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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. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A detailed chemical investigation of the South China Sea nudibranch Hexabranchus sanguineus, as well as its possible sponge‐prey Acanthella cavernosa, led to the isolation of fifteen new nitrogenous sesquiterpenoids, namely ximaocavernosins A−O, including seven cadinanes (1—7), seven spiroaxanes (12—18) and one aromadendrane (19), together with thirteen known related compounds (8—11 and 20—28). Compounds (±)‐1—9 (except for 4 and 6) were further separated by chiral‐phase HPLC to their corresponding unequal enantiomers, respectively. Their structures and absolute configurations were determined by a combination of extensive spectroscopic data analysis, quantum mechanical nuclear magnetic resonance (QM‐NMR) methods, Mosher's method, X‐ray diffraction analysis and/or time‐dependent density functional theory/electronic circular dichroism (TDDFT‐ECD) calculation. The commonly existed nitrogenous sesquiterpenoids in these two animals are suggested to be chemical markers for their prey‐predator relationship. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Two new bis‐quinolizidine alkaloids, neopetrosiasins A (1) and B (2), possessing cis‐ and trans‐quinolizidine nuclei, one known related analogue petrosin (3) and three known xestospongins (4—6), were isolated from the South China Sea sponge Neopetrosia chaliniformis. The structures of new compounds were unambiguously determined by extensive spectroscopic and single‐crystal X‐ray analyses. In bioassay, compounds 4—6 exhibited moderate cytotoxicity against several human cancer cells. [ABSTRACT FROM AUTHOR]

Main observation and conclusion: Four new cembranoids, 6‐oxo‐cembrene‐A (1), lobocrassins G—H (2—3), and 14‐epi‐lobophytolide B (4), along with eight known related compounds (5—12), were isolated from the South China Sea soft coral Lobophytum crassum. Their structures were established by extensive spectroscopic analysis and by comparison of the spectral data with those reported in the literatures. The absolute stereochemistry of 14‐epi‐lobophytolide B (4) was established by time‐dependent density functional theory electronic circular dichroism (TDDFT‐ECD) calculations, whereas that of three known metabolites (6, 11 and 12) was also determined, for the first time, by using modified Mosher's method and/or X‐ray diffraction analyses. In bioassay, the cembranoids 6, 7 and 12 showed significant anti‐tumoral activity against A549, HT‐29, SNU‐398 and Capan‐1 tumor cell lines with IC50 values ranging from 1.5 to 7.4 μmol/L. A preliminary structure‐activity relationship was also discussed. [ABSTRACT FROM AUTHOR]

Placobranchus ocellatus is well known to produce diverse and complex γ‐pyrone polypropionates. In this study, the chemical investigation of P. ocellatus from the South China Sea led to the discovery and identification of ocellatusones A–D, a series of racemic non‐γ‐pyrone polyketides with novel skeletons, characterized by a bicyclo[3.2.1]octane (1, 2), a bicyclo[3.3.1]nonane (3) or a mesitylene‐substituted dimethylfuran‐3(2H)‐one core (4). Extensive spectroscopic analysis, quantum chemical computation, chemical synthesis, and/or X‐ray diffraction analysis were used to determine the structure and absolute configuration of the new compounds, including each enantiomer of racemic compounds 1–4 after chiral HPLC resolution. An array of new and diversity‐generating rearrangements is proposed to explain the biosynthesis of these unusual compounds based on careful structural analysis and comparison with six known co‐occurring γ‐pyrones (5–10). Furthermore, the successful biomimetic semisynthesis of ocellatusone A (1) confirmed the proposed rearrangement through an unprecedented acid induced cascade reaction. [ABSTRACT FROM AUTHOR]

Benzoxepane derivatives were designed and synthesized, and one hit compound emerged as being effective in vitro with low toxicity. In vivo, this hit compound ameliorated both sickness behavior through anti‐inflammation in LPS‐induced neuroinflammatory mice model and cerebral ischemic injury through anti‐neuroinflammation in rats subjected to transient middle cerebral artery occlusion. Target fishing for the hit compound using photoaffinity probes led to identification of PKM2 as the target protein responsible for anti‐inflammatory effect of the hit compound. Furthermore, the hit exhibited an anti‐neuroinflammatory effect in vitro and in vivo by inhibiting PKM2‐mediated glycolysis and NLRP3 activation, indicating PKM2 as a novel target for neuroinflammation and its related brain disorders. This hit compound has a better safety profile compared to shikonin, a reported PKM2 inhibitor, identifying it as a lead compound in targeting PKM2 for the treatment of inflammation‐related diseases. [ABSTRACT FROM AUTHOR]

Two new highly oxidized formamidobisabolene sesquiterpenes ( 1 and 2), together with seven known related analogues ( 3 - 9), were isolated from a Hainan sponge Axinyssa variabilis. Their structures were determined by extensive 1D- and 2D- NMR and MS spectra analyses, and by comparison of their spectroscopic data with those of the related model compounds. The plausible biosynthetic relationship between compounds 1 - 9 has also been described. [ABSTRACT FROM AUTHOR]

A bio-inspired strategy was used to complete the formal synthesis of the antitubercular hirsutellone B and congeners A and C, through construction of its decahydrofluorene core from a linear polyene strand activated at both ends by a silyl enol ether and an allyl acetate. Our synthesis features a key electrophilic cyclization, starting with the remote activation (by [Yb(OTf)3] or BF3 ⋅OEt2) of the allyl acetate and stereoselectively affording the C ring. This was followed by an intramolecular Diels-Alder reaction to get the tricyclic core of the natural product. The stereoselective reduction of the resulting ketone towards the formal intermediate was critical to the success of this strategy. [ABSTRACT FROM AUTHOR]

Review: 238 refs. [ABSTRACT FROM AUTHOR]

A bio-inspired strategy is used to complete the formal synthesis of the antitubercular hirsutellone B (I) and congeners A (II) and C (III), through construction of its decahydrofluorene core from a linear polyene strand activated at both ends by a silyl enol ether and an allyl acetate (not shown). [ABSTRACT FROM AUTHOR]

Review: 115 refs. [ABSTRACT FROM AUTHOR]