Halichonic acid, a new rearranged bisabolene-type sesquiterpene from a marine sponge Halichondria sp.
Graphical abstract
Introduction
Marine sponges are rich sources of structurally-unique compounds [1], [2], [3]. A variety of nitrogenous bisabolene-type sesquiterpenes have been isolated from several sponges of the class Demospongiae, including Theonella swinhoei [4], Acanthella cavernosa [5], Halichodoria sp. [6], Axinyssa sp. [7], [8], [9], [10], Raphoxya sp. [11], and Ciocalypta sp. [12]. These bisabolene derivatives contain unique nitrogenous functional groups, such as an isothiocyanate, isonitrile, and formamide either at C-3 or C-7 of the bisabolene frameworks. They exhibit a broad range of biological activities including cytotoxicity [6], [8], antimicrobial activity [6], and antifouling activity [13]. The biosynthetic pathways of these nitrogenous sesquiterpenes have attracted much attention, and incorporation experiments indicated that the precursor of the isonitrile group was either inorganic cyanide [14], [15] or amino acids associated with the metabolism of tetrahydrofolate [16]. A biosynthetic enzyme catalyzing the formation of the isonitrile group from glycine was recently identified in several actinobacteria [17].
In our continuing research into new bioactive sponge metabolites, the extract of a sponge Halichondria sp. [18] was found to be cytotoxic. Its purification afforded a new compound 1, containing an unusual 3-azabicyclo[3.3.1]nonene skeleton, together with a known nitrogenous bisabolene derivative 2 [6].
Section snippets
Results and discussion
The EtOH extract of the marine sponge suspended in H2O was extracted with EtOAc, and the organic layer was concentrated and partitioned between n-hexane and 90% MeOH [19]. The 90% MeOH layer (2.8 g) showed cytotoxicity, and the presence of a major compound was suggested by TLC. A portion of the 90% MeOH fraction (0.5 g) was purified by size-exclusion HPLC to afford (6R,7S)-7-amino-7,8-dihydro-α-bisabolene (2) (62.5 mg) as a cytotoxic principle. In order to isolate the alkaloidal congeners in
Conclusion
A new sesquiterpene alkaloid halichonic acid (1) possessing a unique 3-azabicyclo[3.3.1]nonene structure was isolated from a marine sponge Halichondria sp., together with (6R,7S)-7-amino-7,8-dihydro-α-bisabolene (2), which was a cytotoxic principle in this sponge. The structure of 1 including its absolute configuration was determined by spectroscopic and computational methods. It is possible that 1 is biosynthesized from farnesyl pyrophosphate and glycine.
Acknowledgements
This work was financially supported by JSPS KAKENHI Grants 22406001 (S.T.), 17H03994 (S.T.), 18K14933 (Y.H.), and 18K06719 (H.K.) of Japan.
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