Angelo Fontana

A new antitumor isoquinoline alkaloid from the marine nudibranch Jorunna funebris

Abstract A new dimeric isoquinoline alkaloid, jorumycin (3), has been isolated from the skin and the mucus of the Pacific nudibranch Jorunna funebris. The structure has been fully elucidated on the grounds of ESMS data and of an extensive 2D NMR analysis. The cytotoxicity of 3 was evaluated against various human cancer cell lines and was found to be slightly less potent than Et 743 (2).

Chemical ecology of the Antarctic nudibranch Bathydoris hodgsoni Eliot, 1907: defensive role and origin of its natural products.

A variety of Antarctic marine invertebrates contains secondary metabolites that may provide defense against potential predators. However, only in a few cases have tissues, extracts or isolated compounds of these invertebrates been tested against sympatric predators. The Antarctic nudibranch Bathydoris hodgsoni Eliot, 1907 contains hodgsonal, a compound only present in the external body (mantle tissues), which may protect the slugs from predators. To test this defensive hypothesis for hodgsonal, we carried out a series of experiments using the sympatric omnivorous seastar Odontaster validus Koehler, 1906 as a potential predator. Our experiments revealed that natural concentrations of hodgsonal elicit significant feeding deterrent responses in O. validus. Furthermore, hodgsonal is probably biosynthesized de novo by the nudibranch, since it was not detected in the viscera (as it should be in the case of a dietary compound), its concentration in the mantle (0.05-0.15% dry mass) is quite constant in individuals from different localities and depths, and its sequestration from a particular dietary source is unlikely because B. hodgsoni is an omnivorous feeder.

Transfer of secondary metabolites from the spongesDysidea fragilis andPleraplysilla spinifera to the mantle dermal formations (MDFs) of the mudibranchHypserlodoris webbi

The opisthobranch molluscHypselodoris webbi is able to select, among its potential preys, sponges chemically rich in furanosesquiterpenoids. The sequestered secondary metabolites act as defensive allomones against predators and are accumulated in some dorsal glands (MDFs). This transfer from sponges to MDFs has been proven by maintainingH. webbi together with some selected sponges in an aquarium for a prolonged period.

Defensive strategy of twoHypselodoris nudibranchs from Italian and Spanish coasts

Hypselodoris nudibranchs from different geographic areas (Spain and Italy) have been studied in order to investigate their general defensive strategy. Longifolin (1) and nakafuran-9 (2) are the main ichthyodeterrent allomones used by the mollusks to avoid predation. Evidence of their dietary origin is presented and the very effective strategy against predators, which includes secretion of allomones into the mucus and their storage into specific mantle dermal formations (MDFs), is also discussed.

Defensive allomones in three species ofHypselodoris (gastropoda: Nudibranchia) from the Cantabrian sea.

ThreeHypselodoris species,H. villafranca, H. cantabrica, and H. tricolor, have been studied in order to further investigate the defensive strategies of Chromodorididae mollusks from Iberian coasts. All animals possess large amounts of furanosesquiterpenoids, probably derived from their diet of sponges. The products are transferred and stored in specific sites of the mantle (mantle dermal formations, MDFs) to be used as chemical deterrents against predators. Chemical analysis of CantabrianHypselodoris species has led to the characterization of eight sesquiterpenoids. Among these, six have been found previously in both sponges and nudibranchs, while two are new natural products.Hypselodoris species cooccurring in the same area contained comparable mixtures of sesquiterpenoids. However, two populations ofH. cantabrica from different sites of the Cantabrian sea showed different metabolic patterns. All sesquiterpenoids induce feeding deterrence inCarassius auratus and two are also toxic toGambusia affinis.

Biotransformation of a dietary sesterterpenoid in the Mediterranean nudibranchHypselodoris orsini

The metabolic relationship between the marine molluscHypselodoris orsini and the spongeCacospongia mollior has been reinvestigated. The predator-prey association has been confirmed even though the metabolic patterns of the two invertebrates are substantially different. Most probably the nudibranch converts the main sponge metabolite, the sesterterpenoid scalaradial (1), into a less oxygenated related metabolite, deoxoscalarin (4), followed by a second chemical transformation leading to a new sesterterpenoid, 6-keto-deoxoscalarin (5) which is selectively compartmentalized into some dorsal glands, mantle dermal formations (MDFs), strategically distributed near the gills. 6-keto-deoxoscalarin (5) has been characterized by 1D and 2D NMR methods. Finally, the unusual association of some Chromodorididae molluscs with sponges containing sesterterpenoids suggests a further analysis of their taxonomical collocation is required.

Structures and absolute stereochemistry of isocyanide and isothiocyanate amphilectenes from the Caribbean sponge Cribochalina sp.

Abstract Three new diterpenes (5–7), based on amphilectene skeleton, were isolated from the Caribbean sponge Cribochalina sp.. All contain isocyanide and isothiocyanate functions and are epimers at C-7 of previously characterized diterpenoids. The structures of 5–7 were established by spectroscopic techniques. The sponge extract also showed the presence of the known metabolite 4, together with the new bicyclic diterpene 8, potential precursor of the co-occurring amphilectenes. For the first time, the absolute configuration of the amphilectene skeleton has been assigned by applying the modified Moshers method on a derivative of the main compound 4. The isocyanide 4 reduced the proliferation of lymphocytes T and B under various stimuli.

HODGSONAL, A NEW DRIMANE SESQUITERPENE FROM THE MANTLE OF THE ANTARCTIC NUDIBRANCH BATHYDORIS HODGSONI

Abstract A new drimane sesquiterpene, hodgsonal ( 1 ), has been isolated from the mantle extract of the Antarctic opisthobranch mollusc Bathydoris hodgsoni . The structure of 1 , including the absolute stereochemistry, has been elucidated by spectroscopic and chemical methods. The localization of 1 in the mantle and the analogies with related drimane compounds may indicate a defensive role against predators.

Terpene biosynthesis in marine molluscs: incorporation of glucose in drimane esters of Dendrodoris nudibranchs via classical mevalonate pathway

Abstract The biosynthesis of drimane esters in marine molluscs Dendrodoris limbata and Dendrodoris grandiflora has been reinvestigated by feeding experiments with d -[ 14 C-(U)]- and d -[6- 13 C]-glucose. Both experiments proved the incorporation of the precursors in the terpenoid part of drimane esters. Use of [6- 13 C]-glucose also demonstrated that the labelled material was incorporated via the classical acetate/mevalonate pathway.

Absolute stereochemistry of natural sesquiterpenoid diacylglycerols

Abstract The absolute stereochemistry of farnesic and drimenic glyceryl esters 1a – 1c and 2a – 2b , previously isolated from marine dorid nudibranchs, has been established by their synthesis.