Sheng-Ge Li

Racemic alkaloids from Macleaya cordata: structural elucidation, chiral resolution, and cytotoxic, antibacterial activities

Three pairs of new enantiomeric natural alkaloids (±)-macleayins C–E (1–3), together with five pairs of known racemic alkaloids (4–8), were isolated from the aerial parts of Macleaya cordata. Compounds 1–5 were separated successfully by chiral-phase HPLC to yield optically pure isomers. However, chiral resolution of compounds 6–8 existing as racemers in the plant was unsuccessful. It is noteworthy that, macleayin C represents a novel type of hybrid composed of a dihydrobenzophenanthridine alkaloid and a phenylpropanoid. The structures including the absolute configurations of (±)-1–5 were established by detailed spectroscopic analyses and electronic circular dichroism calculations. All the isolates were evaluated for in vitro anti-tumor and antibacterial activities, and compounds (±)-4–5 exhibited potent cytotoxicity against HL-60 cell lines with IC50 values less than 3.0 μM, and compounds (±)-1–3 showed moderate cytotoxic activity. Only compound 7 revealed inhibitory activities against Staphylococcus aureus, Bacillus subtilis, and Candida albicans with MIC values of 33.07, 8.27, and 8.27 μg mL−1, respectively.

Sporulaminals A and B: a pair of unusual epimeric spiroaminal derivatives from a marine-derived fungus Paraconiothyrium sporulosum YK-03

Sporulaminals A (1) and B (2), a pair of unusual epimeric spiroaminal derivatives, bearing a 6/4/5/5 tetracyclic ring system derived from bergamotane sesquiterpenoid, were isolated from a marine-derived fungus Paraconiothyrium sporulosum YK-03. Their structures including the absolute configurations were elucidated by extensive NMR experiments, crystal X-ray diffraction and computational electronic circular dichroism (ECD) method. Furthermore, the epimerization induced by pH, temperature and H2O was revealed, together with the hypothetical biosynthetic pathway.

Phomeketales A–F, six unique metabolites from the endophytic fungus Phoma sp. YN02-P-3

Phomeketales A–F (1–6), six new xyloketals, with unprecendented carbon substitution at C-16 and C-17 simultaneously, were isolated from the endophytic fungus Phoma sp. YN02-P-3. Their structures were elucidated on the basis of 1D and 2D NMR spectral data and ECD analysis. Compound 3 exhibited moderate anti-AChE activity and cytotoxicity against HL-60.

Lignans and triterpenoids from Vitex negundo var. heterophylla and their biological evaluation

Three new phenylnaphthalene-type lignans, vitexnegheteroins E-G (1-3), and a new polyoxygenated ursane-type triterpene, vitexnegheteroin H (9), were isolated from the seeds of Vitex negundo var. heterophylla, together with ten known compounds. Their structures were established on the basis of extensive 1D and 2D NMR experiments, as well as their mass spectroscopic data. The absolute configurations of compounds 1 and 2 were determined by comparing their experimental ECD spectra with that calculated by the time-dependent density functional theory (TDDFT) method. The isolates were evaluated for their cytotoxicities against three human cancer cell lines, inhibitory activities on lipopolysaccharide-induced NO production in murine microglial BV-2 cells, and antioxidant activities for ABTS radical scavenging.

Cytotoxic quinazoline alkaloids from the seeds of Peganum harmala

Seventeen quinazoline alkaloids and derivatives, containing two pairs of new epimers, named as (S)- and (R)-1-(2-aminobenzyl)-3-hydroxypyrrolidin-2-one β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside (1, 2), (S)- and (R)-vasicinone β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside (3, 4), and a new enantiomer (12b), together with six known ones (5-8, 10, and 12a), and three pairs of known enantiomers (9, 11, and 13), were isolated from the ethanol extracts of the seeds of Peganum harmala L.. Their structures including the absolute configuration were elucidated by using 1D and 2D NMR, and ECD calculation approaches. The cytotoxic activities of all isolated compounds were evaluated. 11 showed moderate cytotoxicity against PC-3 cells with an IC50 value of 15.41 μM.

Two pairs of enantiomeric α-pyrone dimers from the endophytic fungus Phoma sp. YN02-P-3

(±) Phomones A (1) and B (2), two pairs of novel enantiomeric α-pyrone dimers from the endophytic fungus Phoma sp. YN02-P-3 are reported. Compounds 1 and 2 are the first examples of 6-α,β-unsaturated ester-2-pyrone dimers, and compound 1 possesses a novel 6/4/5/6 tetracyclic ring system. Their structures and stereochemistry were determined by the analysis of extensive spectroscopic data, ECD calculations and single-crystal X-ray diffraction data.

Bioactive terpenoids from Silybum marianum and their suppression on NO release in LPS-induced BV-2 cells and interaction with iNOS

Three new (1-3) and one known (4) bioactive terpenoids were isolated from the seeds of Silybum marianum based on the investigation to get new NO inhibitors. Their structures were determined by extensive NMR (1D and 2D NMR) and MS spectroscopic data, and the absolute configurations were identified by experimental and calculated ECD spectra. The NO inhibitory activities in murine microglial BV-2 cells and interactions with iNOS protein by molecular docking were evaluated for all compounds. The results showed that these compounds had potent NO inhibitory effects.

Bioassay- and Chemistry-Guided Isolation of Scalemic Caged Prenylxanthones from the Leaves of Garcinia bracteata

With bioassay- and chemistry-guided fractionation, seven new caged prenylxanthones including two scalemic mixtures, epiisobractatin (1), 13-hydroxyisobractatin (2), 13-hydroxyepiisobractatin (3), 8-methoxy-8,8a-dihydrobractatin (4), 8-ethoxy-8,8a-dihydrobractatin (5), garcibracteatone (6), and 8-methoxy-8,8a-dihydroneobractiatin (7), and the eight known compounds 8-15 were isolated from the leaves of Garcinia bracteata. The structures were unambiguously elucidated through analysis of spectroscopic data. The 2D structures and relative configurations of 1 and 5 were confirmed by X-ray crystallographic analysis. The separation of the enantiomers of 1-5 was accomplished by chiral-phase HPLC. The absolute configurations of the enantiomers of 1 and 5 were assigned by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. The absolute configurations of the related compounds were determined via comparisons of their ECD data with those of the enantiomers of 1 and 5, respectively. Notably, compound 7, with a neo caged skeleton, is the first representative of a novel type of caged xanthone lacking a Δ8(8a) double bond. The isolated compounds exhibited significant cell growth inhibitory activities in vitro against human leukemic HL-60 and K562 cell lines, with GI50 values ranging from 0.2 to 8.8 μM. A preliminary structure-activity relationship is discussed.

Racemic indole alkaloids from the seeds of Peganum harmala

Five pairs of new 2-oxoindole alkaloids, (±)-peganumalines A-E (1-5), and a new indole alkaloid, peganumaline F (6), along with two known analogues, were isolated from the seeds of Peganum harmala. Their structures and absolute configurations were elucidated through spectroscopic analyses and quantum chemistry calculations. Notably, (±)-peganumalines A (1) represent a pair of rare 2-oxoindole dimeric alkaloid enantiomer with the hitherto unknown carbon skeleton. All isolates were tested for antiproliferative and antibacterial activities.

LC-MS guided isolation of three pairs of enantiomeric alkaloids from Macleaya cordata and their enantioseparations, antiproliferative activity, apoptosis-inducing property

Abstract(±)-Macleayins F–H (1–3), three pairs of new enantiomeric alkaloid dimers, along with four known alkaloids (4–7) as their plausible biogenetic precursors, were isolated from the aerial parts of Macleaya cordata. Compounds 1–3 were obtained under the guidance of LC-MS investigation, and their structures were elucidated by analysis of the 1D and 2D NMR spectroscopic data. The racemic mixtures were successfully separated by chiral HPLC, and the absolute configurations of enantiomers were determined by electronic circular dichroism (ECD) spectroscopy. Compounds 1–7 showed antiproliferative activity against HL-60 with IC50 values of 1.34–41.30 μM, especially compounds 1–2 exhibited the best inhibitory activity against HL-60 cell lines. In addition, the preliminary mechanism investigation for compound 2 using Annexin V/7-AAD double-staining assay, DAPI staining assay and JC-1 staining method, indicated that 2 inhibited cancer cell proliferation potentially through inducing apoptosis via the mitochondria-related pathway and arrested cell cycle of HL-60 cells at S phase.