,4S )-3-n -butyl-4-vinylcyclopentene 81from Dictyopteris prolifera from Japan was determined by synthesis of both the optical enantiomer and the racemate.79The chemoenzymatic synthesis of a key intermediate allowed the enantio- and stereospecific syntheses of (+)-(3S ,4S )-3-n -butyl-4-vinylcyclo-pentene 81, (+)-(Z )-(3S ,4S )-multifidene 82,80(+)-(E )-(3S ,4S )-multifidene 83,81(+)-(3S ,4R )-viridiene 84,82and (+)-(Z )-Nat. Prod. Rep., 1999, 16, 155–198159(2R,3R,1’S,5’S)-caudoxirene 85,83all of which are constituentsof various brown algal pheromones.84The racemate oflamiroxene 86, which is a gamete-releasing and gamete-attracting pheromone of Laminaria digitata,85has been synthe-sized in 25% overall yield.86The syntheses of the triene 87, bis-epoxide 88, and dihydroxytetrahydrofurans 89and 90, all ofwhich are metabolites of Notheia anomola,87,88follow thepresumed biomimetic sequence.89The absolute configuration of (+)-sporochnol A 91, which isa fish deterrent from Sporochnus bolleanus,90was determinedby total synthesis of the enantiomer from (S)-epichlorohydrin.91Five new dolabellane diterpenes, (1R,2E,4S,5R,6S,7E,10S,11S,12R)-5,6,18-triacetoxy-10-hydroxy-2,7-dolabelladiene 92,(1R,2E,4R,7E,10S,11S,12R)-18-acetoxy-10-hydroxy-2,7-dola-belladiene 93, (1R,2E,4S,5R,7E,10S,11S,12R)-5-acetoxy-10,18-dihydroxy-2,7-dolabelladiene 94, (1R*,3E,7S*,8S*,11S*,12R*)-7,8-epoxy-3,18-dolabelladiene 95, and (1R*,2E,4R*,7E,11S*,12R*)-18-acetoxy-dolabelladiene 96, togetherwith two hydroazulene diterpenes, isopachydictyol A 97anddictyotatriol A 98, were isolated as mildly cytotoxic con-stituents of Dictyota dichotoma from Cádiz, Spain.92(+)-Tao-nianone 99, which is a metabolite of Taonia australasica,93wassynthesized in a convergent, enantioselective manner.94Twosyntheses of the diterpene (+)-epoxydictymene 100, which is aditerpene with two trans-fused five-membered rings from D.dichotoma,95present contrasting synthetic strategies.96298Turbinaria ornata from Formosa contained the new sterolhydroperoxide 29-hydroperoxystigmasta-5,24(28)-dien-3b-ol101.99The chromenols 102and 103were obtained, togetherwith several known meroditerpenoids, from Desmarestiamenziesii from King George Island in the Antarctic.100Twonew meroditerpenoids 104and 105were obtained fromCystoseira amentacea var. stricta from the French Riviera and 160Nat. Prod. Rep., 1999, 16, 155–198a third meroditerpenoid 106was isolated from a specimen of thesame alga from the Galite Islands, Tunisia.101The absoluteconfigurations of seven meroditerpenoids 107–113from Cysto-seira species were determined using the modified Mosher’smethod and were used to support proposed biosyntheticrelationships within the series of metabolites.102A number of phloroglucinols have been isolated as theirperacetyl derivatives but one cannot help wondering whether itcan be assumed that all of the deacetylated compounds wereactually natural products. This is particularly true of phloro-scorbinol hexaacetate 114that was isolated from Sargassumspinuligerum.103A new group of pseudofuhalol peracetates,exemplified by the simplest member of the series, pseudo-trifuhalol-A octaacetate 115, have been obtained from S.spinuligerum,104and some additional fucophlorethol per-acetates, which include chlorobisfucopentaphlorethol-A non-adecaacetate 116, have been isolated from S. spinuligerum andCystophora torulosa,105the latter being the source of a total of33 phlorotannins, 13 of which were recently described.106Theabsolute configuration of 17(R)-hydroxyeicosatetraenoyl-phloroglucinol 117, which is a major component of Zonaria-diesingiana from Japan but which was first described in1982,107was determined by a degradative strategy.1085Red algaeThe stereochemistry of yendolipin 118, which is a metabolite ofNeodilsea yendoana that inhibits morphogenesis in the folia-ceous green alga Monostroma oxyspermum,109has been revisedfrom (3A S) to (3A R).110An unusual iodolactone 119has beenisolated from a specimen of Laurencia majuscula from theXisha Islands in the South China Sea.111Laurencione 120,which is a major metabolite of L. spectablilis,112has beensynthesized in one step from 5-hydroxypentan-2-one.1132-Ace-tyl-1,1-dibromoheptane 121and 3-acetyl-1,1,2-tribromooct-1-ene 122were isolated as minor metabolites of Deliseafimbriata from the Antarctic.114Unexpected food poisoningsresulting from ingestion of Gracilaria coronopifolia in Hawaiiwere traced to a seasonal production of manauealides A 123, B124and C 125, and the known toxins, aplysiatoxin 126andNat. Prod. Rep., 1999, 16, 155–198161debromoaplysiatoxin 127, which are normally115associatedwith the cyanophyte Lyngbya majuscula.116The twelve-membered cyclic ether obtusallene IV 128, whichis a C15acetogenin from Laurencia obtusa from the TurkishMediterranean, is among several similar cyclic ethers that existin solution as slowly interconverting conformers resulting froma ‘crankshaft’ motion of the trans olefinic bond.117Scanlone-nyne 129is a halogenated acetogenin from a specimen of L.obtusa from Scanlon’s Island, Ireland.118L. claviformis, aspecies endemic to Easter Island, contained five knowncompounds together with the new C15acetogenin (3Z)-13-epipinnatifidenyne 130.119The structure and stereochem-istry of (+)-isolaurepinnacin 131, which is a metabolite of L.pinnata,120have been confirmed by total synthesis.121Abiomimetic type synthesis of trans-desacetylkumausyne 132, ametabolite of L. nipponica,122involved bromonium-ion in-duced cyclization123and (2)-trans-kumausyne 133was synthe-sized from d-(+)-xylose.124Both enzymatic and chemicalbromo-etherification reactions were employed in the conver-sion of prelaureatin 134into laurallene 135,125both of whichoccur in L. nipponica.126,127A formal synthesis of (+)-laurencin136, which is a metabolite of L. glandulifera,128has also beendescribed.129Although no new halogenated monoterpenes were reportedduring 1997, these small molecules continue to provide asynthetic challenge. Two cytotoxic monoterpenes 137and 138 162Nat. Prod. Rep., 1999, 16, 155–198from Portieria hornemanni,130have been synthesized asracemates.131The cyclic monoterpene 139from the Australianalga Plocamium hamatum132has been synthesized using aDiels–Alder strategy that employed a bridgehead allylsilane toaccomplish stereospecific chlorination.133Majusin 140is ahalogenated cedrene-type sesquiterpene from Laurencia ma-juscula collected at the Xisha Islands in the South China Sea.134The antimicrobial activity of a specimen of L. obtusa fromDominica was shown to be due to allolaurineterol 141.135Debromoisolaurinterol 142and two chamigrane-type sesqui-terpenes 143 and 144that had previously been reported onlyfrom the sea hare Aplysia dactylomela136were encounteredduring a comparative study of two ‘chemical races’ of L.majuscula from Japan.137An antifouling dichloromethaneextract of L. rigida from Australia contained four newmetabolites, 3-acetoxy-E-g-bisabolene 145, (2)-10a-bromo-9b-hydroxy-a-chamigrene 146, rigidol 147, and (+)-(10S)-10-bromo-b-chamigrene 148, all of which partially contributeto the antifouling properties of the extract.138The nor-chamigrane ma’ilione 149and allo-isoobtusol 150wereobtained from L. cartilaginea from Hawaii.139The structureproposed for allo-isoobtusol 150was subsequently challengedon the basis of a chemotaxonomic study that related certainstereochemical features of chamigranes with various Laurenciaspecies. It was suggested on the basis of the reported 13C NMRdata139that the positions of the halogen atoms on ring B of‘allo-isoobtusol’ be reversed, thereby rendering the nameincorrect, and that the revised structure be called cartilagineol151.140Thus, adding further confusion to an already complexsituation,141allo-isoobtusol 150should no longer exist andinstead becomes cartilagineol 151. Laurene 152, which is ametabolite of L. glandulifera,142has been synthesized in anefficient manner but without any stereochemical control.143Oppositol 153, which is a metabolite of Laurencia sub-opposita,144has been synthesized as the racemate in astereoselective manner.145Paniculatol 154, the structure of which was determined by X-ray crystallography, is a new ent-labdane diterpene fromLaurencia paniculata from the Qatari coast of the ArabianGulf.146The structures of rogioldiol A 155, which is a diterpeneproduced by L. microcladia from Il Rogiolo, and a degradationproduct, rogiolal156, were elucidated using a combination ofX-ray crystallography and spectroscopic methods.147Twomildly cytotoxic brominated triterpenoids, thyrsenols A 157and B158, were isolated from L. viridis from the CanaryIslands and their structures were elucidated by interpretation ofspectroscopic data.148Subsequently, five additional brominatedtriterpenoids, dehydrovenustatriol 159, 15,16-dehydrovenusta-triol 160, predehydrovenustatriol acetate 161, 16-hydroxydehy-drothyrsiferiol 162, and 10-epi-15,16-dehydrothyrsiferiol 163,were described from the same specimens of L. viridis.149Fourcytotoxic sterol hydroperoxides 164–167were isolated fromGalaxaura marginata collected at Taiwan.150Isodomoic acids G 168and H 169, which are two newisomers of the neurotoxin domoic acid, were isolated fromJapanese Chondria armata and identified by interpretation ofspectral data.151(2)-Kainic acid 170, which is an anthelminticand neuroexcitatory agent from Digenea simplex,152has beensynthesized in an enantiocontrolled manner from (+)-norcam-phor,153and by two different enantioselective syntheses thatinvolve free radical cyclization.154,155The major arseniccompound in the edible alga Chondria crassicaulis(yuna) wasfound to be 1-deoxy-1-dimethylarsinoylribitol-5-sulfate 171,which was synthesized from ribitol.156Nat. Prod. Rep., 1999, 16, 155–1981636SpongesSponges (Porifera) continue to be the most actively studiedmarine phylum. As can be deduced from the section on marinemicroorganisms, they are also a prominent source of associatedbacteria and fungi. However, the number of sponge metabolitesthat have been shown to be produced by microorganisms is verysmall compared with the number attributed to symbioticsources. An increasing number of unusual lipids have beendescribed from sponges. Amphimic acids A 172, B 173and C174, from an Australian Amphimedon sp., are unusual long-chained fatty acids that contain a methylene cyclopropanemoiety.157,158Amphimic acids A 172and C 174and some co-occurring (5Z, 9Z) long chained (C27and C28) fatty acids inhibithuman DNA topoisomerase I at micromolar concentrations.Both amphimic acid A 172and its (9Z) isomer have beensynthesized as racemates.158Hanishenols A 175and B 176areunusual glycerol enol ethers from a specimen of Acanthellacarteri from the Hanish Islands, Yemen.159The cytotoxiccomponent of Spongia cf.hispida from Singapore is spongilipid177, which shows selective inhibition of the fecal opportunistEnterococcus faecalis.160The ketonic lipid, (6Z,9Z,12Z,15Z)-octadeca-1,6,9,12,15-penten-3-one 178, has been isolated to-gether with the corresponding acid, (4Z,7Z,10Z,13Z)-hexadeca-4,7,10,13-tetraenoic acid, from a Callyspongia sp. fromAustralia.161The Mediterranean sponge Reniera mucosa con-tained the bicyclic eicosanoid mucosin 179.162Halicholactone180and neohalicholactone 181, which are fatty acid derivativesfrom Halichondria okadai,163have been synthesized by anenantioselective route.164Perhaps the most unusual lipid to bedescribed from a sponge is poecillanosine 182, which is a freeradical scavenger isolated from Poecillastra spec. aff. tenuila-minaris.165Plakosides A 183and B 184, which exhibitimmunosuppressive properties, are prenylated glycosphingo-lipids from the Bahamian sponge Plakortis simplex.166Theabsolute stereochemistry of chondrillin 185, which is a cyclicperoxide from Chondrilla sp.167and Plakortis lita,168has beenrevised from 186on the basis of enantioselective syntheses ofboth plakorin 187, which was isolated from an OkinawanPlakortis sp.,169and ent-chondrillin 186.170Callystatin A 188is a potent cytotoxin that was isolated as aminor metabolite from Callyspongia truncata from Japan.171It 164Nat. Prod. Rep., 1999, 16, 155–198may be significant that callystatin A 188was also isolated froma Stelletta sp. and an unidentified ascidian from the samelocation. The complete absolute stereostructure of callystatin A188was determined by application of Mosher’s method171andby comparing the CD spectrum with that of two modelcompounds.172Another specimen of Callyspongia truncatafrom Japan contained the acetylenic hydrocarbons callytetrayne189and callypentayne 190, together with five triols, callytriolsA–E 191–195. All seven acetylenes induce metamorphosis inlarvae of the ascidian Halocynthia roretzi and the triols alsoshowed antifouling activity against the barnacle Balanusamphitrite.173The same acteylenic hydrocarbons, callytetrayne189and callypentayne 190, together with a third hydrocarboncallyberyne 196were isolated from a Callyspongia sp., againfrom Japan.174Pellynic acid 197, which inhibited inosinemonophosphate dehydrogenase in vitro, pellynols A–D198–201and pellynone 202were obtained from Pellinatriangulata from Chuuk (Truk) Atoll.175The positioning of theketone group in pellynone 202was tentatively assigned.175Taurospongin A 203is an unusual acetylenic fatty acidderivative from an Okinawan Hippospongia sp. that inhibitsboth DNA polymerase b and HIV reverse transcriptase.176BRS1 204, which inhibits protein kinase C, is a amino-lipidfrom an unidentified Australian calcareous sponge.177Thecalcareous sponge Leucetta leptorhaphis from the Antarcticcontained the cytotoxic component rhapsamine 205.178Threesynthetic routes to penaresidins A 206and B 207, which areazetidine-containing alkaloids from Penares sp.,179have beenreported together with the syntheses of several stereo-isomers.180–182Four new N-acyl-2-methylene-b-alanine methylesters, hurghamides A–D 208–211were isolated from aHippospongia sp. from the Red Sea.183A Spanish specimen ofNat. Prod. Rep., 1999, 16, 155–198165。