Dongyan Li

Bioactive Acylphloroglucinols with Adamantyl Skeleton from Hypericum sampsonii

Hyperisampsins A-D (1-4), with tetracyclo[6.3.1.1(3,10).0(3,7)]tridecane skeletons and seven biogenetically related congeners (5-11), were isolated from Hypericum sampsonii. Their structures were elucidated by comprehensive spectroscopic techniques. The absolute configuration of 1 was established by ECD calculations, and those of 5 and 9 were confirmed by single X-ray crystallographic analyses. Hyperisampsins A and D showed potent anti-HIV activities with EC50 of 2.97 and 0.97 μM and selectivity index of 4.80 and 7.70, respectively.

Hyperattenins A–I, bioactive polyprenylated acylphloroglucinols from Hypericum attenuatum Choisy

Nine new polyprenylated acylphloroglucinols (PPAPs), hyperattenins A-I (1-9), together with thirteen known analogues (10-22), were isolated from the aerial parts of Hypericum attenuatum Choisy. The structures of 1-9 were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was determined by a single X-ray crystallographic analysis, and the absolute configurations of 2-9 were determined by comparison of experimental and calculated electronic circular dichroism (ECD) spectra. Compound 1 was characterised as a bicyclo[3.3.1] nonane derivative containing an unusual hemiacetal functionality formed by a series of redox reactions on its side chains, which occurs rarely in nature. All new isolates were evaluated for cytotoxic activities against several human cancer cell lines. Compound 9 exhibited significant inhibitory activity against the HL-60 and A-549 cell lines, with IC50 values of 2.04 and 3.26 mu M, respectively. Compound 9 also showed low toxicity to Beas-2B cells (IC50 = 14.36 mu M), suggesting that it could be a selective anti-tumour agent for leukaemia and lung cancer. Compounds 2-8 were also screened for their anti-HIV-1 activities.

Sampbenzophenones A–G, prenylated benzoylphloroglucinol derivatives from Hypericum sampsonii

Seven prenylated benzoylphloroglucinol derivatives, named sampbenzophenones A–G (1–7), together with two known analogues (8 and 9), were isolated from the aerial parts of Hypericum sampsonii. Their structures were elucidated by a combination of spectroscopic analyses including HRESIMS and NMR. Compound 6 was found to be the first natural product possessing an unusual 6,6-dimethoxy-3-methylhex-2-en-1-oxyl group. These new compounds were evaluated for their cytotoxic activities against five human cancer cell lines, of which, compound 1 exhibited moderate activities with IC50 values ranging from 13.32–29.65 μM.

Brasilane sesquiterpenoids and dihydrobenzofuran derivatives from Aspergillus terreus [CFCC 81836]

Brasilanones A-F and asperterreusines A-C, undescribed brasilane sesquiterpenoids and dihydrobenzofuran derivatives, were isolated from the marine-derived fungus Aspergillus terreus [CFCC 81836]. Their structures with absolute configurations were elucidated on the basis of spectroscopic data, X-ray crystallographic analyses, and electronic circular dichroism (ECD) calculations. Brasilanones A-F are unusual brasilane sesquiterpenoids with an α,β-unsaturated ketone unit, interestingly, brasilanones B-D are stereo isomers. All of the isolates were evaluated for their inhibitory activities against NO production and cytotoxic activities against five human cancer cell lines (HL-60, SW-480, A-549, MCF-7, and SMMC-7721). Brasilanones A and E showed moderate inhibitory effect with NO inhibition rates of 47.7% (p < 0.001) and 37.3% (p < 0.001) at the concentration of 40 μM. Asperterreusines A showed cytotoxicity against HL-60 and SW-480 cell lines with IC50 values of 15.3 and 25.7 μM, respectively.

BACE1 Inhibitory Meroterpenoids from Aspergillus terreus

Sixteen 3,5-dimethylorsellinic acid-based (DMOA-based) meroterpenoids, including 10 new compounds, asperterpenes D-M (1-10), were obtained from Aspergillus terreus. The structures and absolute configurations of the new compounds were confirmed by extensive spectroscopy, single-crystal X-ray diffraction analysis, and experimental electronic circular dichroism (ECD) measurements. Compounds 2, 3, and 7 are the first 3,5-dimethylorsellinic acid-based meroterpenoids possessing a unique cis-fused A/B ring system. These new compounds were evaluated for their inhibitory activity against β-site amyloid precursor protein-cleaving enzyme 1 (BACE1). Compounds 2, 3, and 7, the first 3,5-dimethylorsellinic acid-based meroterpenoids possessing cis-fused A/B rings, exhibited significant inhibitory activities against BACE1 with IC50 values of 3.3, 5.9, and 31.7 μM, respectively.

Terrusnolides A-D, new butenolides with anti-inflammatory activities from an endophytic Aspergillus from Tripterygium wilfordii

Terrusnolides A-D (1-4), four butenolides were isolated from an endophytic Aspergillus from Tripterygium wilfordii. The structures of 1-4 were established by comprehensive spectroscopic analyses and electronic circular dichroism (ECD) calculation. It is interesting that 1 was a butenolide derived by a triple decarboxylation, while 2-4 were the metabolites with 4-benzyl-3-phenyl-5H-furan-2-one motif possessing an isopentene group fused to the benzene ring. In vitro anti-inflammatory effects of these isolates were evaluated in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. 1-4 exhibited excellent inhibitory effects on the production of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) in LPS-induced macrophages, comparable with the positive control (indomethacin). Those results indicated that, terrusnolides A-D might serve as new potential natural remedies for the treatment of inflammation.

Hyperattenins L and M, two new polyprenylated acylphloroglucinols with adamantyl and homoadamantyl core structures from Hypericum attenuatum

Hyperattenins L (1) and M (2), two new benzoylated polyprenylated phloroglucinol derivatives possessing unusual adamantyl and homoadamantyl core structures, were isolated from the aerial parts of Hypericum attenuatum. Their structures were determined by extensive NMR spectroscopic methods. Compound 1 possesses an unusual tetracyclo[6.3.1.11,10.01,5]tridecane skeleton, representing the second report of natural product with this carbon skeleton. Compound 2 features an unexpected 2,3,13-trioxapentacyclo[7.5.3.17,11.05,16.012,16]octodecane ring system formed by the fusion of 2,3,8-trioxabicyclo[4.3.1]decane moiety to the tricycle[4.3.1.13,8]undecane core. Both compounds were evaluated for their cytotoxic activities against five human cancer cell lines and compound 1 showed excellent inhibitory activities against HL-60, A-549, and MCF-7 cell lines with IC50 values of 3.86, 4.34, and 5.78μM, respectively.

(±)-Terreinlactone A, a Pair of 3-Substituted δ-Lactone Enantiomers Derived from Terrein from the Fungus Aspergillus terreus

Terreinlactone A (1a/1b), a pair of 3-substituted δ-lactone enantiomers, and terreinlactone B (2), a new biosynthetic intermediate of 1a/1b, were isolated from Aspergillus terreus, along with their biosynthetic precursor (+)-terrein (3) and (+)-isoterrein (4). Compounds 1a and 1b were separated by using a Daicel chiral-pak ASH column eluting with n-hexane-EtOH (80 : 20). The structures of 1a/1b with absolute configurations were determined by comprehensive spectroscopic analyses and electronic circular dichroic (ECD) calculations. Terreinlactone A (1) represents the first example of 1,5-seco-terrein and a biogenetic pathway is proposed from the precursor terrein via the intermediated terreinlactone B (2).