Polyoxygenated cembrane-type diterpenes from the Hainan soft coral Lobophytum crassum as a promising source of anticancer agents with ErbB3 and ROR1 inhibitory potential.

A detailed chemical investigation of the Hainan soft coral Lobophytum crassum led to the identification of a class of polyoxygenated cembrane-type macrocyclic diterpenes (1-28), including three new flexible cembranoids, lobophycrasins E-G (2-4), and twenty-five known analogues. Their structures were elucidated by combining extensive spectroscopic data analysis, quantum mechanical-nuclear magnetic resonance (QM-NMR) methods, the modified Mosher's method, X-ray diffraction analysis, and comparison with data reported in the literature. Bioassays revealed that sixteen cembranoids inhibited the proliferation of H1975, MDA-MB231, A549, and H1299 cells. Among them, Compounds 10, 17, and 20 exhibited significant antiproliferative activities with IC50 values of 1.92-8.82 µM, which are very similar to that of the positive control doxorubicin. Molecular mechanistic studies showed that the antitumour activity of Compound 10 was closely related to regulation of the ROR1 and ErbB3 signalling pathways. This study may provide insight into the discovery and utilization of marine macrocyclic cembranoids as lead compounds for anticancer drugs.

Structurally Diverse Diterpenoids from the Sanya Bay Nudibranch Hexabranchus sanguineus and Its Sponge-Prey Chelonaplysilla sp.

Investigation of the South China Sea nudibranch Hexabranchus sanguineus from Sanya Bay afforded, in addition to three known compounds, nine new diterpenoids of the 5,19-cycloclerodane- (sanyanolides A-D), clerodane- (sanyanolide E) and subersin- (sanyanolides F-I) type. Remarkably, six diterpenoids aforementioned from H. sanguineus were also isolated from the sponge Chelonaplysilla sp. from the same water region, suggesting a trophic relationship between H. sanguineus and Chelonaplysilla sp. The structure and absolute configuration of new compounds were established by a combination of spectroscopic data, X-ray diffraction analysis and/or time-dependent density functional theory/electronic circular dichroism calculations. A plausible biogenetic relationship between these diterpenoids, along with the chemo-ecological implications of their co-occurrence in the two organisms investigated, was proposed and discussed. In in vitro bioassays, echinoclerodane A exhibited a potent inhibitory effect (IC50 =2.81 µM) on LPS-induced inflammatory response in RAW 264.7 macrophage cells. In addition, echinoclerodane A and oculatolide showed considerable antibacterial activities with MIC values ranging from 1.0 to 8.0 µg/mL.

Chemistry, Chemo-Ecology, and Biological Activities of Uncommon and Structurally Diverse Sesquiterpenoids from the Sanya Bay Nudibranch Hexabranchus sanguineus.

A detailed chemical investigation of the Sanya Bay nudibranch Hexabranchus sanguineus yielded thirteen new sesquiterpenoids, namely sanyagunins A-H, sanyalides A-C, and sanyalactams A and B, along with eleven known related ones. Sanyalactams A and B feature an unprecedented hexahydrospiro[indene-2,3'-pyrrolidine] core. The structures of new compounds were established by a combination of extensive spectroscopic data analysis, quantum mechanical-nuclear magnetic resonance methods, the modified Mosher's method, and X-ray diffraction analysis. Based on analysis of NOESY correlations and the modified Mosher's method, the stereochemistry of two known furodysinane-type sesquiterpenoids were revised. A plausible biogenetic relationship between these sesquiterpenoids wasproposed and discussed, and a chemo-ecological relationship of the title animal and its possible sponge preys has been analyzed. In bioassays, sanyagunin B showed moderate antibacterial activity, whereas 4α-formamidogorgon-11-ene exhibited potent cytotoxicity with IC50 values ranging from 0.87 to 1.95 µM.

Two New Cembranoids from the Chinese Soft Coral Sarcophyton boettgeri.

Two new cembranoids, namely sarcoboettgerols D and E, together with four known related ones, have been isolated from the soft coral Sarcophyton boettgeri collected from Weizhou Island in the South China Sea. Their structures including absolute configurations were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance methods, time-dependent density functional theory-electronic circular dichroism calculations, as well as comparison with the reported data in the literature. A plausible biogenetic relationship of four cembranoids was proposed. In bioassays, sarcomililatin B exhibited cytotoxic activity against H1299 cell (IC50 =35.0 µM), whereas sarcomililatin B and sarcomililatin A displayed moderate antibacterial activities (MIC 17.4-34.8 µg/mL).

Pitfalls in the structural elucidation of small molecules. A critical analysis of a decade of structural misassignments of marine natural products.

Covering: July 2010 to August 2021This article summarizes more than 200 cases of misassigned marine natural products reported between July 2010 and August 2021, sorting out errors according to the structural elements. Based on a comparative analysis of the original and the revised structures, major pitfalls still plaguing the structural elucidation of small molecules were identified, emphasizing the role of total synthesis, crystallography, as well as chemical- and biosynthetic logic to complement spectroscopic data. Distinct "trends" in natural product misassignment are evident between compounds of marine and plant origin, with an overall much lower incidence of "impossible" structures within misassigned marine natural products.

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa.

One new aromadendrane-type sesquiterpenoid, namely ximaocavernosin P [(+)-1], and three new cadinane-type sesquiterpenoids, namely (+)-maninsigin D [(+)-4], (+)- and (-)-ximaocavernosin Q [(+)- and (-)-5], together with five related known ones [2, 3, (-)-4, 6, and 7], were isolated from the Hainan sponge Acanthella cavernosa. Compounds 4 and 5 were isolated as racemic forms, which were further separated to the corresponding enantiomers [(+)-4/(-)-4 and (+)-5/(-)-5], respectively, by using chiral-phase HPLC. The structures of new compounds were elucidated by extensive spectroscopic analysis and comparison with the reported data. In addition, the absolute configuration of optically pure (+)-1 and 2 were determined by time-dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations or X-ray diffraction analysis. A plausible biosynthetic pathway of these sesquiterpenoids and their internal correlation were proposed and discussed. In an in vitro bioassay, (+)-aristolone (3) exhibited promising anti-inflammatory activity by the inhibition of LPS-induced TNF-α and CCL2 release in RAW 264.7 macrophages.

Ximaoglaucumins A - F, new cembranoids with anti-inflammatory activities from the South China Sea soft coral Sarcophyton glaucum.

Six new cembrane-type diterpenoids, namely ximaoglaucumins A-F (1-6), along with fifteen known related ones (7-10 and 14-24), have been isolated from the soft coral Sarcophyton glaucum collected off the Ximao Island in the South China Sea. Their structures, including absolute stereochemistry, were elucidated by extensive spectroscopic analysis, quantum mechanical nuclear magnetic resonance (QM-NMR) methods, X-ray diffraction analysis, chemical methods, as well as comparison with the reported data in the literature. Further, detailed analysis of spectroscopic data of 7 not only clarified the confusions regarding 7, 11 (sarcophytolol) and 12/13 (sarcotrocheliol) in the literature, but also led to revise the structure of 11, which was mis-assigned due to careless/erroneous interpretation of the 2D NMR spectra, and to correct the structures of 12/13, which were both wrongly depicted. In in vitro bioassay, compounds 8 and 20 exhibited potent inhibitory effects on lipopolysaccharide (LPS)-induced inflammatory responses in BV-2 microglial cells.

Genus Periploca (Apocynaceae): A Review of Its Classification, Phytochemistry, Biological Activities and Toxicology.

The genus Periploca belongs to the family Apocynaceae, which is composed of approximately ten species of plants according to incomplete statistics. Most of these plants serve as folk medicines with a long history, especially Periploca sepium and Periploca forrestii. The botanical classifications, chemical constituents, biological activities and toxicities of the genus Periploca were summarized in the literature from 1897 to early 2019. Though the botanical classification of this genus is controversial, these species are well-known to be rich sources of diverse and complex natural products-above all, cardiac steroids and C21 pregnane steroids with special structures and obvious pharmacological activities. The various crude extracts and 314 isolated metabolites from this genus have attracted much attention in intensive biological studies, indicating that they are equipped with cardiotonic, anti-inflammatory, immunosuppressive, antitumor, antimicrobial, antioxidant, insecticidal and other properties. It is noteworthy that some cardiac glycosides showed hepatotoxicity and cardiotoxicity at certain doses. Therefore, in view of the medical and agricultural value of the genus Periploca, in-depth investigations of the pharmacology in vivo, the mechanisms of biological actions, and the pharmacokinetics of the active ingredients should be carried out in the future. Moreover, in order to ensure the safety of clinical medication, the potential toxicities of cardiac glycosides or other compounds should also be paid attention. This systematic review provides an important reference base for applied research on pharmaceuticals and pesticides from this genus.

[Chemical constituents contained in aerial parts of Emilia sonchifolia].

OBJECTIVE: To study the chemical constituents contained in ethanol extracts from aerial parts of Emilia sonchifolia. METHOD: The compounds were separated and purified with various chromatographic techniques, and their structures were identified on the basis of physicochemical properties and spectral data. RESULT: Fifteen compounds were separated from ethyl acetate fraction of 90% ethanolic extract and identified as rhamnetin (1), isorhamnetin (2), quercetin (3), luteolin (4), tricin-7-O-beta-D-glucopyranoside (5), 8-(2"-pyrrolidinone-5"-yl) -quercetin (6), 5, -2', 6'-trihydroxy-7, 8-dimethoxyflavone-2'-O-beta-D-glucopyranoside (7), succinic acid (8), fumaric acid (9), p-hydroxybenzoic acid (10), 4-hydroxy isophthalic acid (11), 3, 4-dihydroxycinnamic acid (12), esculetin (13), isowedelolactone (14) and uracil (15), respectively. CONCLUSION: All compounds except compound 3 were separated from this genus for the first time.

Stereochemical insights into neuroprotective alkaloids from the aerial parts of Emilia sonchifolia.

A new alkaloid featured with a dibenz[c,e]azepin-5-one scaffold, namely emililactam A (3), together with a known pyrrolidine alkaloid (emilisonchine, 1) and a known flavonoid alkaloid [8-(2″-pyrrolidinone-5″-yl)-quercetin, 2] were isolated from the aerial parts of Emilia sonchifolia. Compounds 1 and 2 were isolated as racemic forms which were further separated, for the first time, to their corresponding enantiomers [(+)-1/(-)-1 and (+)-2/(-)-2], respectively, by using chiral-phase HPLC. The structure of new compound 3 was elucidated by extensive spectroscopic analysis. In addition, the absolute configurations of optically pure (+)-1/(-)-1 and (+)-2/(-)-2 were determined by the time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations. In an in vitro bioassay, compounds (+)-1, (-)-1, (±)-1, and 3 exhibited moderate neuroprotective effects against corticosterone-induced injuries of PC12 cells.

Chemical and biological studies of Daphniphyllum oldhamii from Hunan Province, China.

The fruits, twigs and leaves of Daphniphyllum oldhamii (Hemsl.) K. Rosenthal, collected from Longshan County, Hunan Province, China, were chemically investigated. Three undescribed daphniphyllum alkaloids, namely longshanoldhamines A‒C, and six known related ones have been isolated from the fruits, whereas two undescribed triterpenoids and one undescribed lignan, along with six known triterpenoids, were found in the twigs and leaves. Their structures were elucidated by extensive spectroscopic analysis, X-ray diffraction analysis and comparison with the reported data.

A new cyclohexylacetic acid derivative from the aerial parts of Emilia sonchifolia.

A new cyclohexylacetic acid derivative, named 2-{4-hydroxy-7-oxabicyclo [2.2.1] heptanyl}-acetic acid (1), was isolated from Emilia sonchifolia, together with a known analogue, 2-(1,4-dihydroxy cyclohexanyl)-acetic acid (2). Their structures were determined on the basis of spectroscopic techniques including IR, NMR, HR-ESI-MS and X-ray diffraction.