Secondary metabolites of the Vietnamese nudibranch mollusk Phyllidiella pustulosa

Abstract

A. I. Kalinovskii, and V. A. StonikThe chemical composition of the EtOH extract of the nudibranch mollusk Phyllidiella pustulosa was studied. Six sesquiterpenoids including the novel secondary metabolite (+)-10(R)-isothiocyanoalloaromodendrane were isolated. The steroid composition of the extract was studied. The structures of three previously known ketosteroids and six sterols were identified.Nudibranch mollusks of the family Phyllidiidae are commonly known to be sources of various toxic sesquiterpenoids containing cyanate, isocyanate, thiocyanate, and isothiocyanate groups [1]. Secondary metabolites from populations of these animals collected along the shores of China [2], Fiji [3], the Philippines [4], Japan [5-9], and Australia [10] have been previously studied. These soft mollusks lack shells and feed on sponges. They use certain compounds ingested with their food for chemical protection against predators. Several compounds isolated from them exhibit various types of biological activity in addition to a deterrant action. These include antimicrobial [11], antifouling [9], antifungal [5], and antimalarial [3]. The qualitative and quantitative contents of secondary metabolites in extracts of nudibranch mollusks are known to depend on the time, site, and food source of the animals [1,12].Seven sesquiterpenoids including the new isothiocyanate 1 were isolated by chromatographic methods from the extract of Phyllidiella pustulosa collected during cruise O34 of RS Akademik Oparin off the shores of Vietnam.The structure and stereochemistry of 1 were determined by PMR and 13 C NMR spectroscopy (including NOESY, HMBC, and HMQC experiments), mass spectrometry, and comparision of the results with the literature. NMR spectra of 1 were identical to those of the previously known semisynthetic (-)-1S,4R,5R,6S,7R,10S-isothiocyanoalloaromadendrane [13]. However, its optical rotation [D] D 20 +6.0° (c 0.15, CHCl 3 ) turned out to be close but opposite in sign to that of (-)-alloaromadendrane {[D] D 20 -5.9° (c 2.10, CHCl 3 )}. Therefore, 1 had the absolute configuration 1R,4S,5S,6R,7S,10R and was an enantiomer of the synthetic product.In addition to 1, we isolated and identified the structures of previously known sesquiterpenoids. The major metabolite was the isocyanate 2; a minor one, isothiocyanate 3, which is related to it. Both metabolites were found earlier in the sponge Acanthella acuta [14]. The inseparable mixture of 4a-4b (1:1) obtained by us turned out to be identical to a mixture of these Pacific Institute of Bioorganic Chemistry, Far-East Branch, Russian Academy of Sciences, 690022, Vladivostok, Russia, fax 7(4232) 31 40 50,

Terpenoids in Marine Heterobranch Molluscs

“…These diterpene isonitriles are kalihinene, amphilectene (48), kalihinol-A (49), and kalihinol-E ( Figure 7). P. pustulosa from Vietnam also contains these compounds and some sterols [129]. Three isonitriles, pustulosaisonitriles-1 (50), -2, and -3 ( Figure 7) are also found in P. pustulosa from Australia, with pustulosaisonitrile-1 exhibiting moderate levels of antimalarial activity in vitro [188].…”

“…One of the most studied species is Phyllidiella pustulosa, where compounds are obtained from the demosponge Acanthella cavernosa [126]. Specimens from China and Vietnam also contain sesquiterpene isocyanides and related compounds, some of them found also in Acanthella sponges [126][127][128][129]. A recent chemical analyses of the South China Sea nudibranchs Phyllidiella pustulosa and Phyllidia coelestis, as well as their possible sponge prey Acanthella cavernosa, led to the isolation of a nitrogenous cadinane-type sesquiterpenoid, xidaoisocyanate A (24) ( Figure 4), among other sesquiterpenoids and diterpenoids [130].…”

A new bioactive steroidal ketone from the South China Sea sponge Xestospongia testudinaria

“…Up to now, steroids bearing an ergosta-22,25-diene side chain have been reported from the nudibranch mollusks Phyllidia varicosa [15] and Phyllidiella pustulosa [16], from soft coral Sarcophyton sp. [14,17] and from sponges Pseudaxinella lunacharta [18], Biemna sp.…”

Achievements in the Study of Marine Low‐Molecular Weight Biologically Active Metabolites from the Vietnamese Territorial Waters as a Result of Expeditions aboard the Research Vessel ‘Akademik Oparin’ (2004–2017)

“…The steroid composition of the extract was also studied, and three known ketosteroids 20-22 and six sterols 23-28 were isolated. [28]…”