KF-catalyzed direct thiomethylation of carboxylic acids with DMSO to access methyl thioesters.

With dimethyl sulfoxide (DMSO) as the methylthio source, a KF-catalyzed strategy was employed for the direct thiomethylation of carboxylic acids with DMSO for the preparation of methyl thioesters. In this process, a wide range of methyl thioesters were obtained in moderate to excellent yields. This novel strategy features the first use of DMSO as a methylthiolating agent for the construction of methyl thioesters, transition metal-free conditions, inexpensive reagents, easy workup, broad substrate scope and sustainability. Additionally, this procedure can be readily scaled up to a gram scale.

Dimethylated acylphloroglucinol meroterpenoids with anti-oral-bacterial and anti-inflammatory activities from Hypericum elodeoides.

Acylphloroglucinol meroterpenoids are adducts of the acylphloroglucinol unit and polyprenylated fragments (terpenoids) with attractive structures and bioactivities. During study of the medicinal molecules of the genus Hypericum, the first example of dimethylated acylphloroglucinol meroterpenoids with pyran-fused 6/6/6 tricyclic skeletons ((+)/(-)-elodeoidols A-F (1-6)), along with three biogenetical homologues (7-9) were isolated from the herbaceous plant of Hypericum elodeoides. Their structures including absolute configurations were then identified by nuclear magnetic resonance (NMR), high resolution electrospray ionization mass spectroscopy (HRESIMS), electronic circular dichroism (ECD) analysis and calculations. The monoterpene moiety of 1-6 were cyclized as two cyclohexanes and fused with a dimethylated acylphloroglucinol unit through an additional ether linkage, which led to an interesting pyran-fused linear or angle type 6/6/6 tricyclic skeleton. Compounds 5, 8 and 9 showed preferable antibacterial activities against three oral bacteria, among the MIC value of (+)-5 was 6.25 µg/ml; Compounds 3, 7 and 8 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells (IC50: 10.39 ± 0.49 ~ 34.25 ± 2.32 µM).

Two new bioactive diterpenes identified from Isodon interruptus.

In the course of our ongoing studies to discover bioactive chemical constituents from plants in the genus Isodon, two new diterpenes, kunminolide A (1) and rabdokunmin F (2) were isolated from the leaves of the medicinal plant Isodon interruptus. Kunminolide A (1) is a novel abietane-like diterpene with a novel skeleton, herein designated as 9, 10-seco-neoabietane. Rabdokunmin F (2) is an ent-kaurene diterpene with C-18 oxidized to a carboxylic acid group. The structures were determined by spectroscopic means including analysis of 1D- and 2D-NMR spectral data. Crystals of 1 obtained from methanol were suitable for X-ray analysis, which confirmed the chemical structure. Kunminolide A (1) demonstrated chemopreventive potential by inducing QR1 activity with a CD value of 14.3 µM, and rabdokunmin F (2) was found to have cytotoxic activities with IC50 values in the range of 1.1-3.0 µM.

[A new macrocyclic phenolic glycoside from Sorghum vulgare root].

Eleven compounds were isolated and purified from Sorghum vulgare root extract, through column chromatography over silica gel, MCI gel, and preparative HPLC. Their structures were established by MS, 1 D NMR and 2 D NMR data as sorgholide A(1), ß-sitosterol(2), stigmastero(3), daucosterol(4), 4-methoxycinnamic acid(5), taxiphyllin(6), chlorogenic acid(7), p-hydroxybenzaldehyde(8), succini acid(9), trans-p-hydroxycinnamic acid(10), obtusalin(11). Compounds 4,5 and 9-11 were reported from this species for the first time, and compound 1 is the first 24 ring dimeric double lactonol glycoside formed by reverse polymerization of p-hydroxyphenylacetate glucoside, named sorgholide A.

1α,2α-Epoxy-3ß-hydroxy oleanolic acid derivatives regulation of the metabolism, haemolysis and ß-lactamase gene expression in vitro and their structure-microbicidal activity relationship.

Oleanolic acid (OA), one of the major pentacyclic triterpenes abundantly present in nature, is a promising compound with various biological activities, including anti-inflammatory, anti-ulcer, hepatoprotective, antidiabetic, fungicidal and antiparasitic properties. Therefore, a series of derivatives of 1α,2α-epoxy-3ß-hydroxyl oleanolic acid derivatives were designed and synthesized, and their antibacterial activities were investigated in vitro. Based on these results, the compounds with antibacterial activity were screened by RT-PCR to determine whether they can regulate the expression of genes related to metabolism, haemolysis, and ß-lactamase in vitro, and the structure-microbicidal activity relationship of each compound was analyzed. Our study shows that some of the modifications in the synthetic compounds, such as the introduction of an ortho-cyano-substituted benzyl group and a short chain alkyl ester at the 28-carboxyl, as well as the introduction of an acetyl group at the 3-hydroxyl group of ring A, could enhance antibacterial activity. This provides basic evidence for the optimization of 1α,2α-epoxy-3ß-hydroxyl oleanolic acid derivatives. The antibacterial mechanism of the active OA derivatives appears to involve the regulation of expression of metabolism-associated genes in Escherichia coli, haemolysis-associated genes in Bacillus subtilis, metabolism-related genes in Klebsiella pneumonia and ß-lactamase-associated genes in Acinetobacter baumannii. Some OA derivatives were bactericidal to three of the strains and appeared to regulate gene expression associated with metabolism, haemolysis, and ß-lactamase in vitro. These newly designed OA derivatives possess unique antibacterial activities and may be potentially useful for prophylactic or therapeutic intervention of bacterial infections.

18ß-Glycyrrhetinic Acid Derivatives Possessing a Trihydroxylated A Ring Are Potent Gram-Positive Antibacterial Agents.

The oleanane-type triterpene 18ß-glycyrrhetinic acid (1) was modified chemically through the introduction of a trihydroxylated A ring and an ester moiety at C-20 to enhance its antibacterial activity. Compounds 22, 23, 25, 28, 29, 31, and 32 showed more potent inhibitory activity against Streptomyces scabies than the positive control, streptomycin. Additionally, the inhibitory activity of the most potent compound, 29, against Bacillus subtilis, Staphylococcus aureus, and methicillin-resistant Staphylococcus aureus was greater than that of the positive controls. The antibacterial mode of action of the active derivatives involved the regulation of the expression of genes associated with peptidoglycans, the respiratory metabolism, and the inherent virulence factors found in bacteria, as determined through a quantitative real-time reverse transcriptase PCR assay.

[Chemical constituents from medical and edible plants of Rosa roxburghii].

Rosa roxburghii, a kind of the medical and edible plants belonging to the Rosaceae family, is widely distributed in the southwest districts of China, especially Guizhou province. Now, by reason of the extensive bioactivities, the plant is widely used in the field of food, health product, drug, and so on. In the course of our continuing search for the bioactive constituents, thirteen compounds were isolated from R. roxburghii, and their structures were determined on the basis of physicochemical property, spectroscopic data and comparison with the literatures, as 2-oxo pomolic acid(1), 1ß-hydroxyeuscaphic acid(2), euscaphic acid(3), arjunic acid(4), tormentic acid(5), kaiiichigeside F1(6), rosamultin(7), arjunetin(8), 2ɑ, 3ɑ, 19ɑ-trihydroxy-olean-12-en-28-oic acid 28-O-ß-D-glucopyranoside(9), 2α, 3α, 19α, 24-tetrahydroxyolean-12-en-28-oic-acid 28-O-ß-D-glucopyranosyl ester(10), pyrogallic acid (11), daucosterol(12), and 1, 2-decanediol(13). Compounds 9 and 10 were firstly obtained from Rosaceae family, and compounds 1,4,5,9-11,13 were isolated from this plant for the first time.

Two new coumarin glycosides from Chimonanthus nitens.

Two new coumarin glycosides, namely nitensosides A-B (1-2), together with six known compounds, scopolin (3), 5,6,7-trimethoxycoumarin (4), d-calycanthine (5), calycanthoside (6), xeroboside (7), and scopoletin (8), were isolated from Chimonanthus nitens. The structures of the new compounds were elucidated by comprehensive analysis of IR, MS, and NMR spectroscopic data. Compounds 3, 4, 7, and 8 showed moderate inhibitory activity against Micrococcus luteus.

Cinnamigones A-C, three highly oxidized guaiane-type sesquiterpenes with neuroprotective activity from Cinnamomum migao.

Cinnamigones A-C, three undescribed highly oxidized guaiane-type sesquiterpenes were isolated from the fruits of Cinnamomum migao. Cinnamigone A (1), structurally artemisinin-like, is a natural 1,2,4-trioxane caged endoperoxide with an unprecedented tetracyclic 6/6/7/5 ring system. Compounds 2-3 are classic guaiane sesquiterpene featuring different epoxy units. Guaiol (4) is considered to be the precursor of 1-3 in the biosynthesis pathway hypothesis. The planar structures and configurations of cinnamigones A-C were elucidated by spectral analysis, HRESIMS, X-ray crystallography and ECD calculations. Evaluation of the neuroprotective activity of 1-3 on N-methyl-ᴅaspartate (NMDA) toxicity was demonstrated that compounds 1-2 exhibited moderate neuroprotective activity against NMDA-induced neurotoxicity.

Potential antiplatelet aggregation metabolites from the discarded sorghum (Sorghum bicolor L.) root.

Sorghum (Sorghum bicolor L.) is the fifth largest crop in the world and has potential health benefits, but vast quantities of sorghum roots are discarded after harvest. Based on the previous antiplatelet aggregation for this species, two new multi-substituted 3H-indole alkaloids sorghumine A (1) and sorghumine B (2), together with 14 known compounds (3-16), were found from the water extract of sorghum roots. Compounds 1-2 were identified by analyzing their spectroscopic data and physic and chemical properties, and the absolute configuration was further determined by electronic circular dichroism (ECD) analysis and calculations. 1-2, 4, 6-8 and 13-15 showed significant inhibition of platelet aggregation induced by adenosine diphosphate. 2-4, 6-9 and 11 showed significant inhibition of platelet aggregation induced by collagen. 4-6, 8, 10-11 and 16 showed significant inhibition on platelet aggregation induced by thrombin. Furthermore, molecular docking showed that active compounds can bind to P2Y12 and COX-1 receptors in platelet.

Discovery of antifungal constituents from the Miao medicinal plant Isodon flavidus.

ETHNOPHARMACOLOGICAL RELEVANCE: Leigong Mountain is an area in the Southwest of China where there is a high incidence rate of athlete's foot, but the Miao people, a Chinese minority who reside in this mountainous area have suffered less from this disease due to their use of the herbal medicine Isodon flavidus (Hand.-Mazz.) H. Hara. AIM OF THE STUDY: The present study is to identify the active chemical constituents responsible for antifungal effects of the folk medicine plant. MATERIALS AND METHODS: The natural compounds were separated from the methanol extract of the twigs and leaves of I. flavidus by phytochemical study using chromatographic methods, and their chemical structures were determined by analysis of the spectroscopic data including 1D and 2D NMR spectra. The absolute configuration of fladin A (1) was further confirmed by X-ray crystallographic analysis. The compounds were evaluated for their antifungal activity against the athlete's foot fungus Trichophyton rubrum. They were further evaluated for their antimicrobial and anti-biofilm activity against the dental pathogens Streptococcus mutans, Porphyromonas gingivalis and Candida albicans. RESULTS: Phytochemical and biological studies of I. flavidus led to the discovery of two antifungal compounds, fladin A (1) and lophanic acid (2). Fladin A (1) is a novel diterpene with an unprecedented cyclic ether group formed between C-4 and C-9. Lophanic acid (2) displayed inhibition activity against the athlete's foot fungus Trichophyton rubrum with an MIC value of 7.8µg/mL, and fladin A (1) also showed inhibition activity against the fungus with a MIC value of 62.5µg/mL. CONCLUSIONS: Our identification of two antifungal compounds provided strong evidence for the Miao people to use I. flavidus as a medicinal plant for treatment of athlete's foot disease. The very different chemical structures of the active compounds from those in the market presents them as potential antifungal lead compounds for follow-up study.