Uncommon Diterpenoids from the South China Sea Soft Coral Sinularia humilis and Their Stereochemistry

Abstract

The chemical investigation of the South China Sea soft coral Sinularia humilis has resulted in the isolation of a library of diverse diterpenoids, including four new cembranoids, namely, humilisins A−D (1−4), two new uncommon diterpenoids possessing a tetradecahydrocyclopenta[3′,4′]cyclobuta[1′,2′:4,5]cyclonona[1,2-b]oxirene ring system, namely, humilisins E and F (5 and 6), and eight known related compounds (7−14). Humilisin A (1) is the first cembranoid with an ether linkage between C-3 and C-7. The structures and absolute configurations of 1−8 were determined by extensive spectroscopic data analyses, chemical reactions, and a series of quantum chemical calculations including quantum mechanical−nuclear magnetic resonance (QM-NMR), time-dependent density functional theory−electronic circular dichroism (TDDFT-ECD), and optical rotatory dispersion (ORD) methods. In bioassay, compound 6 displayed anti-inflammatory activity in lipopolysaccharide (LPS)-stimulated BV-2 microglia cells.

Chemical Diversity and Biological Activity of Secondary Metabolites from Soft Coral Genus Sinularia since 2013

“…Four new cembranoids, humilisins A−D (134−137), and two new uncommon diterpenoids humilisins E and F (138 and 139) with new carbon skeletons were isolated from the South China Sea soft coral S. humilis [4]. Humilisin A (134) was the first cembranoid with an ether linkage between C-3 and C-7.…”

“…Humilisin A (134) was the first cembranoid with an ether linkage between C-3 and C-7. Humilisins E and F (138 and 139) possessed a tetradecahydrocyclopenta [3 ,4 ]cyclobuta[1 ,2 :4,5]cyclonona [1,2-b]-oxirene ring system [4]. Compound 139 displayed a significant inhibitory effect on LPS-induced inflammatory response (NO production) in BV-2 microglial cells, and the level of NO decreased [4].…”

“…As reported, Sinularia is well-known to produce a wealth of diverse and com plex secondary metabolites, such as sesquiterpenes (10%), diterpenes (46%), norsesqui erpenes (2%), norditerpenes (9%), steroids/steroidal glycosides (22%), and other type (11%) (Figure 1) [1][2][3]. These metabolites exhibit a wide range of biological activities, suc as cytotoxic, anti-inflammatory, antifouling, and anti-microbials [4][5][6][7][8][9][10][11][12][13][14]. There are some published literature reviews on the genus Sinularia.…”

Cembranoids of Soft Corals: Recent Updates and Their Biological Activities

“…Lastly, six novel compounds were reported from Sinularia humilis collected from Ximao Islands, Hainan, China namely humilisins A-F 217–222 . Compound 222 was the only reported diterpenoid that possessed biological activity by decreasing NO level in anti-inflammatory assay [ 62 ].

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“…Furthermore, those compounds also inhibited the release of elastase to 35.1 ± 10.6; 48.2 ± 12.5; 35.6 ± 10.7; 27.6 ± 12.8; 29.7 ± 11.1; 16.7 ± 10.2; and 27.6 ± 12.0%, respectively, at concentration of 30 µM [ 48 ]. Lastly, diterpenoid 222 isolated from Sinularia humilis collected in Ximao Islands have significant anti-inflammatory effects in LPS-stimulated BV-2 microglial cells with 83.96% ± 2.02% and 65.70% ± 2.76% NO level decrease at 10 and 20 μM, respectively [ 62 ].…”