Natural Product Chemistry of Gorgonian Corals of Genus Junceella–Part III

The structures, names, bioactivities, and references of 82 natural products, including 48 new metabolites, purified from the gorgonian corals belonging to the genus Junceella are described in this review. All compounds mentioned in this review were obtained from Junceella fragilis, Junceella gemmacea, Junceella juncea, and Junceella sp., collected from tropical Indo-Pacific Ocean. Some of these compounds exhibited potential biomedical activities.


Introduction
Following previous review articles focused on marine-origin natural products, this review covers the literature from October 2011 to August 2018, and describes 82 natural products (including 48 new metabolites) from gorgonian corals belonging to the genus Junceella (family Ellisellidae) [1][2][3][4]. Extending from previous reviews in 2004 and 2011 [5,6], this review provides structures, names, bioactivities, and references for all compounds including briarane-and norcembrane-type diterpenoids, sterol, and nucleosides. Many of these compounds exhibited interesting bioactivities in vitro, which might indicate a potential for use in biomedical applications. This survey of natural products from Junceella is presented taxonomically according to species.
Moreover, the norcembranoids 28 and 47-49 were assayed for their potential inhibitory effects against nitric oxide (NO) production induced by lipopolysaccharides (LPS) (large molecules consisting of lipids and polysaccharide composed of O-antigen joined by chemical bonds), in RAW264.7 cells, and these four compounds exhibited the inhibitory activities with 27.8%, 43.5%, 56.0%, and 57.9% inhibition, respectively, at a dose of 100 µM [27]. In order to explore the mechanism of these NO inhibitors, the expression of the antioxidant response element (ARE) mediated lufiferase and NF-κB was evaluated. Norcembranoids 48 and 49 showed the effects against NF-κB by the inhibitory rates of 25.1% and 28.6% in a dose of 50 µM, respectively. Significant induction of luciferase was observed as the dose of 50 µM for 48 and 49 with 3.8 and 5.6 folds more than that of blank control [27]. The antioxidant capacity of 28 and 47-49 were evaluated by the modified 2,2azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation decolorization assay [27]. including calculated electronic circular dichroism (ECD) data. The structures, including the absolute configurations of briaranes 37 and 46, were further established by single-crystal X-ray diffraction analysis using Flack parameter in this study [27]. Compound 28 featured an unprecedented 4,13-and 7,11-fused tetracyclic norcembranoid [27].    [27].
The structures of briaranes 50-54 were elucidated by spectroscopic methods in association with chemical conversion. The absolute configurations of briaranes 50 and 55 were further determined by acetylation of these two compounds to yield the same crystal product and analyses of X-ray crystal data of this compound by Flack parameter further confirmed the absolute configurations of briaranes 50 and 55 [30], although briaranes 56 and 57 existed in an inseparable mixture in CHCl 3 at room temperature. Lowering the temperature to 4 • C resulted in the generation of a crystal, while the Mar. Drugs 2018, 16, 339 5 of 10 X-ray diffraction analysis using Flack parameter determined the crystal product to be in accordance with briarane 56. Each pair of the isomers (50/55, 51/52, 53/54, and 56/57) featured by dynamical interconversion through as acetyl migration in 1,2-diol, which was postulated to be generated under the formation of cyclic orthoacetate intermediated. In the mixture of briaranes 56 and 57, increasing temperature gradients resulted in the variation of 56/57 ratio, while the ratio of 56/57 varied from 1:1 to 2:3 at 50 • C [30]. The mixtures of 50/55, 51/52, 53/54, and 56/57 were tested for their inhibitory effects against NO production induced by LPS in RAW264.7 cells and these four components displayed inhibitory activities against NO production with the inhibition rates of 39   Two new briaranes, fragilides K (58) and L (59), along with five known chlorinated briaranes, gemmacolides V (60) and X (61) [31], praelolide (62) [7,14,16,[32][33][34][35][36][37], and juncins P (63) [35] and ZI (64) [11], were obtained from a Formosan J. fragilis [38] (Figure 5). Based on spectroscopic methods, the structures of briaranes 58 and 59 were elucidated and the cyclohexane rings in 58 and 59 were found to exist in chair and twist boat conformation, respectively. At a concentration of 10 μM, briaranes 59, 61, and 64 showed anti-inflammatory activity against the expression of pro-inflammatory protein inducible nitric oxide synthase (iNOS) to 49.13%, 36.22%, and 43.33%, respectively, and briaranes 60 and 61 elicited reduction of the pro-inflammatory protein cyclooxygenase-2 (COX-2) to 47.49% and 43.64%, respectively [38].

Conclusions
The natural products obtained from gorgonian corals belonging to the genus Junceella complied in this review indicated that the terpenoid derivatives, particularly briarane-type diterpenoids, are the major components of the natural products isolated. Of the 82 metabolites, 75 compounds (91.5%) are briarane-type diterpenoids. Of the briaranes, 50 compounds are halogenated (50/75 = 66.7%). Briarane-type natural products are a large family of natural products that are only isolated from marine organisms and the compounds of this type were suggested originally synthesized from the 3,8-cyclization of cembranoids by the host corals and not by their zooxanthellae [37,53,54]. Briaranetype diterpenoids continue to attract attention owing to their complex structures and potential biomedical activities.
Studies on the novel substances for biomedical use from the marine invertebrates originally distributed in the Indo-Pacific Ocean will play an important role in natural product research [55]. Marine natural products currently under clinical trials are limited. Based on the potential medical use and complex structures, it is very difficult to obtain enough material for further studies by chemical methods. How to make the best use of aquaculture technology to enhance in captivity mass

Conclusions
The natural products obtained from gorgonian corals belonging to the genus Junceella complied in this review indicated that the terpenoid derivatives, particularly briarane-type diterpenoids, are the major components of the natural products isolated. Of the 82 metabolites, 75 compounds (91.5%) are briarane-type diterpenoids. Of the briaranes, 50 compounds are halogenated (50/75 = 66.7%). Briarane-type natural products are a large family of natural products that are only isolated from marine organisms and the compounds of this type were suggested originally synthesized from the 3,8-cyclization of cembranoids by the host corals and not by their zooxanthellae [37,53,54]. Briaranetype diterpenoids continue to attract attention owing to their complex structures and potential biomedical activities.
Studies on the novel substances for biomedical use from the marine invertebrates originally distributed in the Indo-Pacific Ocean will play an important role in natural product research [55]. Marine natural products currently under clinical trials are limited. Based on the potential medical use and complex structures, it is very difficult to obtain enough material for further studies by chemical methods. How to make the best use of aquaculture technology to enhance in captivity mass In the cytotoxic activity test, briaranes 71 and sterol 80 exhibited weak cytotoxicity toward the THP-1 (human acute monocytic leukemia) tumor cells with IC 50 values 55.4 and 130 µM, respectively. Sterol 80 also possessed weak clonogenic activity with INCC 50 53.3 µM toward THP-1. Moreover, sterol 80 produced an inhibition zone 12 mm in diameter against Bacillus subtilis. Briarane 62 inhibited weakly Candida albicans. Briaranes 21 and 71 and sterol 80 inhibited weakly Vibrio parahaemolyticus [49].

Conclusions
The natural products obtained from gorgonian corals belonging to the genus Junceella complied in this review indicated that the terpenoid derivatives, particularly briarane-type diterpenoids, are the major components of the natural products isolated. Of the 82 metabolites, 75 compounds (91.5%) are briarane-type diterpenoids. Of the briaranes, 50 compounds are halogenated (50/75 = 66.7%). Briarane-type natural products are a large family of natural products that are only isolated from marine organisms and the compounds of this type were suggested originally synthesized from the 3,8-cyclization of cembranoids by the host corals and not by their zooxanthellae [37,53,54]. Briarane-type diterpenoids continue to attract attention owing to their complex structures and potential biomedical activities.
Studies on the novel substances for biomedical use from the marine invertebrates originally distributed in the Indo-Pacific Ocean will play an important role in natural product research [55]. Marine natural products currently under clinical trials are limited. Based on the potential medical use and complex structures, it is very difficult to obtain enough material for further studies by