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Mantidisflavin A ( 1 ) was isolated from the egg cases of the Tenodera sinensis Saussure. It exhibits an unprecedented 6/6/6/5/5 skeleton, accompanied by the formation of two additional fused heterocycles through a novel C-C bond and an oxygen bridge on riboflavin backbone. The structure of 1 was identified by spectroscopic and computational methods. To assess the inhibitory effect against renal fibrosis, compound 1 was evaluated in TGF-β1-induced rat kidney epithelial cells, and the results were compared to those of its precursor, riboflavin.

Aspongopyrimidine A ( 1 ), a hexa-1,3-diene-histidine-hexanoic acid adduct featuring a 4,5-dihydro-2 H -10λ 4 -imidazo[5,1- f ]pyrrolo[2,1- b ]pyrimidine motif, was isolated from the insect Aspongopus chinensis . The structure was clarified by spectroscopic and computational methods and X-ray diffraction. Peralkylation of N -atoms in histidine by two C6 units makes 1 an inner salt with a 5/6/5 tricyclic system. Biological evaluation found that 1 exerts activity against Alzheimer's disease targeting MAPRE3 through a chemical proteomics approach. This study revealed unusual modifications of amino acids as the fundamental units of protein.

We report on the synthesis of a cage-type calix[4]pyrrole ( 1 ) bearing an additional basic pyridinebisthiazolamine group on the strap. The receptor in its protonated form shows strong affinity and selectivity for sulfate over a wide range of inorganic anions. With receptor 1 as a liquid-liquid extractant, H + /SO 4 2- in the form of H 2 SO 4 is almost quantitatively extracted from an aqueous solution containing HNO 3 at a high concentration to CH 2 Cl 2 in a recyclable manner.

Aspertaichunol A ( 1 ), a polyketide with a novel scaffold, was isolated from the medicinal insect ( Periplaneta americana )-derived endophytic Aspergillus taichungensis SMU01. Its structure was assigned on the basis of spectroscopic data and quantum chemical computational methods. Notably, 1 possesses an uncommon tricyclo[6.2.0.0 2,6 ]decane motif and an unusual bridgehead double bond (anti-Bredt system). A plausible biosynthetic pathway, involving a key intramolecular [2+2] cycloaddition and a reductive cyclization, is postulated. Finally, the immunomodulatory activity of 1 at 20 nM was evaluated by promoting Th9 cell differentiation from naive CD4 + CD62L + T cells.

Populusene A ( 1 ), an unprecedented carbon skeleton featuring a bicyclo[8.4.1]pentadecane nucleus and a bridgehead double bond (anti-Bredt system), and populusin A ( 2 ), a cembrane-type diterpenoid possessing an uncommon dioxatricyclo[6.6.1.1 2,5 ]hexadecane scaffold, were isolated from the exudates of Populus euphratica. Their structures were elucidated by spectroscopic, computational, and crystallographic methods. A plausible biosynthetic route for 1 and 2 was proposed. Compounds 1 and 2 were found to significantly inhibit the production of TNF-α and IL-6 and the expression of iNOS, COX-2, and p-NF-κB at 125 nM in RAW264.7 cells.

Aspongdopamines A and B ( 1 and 2 ), unusual adducts composed of N -acetyldopamine and adenine were isolated from the insect Aspongopus chinensis . Compounds 1 and 2 are positional isomers both isolated as racemates. Chiral separation assisted by 14-step total synthesis and computation including vibrational circular dichroism calculations allowed us to unambiguously assign the absolute configurations of eight stereoisomers. Renal fibrosis inhibition of the stereoisomers was evaluated in TGF-β1-induced rat kidney epithelial cells.

Commiphoranoids A-E ( 1 - 5 ), five novel sesquiterpenoids, dinorditerpenoids, and heterodimers with unprecedented carbon skeletons, were isolated from Resina Commiphora . The structure of 1 was secured by X-ray crystallography. Compound 4 represents the first example of C 38 terpenoids, whereas 5 is a C 30 terpenoid formed by two types of sesquiterpenoids. These metabolites possess lipid regulatory activities via activating PPARα and CPT1.

(±)-Dispirocochlearoids A-C ( 1 - 3 ), meroterpenoids with a 6/6/5/6/6/6 ring system, were isolated from Ganoderma cochlear . 1 - 3 are selective COX-2 inhibitors with an IC 50 value of (-)- 2 at 386 nM. Site-directed mutagenesis identified His351 as a COX-2 active site. In vivo anti-inflammatory activities of (-)- 2 were performed against acute lung injury in mice.

(±)-Lucidumone ( 1 ), an enantiomeric meroterpenoid possessing an unprecedented skeleton comprising a fused 6/5/6/6/5 polycyclic system, was isolated from Ganoderma lucidum and structurally identified. The absolute configuration of (-) -1 was assigned by single-crystal X-ray crystallography. A plausible biosynthetic pathway for 1 is proposed. A chemical biology approach reveals that (-)- 1 selectively inhibits COX-2 by directly binding with an amino acid residue of Tyr385, representing a new structure scaffold of COX-2 inhibitors.

Populusone (1), a cembrane-type macrocyclic trinorditerpenoid, was isolated from the exudates of Populus euphratica and shown to have an unprecedented carbon skeleton, The structure was identified using spectroscopic methods and X-ray crystallography. A possible pathway for the biosynthesis of 1 was proposed. Populusone (10 μM) was found to promote proliferation and differentiation of umbilical cord derived mesenchymal stem cells into keratinocyte like cells.

Belamchinanes A-D (1-4), four triterpenoids with an unprecedented skeleton, were isolated from the seeds of Belamcanda chinensis and fully characterized. The structures of belamchinanes feature a 4/6/6/6/5 polycyclic system in which a four-membered carbocyclic ring bridges the C-1 and C-11 positions of a classical triterpenoid framework. A plausible pathway for the biosynthesis of 1-4 is proposed. Biological studies reveal that 1-4 dose-dependently protect age-related renal fibrosis in vitro .

Two sesquiterpene dimers, commiphoratones A (1) and B (2), were isolated from Resina Commiphora. Their structures were elucidated by spectroscopic, computational, and crystallographic methods. Compounds 1 and 2 represent an unusual pattern of dimerization between two types of sesquiterpenes. Moreover, compound 1 has a saddle shape. The plausible biosynthetic pathway for 1 and 2 is presented. Bioassay showed that 1 and 2 significantly block lipid metabolism in a concentration-dependent manner.

Ganotheaecolin A (1), a novel ergosterol with a rare naphtho[1,8-ef]azulene ring system, was isolated from the fruiting bodies of Ganoderma theaecolum. Its structure was determined by spectroscopic data and computational methods. Compound 1 represents a 6/6/7/5-fused carbon skeletal ergosterol typically formed by Wagner-Meerwein rearrangement, whose plausible biosynthetic pathway was briefly discussed. Finally, the neurotrophic activity of 1 was examined using PC12 cells.

Commiphoranes A-D (1-4), four novel aromatic terpenoids with unprecedented carbon skeletons, were isolated from Resina Commiphora. Their structures were identified by spectroscopic and crystallographic methods. Compounds 1 and 2 are dinorditerpenoids characteristic of a 6/6/6/6 ring system. In contrast, compounds 3 and 4 are sesquiterpenoids possessing a 5/6/7 backbone. Biological evaluation reveals that 3 could significantly attenuate overproduction of fibronectin, collagen I, and α-SMA in TGF-β1-induced rat renal proximal tubular cells.

(+)- and (-)-Sinensilactam A (1), novel hybrid metabolites possessing a unique 2H-pyrrolo[2,1-b][1,3]oxazin-6(7H)-one ring system, were isolated from the fruit bodies of Ganoderma sinensis. The structures of these substances and absolute configurations at their stereocenters were assigned using spectroscopic and computational methods along with X-ray crystallographic analysis. A plausible pathway for the biosynthesis of 1 is proposed. (-)-1 was found to be a Smad3 phosphorylation inhibitor in TGF-β1 induced human renal proximal tubular cells.

Applanatumin A (1), a novel meroterpenoid dimer, was isolated from the fungus Ganoderma applanatum. Its structure and absolute configuration were assigned on the basis of spectroscopic and computational data. Notably, 1 possesses a new hexacyclic skeleton containing a spiro[benzofuran-2,1'-cyclopentane] motif. A plausible pathway, involving a key Diels-Alder reaction, is proposed for the biosynthesis of 1. Applanatumin A exhibits potent antifibrotic activity in TGF-β1-induced human renal proximal tubular cells.

(+)- and (-)-cochlearols A (1) and B (2), two meroterpenoids with novel polycyclic skeletons, were isolated from the fruiting bodies of the fungus Ganoderma cochlear. Their structures and stereochemistry were determined by using spectroscopic, computational and single-crystal X-ray diffraction methods. Cochlearol A is a new normeroterpenoid containing a naturally unusual dioxaspiro[4.5]decane motif. Biological studies showed that (-)-2 is a strong inhibitor of p-Smads, exhibiting renoprotective activities in TGF-β1 induced rat renal proximal tubular cells.

(±)-Aspongamide A (1), an unusual trimer of N-acetyldopamine (NADA) bearing a novel tetrahydrobenzo[a]dibenzo[b,e][1,4]dioxine structure, and a pair of NADA dimeric enantiomers (2) were isolated from Aspongopus chinensis. The structures of compounds 1 and 2 were assigned using spectroscopic methods. Compound 1 was found to be an inhibitor of Smad3 phosphorylation in transforming growth factor-β1 (TGF-β1) induced rat renal proximal tubular cells and suppressed extracellular matrix expression in mesangial cells under diabetic conditions.

(+)-Lingzhiol and (-)-lingzhiol, a pair of rotary door-shaped meroterpenoidal enantiomers, were isolated from Ganoderma lucidum. Their structures were identified by spectroscopic methods and X-ray diffraction crystallography. Lingzhiol bears an unusual 5/5/6/6 ring system characteristic of sharing a C-3'-C-7' axis. Biological evaluation showed that (+)-lingzhiol or (-)-lingzhiol could selectively inhibit the phosphorylation of Smad3 in TGF-β1-induced rat renal proximal tubular cells and activate Nrf2/Keap1 in mesangial cells under diabetic conditions.

Toxicodenanes A-C (1-3), representing sesquiterpenoids with three new carbon skeletons, were isolated from the dried resin of Toxicodendron vernicifluum. Their structures were identified by spectroscopic data and X-ray diffraction crystallography. Their plausible biosynthetic route was proposed via the isolated intermediate (4). Compounds 2 and 3 could significantly inhibit overproduction of fibronectin, collagen IV, and IL-6 in high-glucose-induced mesangial cells in a dose- and time-dependent manner, showing their potential in diabetic nephropathy.