Natural Product Chemistry of Gorgonian Corals of the Family Plexauridae Distributed in the Indo-Pacific Ocean

The structures, names, bioactivities and references of 105 natural products obtained from gorgonian corals belonging to the family Plexauridae with an Indo-Pacific distribution are described in this review. All compounds mentioned in this review were obtained from gorgonian corals belonging to the genera Astrogorgia, Bebryce, Echinomuricea, Euplexaura and Menella.


Introduction
Over the past thirty-four years, 105 natural products have been reported from gorgonian corals belonging to the genera Astrogorgia, Bebryce, Echinomuricea, Euplexaura and Menella with an Indo-Pacific distribution, all belonging to the family Plexauridae (Cnidaria: Anthozoa: Gorgonacea) [1]. This review summarizes the structures, names, bioactivities and references of all compounds in tabular form.

Structure
No. Name Biological Activity Ref.   In biological activity experiments, sesquiterpenoid 29 displayed a significant inhibitory effect on the release of elastase by human neutrophils. This compound also exhibited weak cytotoxicity toward DLD-1 and CCRF-CEM tumor cells [9]. Steroid 31 displayed significant inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils [11]. Clerodane 32 exhibited weak cytotoxicity toward MOLT-4 and HL-60 tumor cells and displayed a significant inhibitory effect on the generation of superoxide anions by human neutrophils [12]. Halimane 33 exhibited cytotoxicity toward K562, MOLT-4, HL-60, DLD-1 and LoVo tumor cells and displayed a significant inhibitory effect on the release of elastase by human neutrophils [13].

Euplexaura anastomosans
Four new steroids of the cholestane class, anastomosacetals A-D (34-37), were obtained from the gorgonian coral E. anastomosans, collected off the shore of Keomun Island, South Sea Korea [14] ( Table 7). The structures of steroids 34-37 were determined by spectroscopic methods, and these four compounds are the first examples of marine steroids possessing an unusual hemiacetal linkage formed by oxidation of the C-21 methyl group.
In addition, seven new moritoside class farnesylhydroquinone glycosides, euplexides A-G (38-44), were isolated from E. anastomosans [15,16] (Table 7). The structures of glycosides 38-44, including their absolute stereochemistry, were elucidated by spectroscopic and chemical methods. Compounds 38-44 exhibited moderate cytotoxicity and antioxidant activity as well as an inhibitory effect against PLA 2 .  Table 8). The structure of guaiazulene (46) from E. erecta was determined by spectroscopic methods and by comparison of the spectral data with those of reported data. This is the first isolation of guaiazulene from an animal, and this compound showed mild antimicrobial activity [18]. [17]

Euplexaura flava
Four new unnamed fatty acid derivatives 47-50, which contain a butenolide moiety, were isolated from the gorgonian coral E. flava, collected at the coral reef of Ishigaki Island, Okinawa, Japan. The structures of butenolides 47-50 were elucidated by spectroscopic and chemical methods [19] (Table 9).

Euplexaura nuttingi
Six new tetraprenylated purine alkaloids, nuttingins A-F (51-56), were isolated together with five new compounds, malonganenones D-H (57-61), and three known metabolites, malonganenones A-C (62-64), from the gorgonian coral E. nuttingi collected in Uvinage, Pemba Island, Tanzania. The structures of compounds 51-64 were elucidated by interpretation of spectral data [20] (Table 10). A and B (51 and 52), C-E (53-55), malonganenones D and E (57 and 58), and F and G (59 and 60) have been found to inhibit growth of K562 and UT7 tumor cells. Nuttingins A-E (51-55) and malonganenones D-H (57-61) induce apoptosis in transformed mammalian cells [20].      Moritoside (65), a new hydroquinone glycoside derivative was isolated from the gorgonian Euplexaura sp., collected near Morito beach in the Gulf of Sagami, Japan. The structure of glycoside 65 was determined by spectroscopic and chemical methods [21] (Table 11). This is the first example of the occurrence of D-altrose in natural products, and this compound inhibits the first cell division of fertilized starfish (Asterina pectinifera) eggs.
(-)-Hydroxy-lindestrenolide (98) and (+)-chloranthalactone B (104) were proven to be enantiomers of the known sesquiterpenoids (+)-hydroxylindestrenolide and chloranthalactone B, respectively [30,31]. Menelloide A (99) was found to possess a new carbon skeleton [31]. Seco-germacrane anhydride (105) was a known metabolite and there have been no reports of seco-germacrane anhydride (105) being obtained from any marine organism previously [34]. Several of these compounds displayed inhibitory effects on the generation of superoxide anions and the release of elastase by human neutrophils.

Conclusions
The search for bioactive natural products from marine organisms has been remarkably successful, and octocorals have been proven to be rich sources of natural products with potential biomedical application [35][36][37]. In particular, the data reported in this review indicate that terpenoid and steroid derivatives represent the major chemical classes occurring in Indo-Pacific octocoral species belonging to the family Plexauridae. Among the 105 isolated metabolites, in fact, 49 compounds are terpenoid analogs (46.7%) and 45 compounds are steroid metabolites (42.9%). These compounds continue to attract attention owing to their structural novelty, complexity and interesting bioactivities.