Xiao-Jun Huang

Flueggines A and B, Two New Dimeric Indolizidine Alkaloids from Flueggea virosa

Two unprecedented C,C-linked dimeric indolizidine alkaloids, flueggines A (1) and B (2), were isolated from the twigs and leaves of Flueggea virosa. The structures and absolute configurations were elucidated by means of NMR, single-crystal X-ray diffraction, and CD analyses. Compound 1 is the first example of Securinega alkaloids bearing an isoxazolidine ring, the plausible biogenetic pathway of which is also proposed. Compound 2 exhibited growth inhibitory activity against MCF-7 and MDA-MB-231 human breast cancer cells.

Virosaines A and B, two new birdcage-shaped Securinega alkaloids with an unprecedented skeleton from Flueggea virosa.

Two new Securinega alkaloids, virosaines A (1) and B (2), were isolated from the twigs and leaves of Flueggea virosa. The structures and absolute configurations were elucidated by means of NMR, X-ray diffraction, and CD analyses. Compounds 1 and 2 represent the first examples of Securinega alkaloids bearing a 7-oxa-1-azabicyclo[3.2.1]octane ring system, whose plausible biogenetic pathways were also proposed.

Purpurogemutantin and Purpurogemutantidin, New Drimenyl Cyclohexenone Derivatives Produced by a Mutant Obtained by Diethyl Sulfate Mutagenesis of a Marine-Derived Penicillium purpurogenum G59

Two new drimenyl cyclohexenone derivatives, named purpurogemutantin (1) and purpurogemutantidin (2), and the known macrophorin A (3) were isolated from a bioactive mutant BD-1-6 obtained by random diethyl sulfate (DES) mutagenesis of a marine-derived Penicillium purpurogenum G59. Structures and absolute configurations of 1 and 2 were determined by extensive spectroscopic methods, especially 2D NMR and electronic circular dichroism (ECD) analysis. Possible biosynthetic pathways for 1–3 were also proposed and discussed. Compounds 1 and 2 significantly inhibited human cancer K562, HL-60, HeLa, BGC-823 and MCF-7 cells, and compound 3 also inhibited the K562 and HL-60 cells. Both bioassay and chemical analysis (HPLC, LC-ESIMS) demonstrated that the parent strain G59 did not produce 1–3, and that DES-induced mutation(s) in the mutant BD-1-6 activated some silent biosynthetic pathways in the parent strain G59, including one set for 1–3 production.

Guadial A and Psiguadials C and D, Three Unusual Meroterpenoids from Psidium guajava

The first monoterpene-based meroterpenoid (1) and two novel sesquiterpene-based ones (2 and 3) with unprecedented skeletons were isolated from the leaves of Psidium guajava. Their structures with absolute configuration were elucidated by extensive spectroscopic studies. A plausible biosynthetic pathway for all meroterpenoids from the title plant is also proposed. Compounds 2 and 3 showed significant cytotoxicity toward HepG2 and HepG2/ADM cells.

Callistrilones A and B, Triketone-Phloroglucinol-Monoterpene Hybrids with a New Skeleton from Callistemon rigidus.

The first triketone-phloroglucinol-monoterpene hybrids, callistrilones A and B (1 and 2), along with a postulated biosynthetic intermediate (3) were isolated from the leaves of Callistemon rigidus. Compounds 1 and 2 featured a new carbon skeleton with an unprecedented [1]benzofuro[2,3-a]xanthene or [1]benzofuro[3,2-b]xanthene pentacyclic ring system composed of three kinds of building blocks. Their structures and absolute configurations were elucidated by spectroscopic analysis, X-ray diffraction, and electronic circular dichroism (ECD) calculations. A plausible biogenetic pathway for the new compounds is also proposed. Compound 1 exhibited moderate antibacterial activity against Gram-positive bacteria including multiresistant strains.

Dysideanones A-C, unusual sesquiterpene quinones from the South China Sea sponge Dysidea avara.

Dysideanones A-C (1-3), three unusual sesquiterpene quinones with unprecedented carbon skeletons, were isolated from the South China Sea sponge Dysidea avara. Their structures including absolute configurations were determined by a combination of spectroscopic analyses and calculated ECD spectra. Within the sesquiterpene quinone structures, dysideanones A (1) and B (2) share an unprecedented 6/6/6/6-fused tetracyclic carbon skeleton, while dysideanone C (3) possesses an unusual 6/6/5/6-fused tetracyclic core. Dysideanone B (2) showed cytotoxicity against two human cancer cell lines, HeLa and HepG2, with IC50 values of 7.1 and 9.4 μM, respectively.

Flavone C-glycosides from the Leaves of Lophatherum gracile and Their In Vitro Antiviral Activity

Four new flavone C-glycosides, luteolin 6-C-α-L-arabinopyranosyl-7-O-β-D-glucopyranoside, apigenin 6-C-β-D-galactopyranosiduronic acid (1 → 2)-α-L-arabinopyranoside, luteolin 6-C-β-D-galactopyranosiduronic acid (1 → 2)-α-L-arabinopyranoside, and luteolin 6-C-β-D-glucopyranosiduronic acid (1 → 2)-α-L-arabinofuranoside, along with three known ones, were isolated from the leaves of Lophatherum gracile. The structures of the new compounds were elucidated by extensive spectroscopic methods as well as acid hydrolysis. All the flavone glycosides isolated from this plant were screened for their in vitro antiviral activity against respiratory syncytial virus (RSV) with cytopathic effect (CPE) reduction assay, and several flavone 6-C-monoglycosides showed potent in vitro anti-RSV effect.

Iboga-Type Alkaloids from Ervatamia officinalis.

Seven new iboga-type alkaloids, ervaoffines A-D (1-4), (7S)-3-oxoibogaine hydroxyindolenine (5), ibogaine-5,6-dione (6), and 19-epi-5-oxovoacristine (7), and 10 known alkaloids were isolated from Ervatamia officinalis. The absolute configurations of 1-7 were determined through X-ray diffraction and electronic circular dichroism (ECD) analyses. Ervaoffines A and B represent the first iboga-type pseudoindoxyl alkaloids in which the C-2 spiro carbon configuration is opposite to that of other members of this class, such as iboluteine (8). The relationship between the absolute configuration of the spiro carbons and the Cotton effect in the ECD spectrum is established for the first time for iboga-type pseudoindoxyl and oxindole alkaloids. Additionally, a plausible biogenetic pathway for these alkaloids is proposed.

Cytotoxic dimeric indole alkaloids from Catharanthus roseus

Three new dimeric indole alkaloids (1-3), together with five known ones (4-8), were isolated from the whole plants of Catharanthus roseus. The structures and absolute configurations of new compounds were elucidated by means of NMR and CD analyses. All these compounds were evaluated for their in vitro cytotoxic activities against human breast cancer cell line MDA-MB-231.

Metabolic differentiations of Pueraria lobata and Pueraria thomsonii using 1H NMR spectroscopy and multivariate statistical analysis

Puerariae Radix was a widely used herbal medicine. Pueraria lobata (PL) and Pueraria thomsonii (PT) were the two authorized sources of Puerariae Radix (gegen) in China. In this study, metabolic differentiations between these two species were investigated using NMR spectroscopy followed by principal components analysis (PCA) and partial least squares-discriminant analysis (PLS-DA). The content of puerarin in PL and PT was also determined using quantitative (1)H NMR spectroscopy. Thirteen isoflavones were tentatively identified based on 1D and 2D NMR spectroscopic data in two species. The (1)H NMR spectra of PL and PT were obviously different. PL and PT could also be markedly discriminated from (1)H NMR spectroscopic data by PCA and PLS-DA. For the crude drug resources, isoflavones, in which puerarin is the most important one, were regarded as the reasonable markers for the discrimination of the two species. The contents of puerarin and total isoflavones in PL were quantitated much higher than those in PT. Above all, (1)H NMR spectroscopy, which can provide comprehensive profiles of the metabolites and achieve convenient determinations of puerarin and total isoflavones in a single run, is an efficient means for evaluating the medicinal samples and achieving a better quality control of Puerariae Radix.