Briarane Diterpenoids Isolated from Octocorals between 2014 and 2016

The structures, names, bioactivities, and references of 124 briarane-type natural products, including 66 new metabolites, isolated between 2014 and 2016 are summarized in this review article. All of the briarane diterpenoids mentioned in this review were isolated from octocorals, mainly from Briareum violacea, Dichotella gemmacea, Ellisella dollfusi, Junceella fragilis, Junceella gemmacea, and Pennatula aculeata. Some of these compounds exhibited potential biomedical activities, including anti-inflammatory activity, antibacterial activity, and cytotoxicity towards cancer cells.


Introduction
Following previous review articles from our research group focused on marine-origin briarane-type natural products [1][2][3][4][5], this review covers the literature from 2014 to January 2017, and describes 124 briarane-related diterpenoids (including 66 new metabolites), most of which are characterized by the presence of a γ-lactone moiety fused to a bicyclo [8.4.0] ring system, obtained from various octocorals (Figure 1), mainly Briareum violacea, Briareum spp. Dichotella gemmacea, Ellisella dollfusi, Junceella fragilis, Junceella gemmacea, and Pennatula aculeata. Many of these compounds exhibited interesting bioactivities in vitro, which might indicate a potential for use in biomedical applications. This survey of briarane-related compounds is presented taxonomically according to genus and species.

Briareum violacea (Family Briareidae)
The taxonomic position of octocorals affiliated with the genus Briareum (= Asbestia, Pachyclavularia, and Solenopodium) [6] has been found to be situated near the transition between Alcyonacea and Gorgonacea, in both taxonomic and chemical terms [6][7][8]. In 1977, briarein A, the first briarane-type diterpenoid identified, was isolated from the Caribbean octocoral Briareum asbestinum [9], and since then Briareum has been the main organism from which briarane-type natural products have been obtained.

Briareum violacea (Family Briareidae)
The taxonomic position of octocorals affiliated with the genus Briareum (=Asbestia, Pachyclavularia, and Solenopodium) [6] has been found to be situated near the transition between Alcyonacea and Gorgonacea, in both taxonomic and chemical terms [6][7][8]. In 1977, briarein A, the first briarane-type diterpenoid identified, was isolated from the Caribbean octocoral Briareum asbestinum [9], and since then Briareum has been the main organism from which briarane-type natural products have been obtained.

Briareum violacea (Family Briareidae)
The taxonomic position of octocorals affiliated with the genus Briareum (= Asbestia, Pachyclavularia, and Solenopodium) [6] has been found to be situated near the transition between Alcyonacea and Gorgonacea, in both taxonomic and chemical terms [6][7][8]. In 1977, briarein A, the first briarane-type diterpenoid identified, was isolated from the Caribbean octocoral Briareum asbestinum [9], and since then Briareum has been the main organism from which briarane-type natural products have been obtained.

Pennatula aculeata (Family Pennatulidae)
Investigation of the chemical constituents of P. aculeata, collected from Dinawan Island in Sabah, Malaysia, afforded novel briarane 2-acetoxyverecynarmin C (66) [63] (Figure 10). The structure of the new briarane 66 was elucidated by analysis of spectroscopic data, and this compound showed moderate inhibitory activity towards COX-1 and COX-2, with IC50 values of 44.3 and 47.3 μM, respectively. The 2-acetoxy group in 66 was found to be located on the α-face, relative to Me-15 and H-10, which is a rare occurrence in briarane-related analogues.

Conclusions
Since briarein A, the first briarane-type natural product, was prepared from the Caribbean octocoral Briareum asbestinum in 1977 [9], over 600 briarane-type diterpenoids have been isolated from a wide variety of marine life to date. A large portion of these natural compounds has been prepared from soft corals belonging to the orders Alcyonacea and Gorgonacea. Compounds of this type of diterpenoid have been demonstrated to possess various bioactivities in vitro, such as anti-inflammatory activity, antibacterial activity, and cytotoxicity towards cancer cells. For example, one of the compounds of this type, excavatolide B [13], has been proven to possess extensive biomedical bioactivities, such as anti-inflammatory, analgesic, the attenuation of rheumatoid arthritis activities, anticancer, and the modulation of the electrophysiological characteristics and calcium homeostasis in atrial myocytes [64][65][66][67]. Due to the structural diversity and biomedical bioactivities, there has been little synthetic work on briarane analogues [68,69]. It is interesting to note that all briaranes reported as having been isolated between 2014 and 2016 were all collected from octocorals distributed in the Indo-Pacific Ocean, particularly from the South China Sea.

Pennatula aculeata (Family Pennatulidae)
Investigation of the chemical constituents of P. aculeata, collected from Dinawan Island in Sabah, Malaysia, afforded novel briarane 2-acetoxyverecynarmin C (66) [63] (Figure 10). The structure of the new briarane 66 was elucidated by analysis of spectroscopic data, and this compound showed moderate inhibitory activity towards COX-1 and COX-2, with IC 50 values of 44.3 and 47.3 µM, respectively. The 2-acetoxy group in 66 was found to be located on the α-face, relative to Me-15 and H-10, which is a rare occurrence in briarane-related analogues.

Pennatula aculeata (Family Pennatulidae)
Investigation of the chemical constituents of P. aculeata, collected from Dinawan Island in Sabah, Malaysia, afforded novel briarane 2-acetoxyverecynarmin C (66) [63] (Figure 10). The structure of the new briarane 66 was elucidated by analysis of spectroscopic data, and this compound showed moderate inhibitory activity towards COX-1 and COX-2, with IC50 values of 44.3 and 47.3 μM, respectively. The 2-acetoxy group in 66 was found to be located on the α-face, relative to Me-15 and H-10, which is a rare occurrence in briarane-related analogues.

Conclusions
Since briarein A, the first briarane-type natural product, was prepared from the Caribbean octocoral Briareum asbestinum in 1977 [9], over 600 briarane-type diterpenoids have been isolated from a wide variety of marine life to date. A large portion of these natural compounds has been prepared from soft corals belonging to the orders Alcyonacea and Gorgonacea. Compounds of this type of diterpenoid have been demonstrated to possess various bioactivities in vitro, such as anti-inflammatory activity, antibacterial activity, and cytotoxicity towards cancer cells. For example, one of the compounds of this type, excavatolide B [13], has been proven to possess extensive biomedical bioactivities, such as anti-inflammatory, analgesic, the attenuation of rheumatoid arthritis activities, anticancer, and the modulation of the electrophysiological characteristics and calcium homeostasis in atrial myocytes [64][65][66][67]. Due to the structural diversity and biomedical bioactivities, there has been little synthetic work on briarane analogues [68,69]. It is interesting to note that all briaranes reported as having been isolated between 2014 and 2016 were all collected from octocorals distributed in the Indo-Pacific Ocean, particularly from the South China Sea.

Conclusions
Since briarein A, the first briarane-type natural product, was prepared from the Caribbean octocoral Briareum asbestinum in 1977 [9], over 600 briarane-type diterpenoids have been isolated from a wide variety of marine life to date. A large portion of these natural compounds has been prepared from soft corals belonging to the orders Alcyonacea and Gorgonacea. Compounds of this type of diterpenoid have been demonstrated to possess various bioactivities in vitro, such as anti-inflammatory activity, antibacterial activity, and cytotoxicity towards cancer cells. For example, one of the compounds of this type, excavatolide B [13], has been proven to possess extensive biomedical bioactivities, such as anti-inflammatory, analgesic, the attenuation of rheumatoid arthritis activities, anticancer, and the modulation of the electrophysiological characteristics and calcium homeostasis in atrial myocytes [64][65][66][67]. Due to the structural diversity and biomedical bioactivities, there has been little synthetic work on briarane analogues [68,69]. It is interesting to note that all briaranes reported as having been isolated between 2014 and 2016 were all collected from octocorals distributed in the Indo-Pacific Ocean, particularly from the South China Sea.