Four new minor alkaloids from the seeds of Strychnos nux-vomica

Four new minor alkaloids, stryvomicine A (1), deoxy-isostrychnine-chloromethochloride (2), β-colubrine-chloromethochloride (3) and α-colubrine-chloromethochloride (4) were isolated from the seeds of Strychnos nux-vomica. Stryvomicin A possesses an unprecedented 6/5/7/8/6/7/6 heptacyclic ring system, which is the first example of the linkage of the C3–O–C26–N4 bond in strychnan-type alkaloids. Compound 5 induced the occurrence of autophagy and might have potential implications in autophagy related diseases.     

Structures of new alkaloids sessilifoliamides A-D from Stemona sessilifolia

Four new Stemona alkaloids, sessilifoliamides A-D (1-4), were isolated from the roots of Stemona sessilifolia, along with five known alkaloids, stenine (5), 2-oxostenine (6), stemoninoamide (7), tuberostemonone (8), and neotuberostemonol (9). The structures and absolute configurations of the new alkaloids were determined by the spectral studies (HRMS, IR, ¹H, ¹³C, and 2D NMR), single-crystal X-ray analyses, and chemical correlations. The absolute configuration of 7 was also determined by the modified Mosher's method.     

New alkaloids sinomacutines A–E,and cephalonine-2-O-β-d-glucopyranoside from rhizomes of Sinomenium acutum

Phytochemical investigation on the rhizomes of Sinomenium acutum led to the isolation of new alkaloids sinomacutines A–E (1–5), and cephalonine-2-O-β-d-glucopyranoside (6), along with known tetrahydroisoquinoline alkaloids (7–9). Among them, sinomacutines A–C were new bistetrahydroisoquinoline alkaloids with morphinane–proaporphine and morphinane–benzyltetrahydroisoquinoline types, and coupled with unique C–CH₂–N unit. Their structures with absolute configuration were elucidated on the basis of 1D and 2D NMR, and ECD spectra analysis. The new compounds were evaluated for their anti-inflammatory and cytotoxic activities, and sallisonine B (2) showed moderate ability to inhibit NO production of LPS-stimulated RAW264.7 macrophages, as well as sallisonine A (1) showed weak inhibitory effects against five cancer cell lines.     

Guignardins A–F,spirodioxynaphthalenes from the endophytic fungus Guignardia sp. KcF8 as a new class of PTP1B and SIRT1 inhibitors

Six new guignardins A–F (1–6) were isolated from the cultures of endophytic fungus Guignardia sp. KcF8 derived of a mangrove plant Kandelia candel, along with three known analogues, palmarumycins C₁ (7), BG1 (8), and JC1 (9). Compounds 2, 3, 7, and 8 showed antimicrobial activities. Compounds 5–7 exhibited significant cytotoxicities against 10 human tumor cell lines. Compound 3 also displayed significant inhibitory activity against human protein tyrosine phosphatase 1B and histone deacetylase silent information regulator T1enzymes, two key targets for the treatment of diabetes. This is the first report on the anti-PTP1B and anti-SIRT1 activities of spirodioxynaphthalenes.     

Hyrtimomines,indole alkaloids from Okinawan marine sponges Hyrtios spp.

Six new indole alkaloids, hyrtimomines F–K (1–6), were isolated from Okinawan marine sponges Hyrtios spp. The structures of 1–6 were elucidated on the basis of spectroscopic analysis. Hyrtimomine F (1) is a structurally unique bisindole alkaloid possessing an α-keto-?-caprolactam ring, while hyrtimomine G (2) is a symmetrical bisindole alkaloid. Hyrtimomines H–K (3–6) are indole alkaloids possessing β-carboline skeleton with an imidazolium unit. Antimicrobial activities of hyrtimomines F–K (1–6) were evaluated.     

New pyridoacridine alkaloids from the purple morph of the ascidian Cystodytes dellechiajei

Two new pyridoacridine alkaloids, 13-didemethylaminocycloshermilamine D (1) and demethyldeoxyamphimedine (2), were isolated from the purple chromotype of the Western Mediterranean ascidian Cystodytes dellechiajei. This morph also contained the known shermilamine B (3), kuanoniamine D (4), N-deacetylshermilamine B (5), N-deacetylkuanoniamine D (6), styelsamines C (7), and D (8). The structures of new compounds were elucidated on the basis of spectroscopic data. A hypothetic biosynthetic pathway from the tetracyclic styelsamine D (8) was proposed for both compounds 1 and 2 and their antimicrobial potential was evaluated.     

Aigialomycins and related polyketide metabolites from the mangrove fungus Aigialus parvus BCC 5311

Reinvestigation of the secondary metabolites from the marine mangrove fungus Aigialus parvus BCC 5311 led to the isolation of six new nonaketide metabolites, aigialomycins F (4) and G (5a/5b), 7′,8′-dihydroaigialospirol (7), 4′-deoxy-7′,8′-dihydroaigialospirol (8), and rearranged macrolides 9 and 10, along with six previously described compounds, hypothemycin (1), aigialomycins A (2) and B (3), aigialospirol (6), 4-O-demethylhypothemycin (11), and aigialone (12). The structures of the new compounds were elucidated by analyses of the NMR spectroscopic and mass spectrometry data in combination with chemical means.     

Diterpenes and sesquiterpenes with anti-Coxsackie virus B3 activity from the stems of Illicium jiadifengpi

Seven new diterpenes, jiadifenoic acids J–P (1–7), two new sesquicarane sesquiterpenes, sesquicaranoic acids A and B (8 and 9), and four known compounds, were isolated from the stems of Illicium jiadifengpi. The trans-fused A/B ring junction in diterpenes was deduced from NMR data analysis and confirmed by single-crystal X-ray crystallography of 3. The absolute configurations of compounds 1 and 5 were determined using the Mo₂(OAc)₄-induced circular dichroism (ICD) method. Compounds 8 and 9 are a pair of C-10 epimers, and their absolute configurations were confirmed by analyzing their CD and ICD data. All of the isolated compounds were evaluated in vitro for their antiviral activities against Coxsackie virus B3 (CVB3). Among the isolated compounds, 4, 5, 7, 10, and 11 exhibited reasonable activity against CVB3, with IC₅₀ values of 7.0–22.2 μmol/mL and selective index values (SI=TC₅₀/IC₅₀) of 49.3, 37.1, 31.3, 45.6 and 40.9, respectively.     

Nortriterpenoids from Schisandra chinensis and their absolute configurational assignments by electronic circular dichroism study

Twelve new nortriterpenoids, namely wuweizidilactones J–P (1–7), schindilactones I–K (8–10), preschisanartanin N (11), and schisdilactone J (12), as well as 23 known analogues, were isolated from the leaves and stems of Schisandra chinensis. The absolute configurations of 1 and 11 were established by calculated electronic circular dichroism (ECD) spectra and that of 7 was confirmed by single-crystal X-ray diffraction. The absolute configurations of 2–6, 8, and 9 were determined by an empirical comparison of their experimental ECD spectra with that of 1. It is the first time that the ECD spectra of 18(13→14)-abeo-schiartane-, 18-norschiartane-, and schisanartane-type nortriterpenoids possessing an α,β-unsaturated-γ-lactone moiety are presented, this method providing an alternative means of obtaining absolute configurational assignments for these types of nortriterpenoids. All isolates were evaluated for their anti-acetylcholinesterase and anti-butyrylcholinesterase activities, and compounds 8, 13, 23, and 31 show anti-acetylcholinesterase activity at concentrations of 50 μM, with 12.7, 10.7, 16.6, and 32.1% inhibition, respectively.     

Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.

Chemical investigation of a southern Australian sponge, Pseudoceratina sp., resulted in the isolation of twelve bromotyrosine-derived alkaloids, comprising four new metabolites, aplysamine-7 (1), (−)-purealin B (2), purealin C (3) and purealin D (4); two new spiroisoxazole enantiomers, (−)-purealidin R (5) and (−)-aerophobin-2 (6); five known metabolites (−)-pseudoceratinine A (7), (−)-aeroplysinin-1 (8), aplysamine-2 (9), purpuramine G (10) and purpuramine J (11); and an artifact 12 derived from ethanolysis of 5. Structures for 1-12 were assigned on the basis of detailed spectroscopic analysis. A second southern Australian Pseudoceratina sp. afforded the first recorded account of a racemic bromotyrosine-derived spiroisoxazole, (±)-purealin (13b), together with the known achiral precursor purealidin A (15). A literature review of marine bromotyrosine-derived spiroisoxazoles reaffirmed the published dominance of (+)-spiroisoxazoles, acknowledging several accounts of (−)-spiroisoxazoles, while also revealing a wide range of chiroptical measurements suggestive of variable optical purity. The Pseudoceratina sp. metabolites 1-12, 13b and 15 were assessed for antibiotic properties, with the new metabolites 3 and 13b exhibiting broad spectrum activity against several Gram-positive bacteria.     

Polyketides from the mangrove-derived endophytic fungus Acremonium strictum

Five new polyketide derivatives, 6′-hydroxypestalotiopsone C (1), acropyrone (2), bicytosporone D (3), waol acid (4), and pestalotiopene C (5), together with seven known metabolites (6–12), were obtained from extracts of the endophytic fungus Acremonium strictum, isolated from the mangrove tree Rhizophora apiculata. The structures of the isolated compounds were elucidated on the basis of comprehensive NMR and MS analysis. Compounds 6, 7, and 9 showed moderate cytotoxic activity against human cisplatin-sensitive (IC₅₀ values 27.1, 76.2, and 8.3 μM, respectively) and resistant A2780 cell lines (IC₅₀ values 12.6, 30.1, and 19.0 μM, respectively), whereas only 9 exhibited antibacterial activity against Staphylococcus aureus (MIC value 14.3 μM).     

Sesquiterpenoids from Ligularia virgaurea spp. oligocephala

Four novel eremophilane-type sesquiterpene lactones, 6β,10α-dihydroxy-1-oxoeremophila-7(11),8(9)-dien-12,8-olide (1), 6β-acetyl-2-oxoeremophila-1(10),7(11), 8(9)-trien-12,8-olide (2), 6β,8β-diacetyl-2-oxoeremophila-1(10),7(11)-dien-12,8-olide (3), dimeric eremophilane ligulolide B (5), and known sesquiterpenoid, 6β,8α-diacetyleremophila-1(10),7(11)-dien-12,8-olide (4), were isolated from an extract of the whole plant of Ligularia virgaurea spp. oligocephala. The structure of 1 was confirmed by NMR spectra and single crystal X-ray crystallography investigation, as well as 2, 3, and 5 were elucidated by spectroscopic methods including 1D and 2D NMR spectra. A discussion of biogenesis of 5 was described. Cytotoxicities of compound 1 were measured in vitro against selected cancer cells human promyelocytic leukemia (HL-60), human ovarian (HO-8910) and human lung epithehial (A-549).     

Three new sulfur-containing alkaloids, polycarpaurines A, B, and C, from an Indonesian ascidian Polycarpa aurata

Three new sulfur-containing alkaloids, polycarpaurines A (1), B (2), and C (3) were isolated from the tropical ascidian Polycarpa aurata collected in Indonesia, together with six known compounds (4-9). The structures of new compounds were assigned on the basis of their spectral data. Compounds 1, 3, 4, and 8 inhibited colony formation of Chinese hamster V79 cells with EC₅₀ values of 6.8, 8.6, 3.8, and 10 μM, respectively. Compounds 2 and 7 showed modest activity against V79 cells (EC₅₀>10 μM).     

Novel grayanane diterpenoids from Rhododendron principis

Six new grayanane diterpenoids, principinols A–F (1–6), were isolated from Rhododendron principis. Compounds 1 and 2 possess unprecedented 6,10-epoxy and 5α-OH moieties, and 1 and 3 are the first two examples of 9α-H in grayanoids. Their structures were determined by extensive spectroscopic analysis, and the absolute configurations of 1–4 were assigned by single-crystal X-ray crystallography. Compounds 4 and 5 inhibit PTP1B phosphatase activity in vitro. A preliminary structure–activity relationship discussion is presented.     

Cyclooxygenase-2 enzyme inhibitory withanolides from Withania somnifera leaves

Four novel withanolide glycosides and a withanolide have been isolated from the leaves of Withania somnifera. The structures of the novel compounds were elucidated as physagulin D (1→6)-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (1), 27-O-β-d-glucopyranosyl physagulin D (2), 27-O-β-d-glucopyranosyl viscosalactone B (3), 4,16-dihydroxy-5β, 6β-epoxyphysagulin D (4), and 4-(1-hydroxy-2,2-dimethylcyclo-propanone)-2,3-dihydrowithaferin A (5) on the basis of 1D-, 2D NMR and MS spectral data. In addition, seven known withanolides withaferin A (6), 2,3-dihydrowithaferin A (7), viscosalactone B (8), 27-desoxy-24,25-dihydrowithaferin A (9), sitoindoside IX (10), physagulin D (11), and withanoside IV (12) were isolated. These withanolides were assayed to determine their ability to inhibit cycloxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes and lipid peroxidation. The withanolides tested, except compound 9, showed selective COX-2 enzyme inhibition ranging from 9 to 40% at 100 μg/ml. Compounds 4, 10 and 11 also inhibited lipid peroxidation by 40, 44 and 55%, respectively. The inhibition of COX-2 enzyme by withanolides is reported here for the first time.     

New polyesters from Talaromyces flavus

Six new polyesters, talapolyesters A–F (1–4, 14, and 16), together with 11 known ones 15G256ν (5), 15G256ν-me (6), 15G256π (7), 15G256β-2 (8), 15G256α-2 (9), 15G256α-2-me (10), 15G256ι (11), 15G256β (12), 15G256α (13), 15G256α-1 (15), and 15G256ω (17), were isolated from the wetland soil-derived fungus Talaromyces flavus BYD07-13, and their structures were determined by NMR and MS spectroscopic data. Among them, 1–4 and 16 were assembled in a different manner from that of the known 256 polyesters. All the polyesters are composed of (R)-2,4-dihydroxy-6-(2-hydroxypropyl)benzoic acid and (R)-3-hydroxybutyric acid/(S)-3,4-dihydroxybutyric acid residues. The absolute configurations of the residues were determined by alkaline hydrolysis. The cytotoxicity against five tumor cell lines of these compounds was examined, and a tight structure–activity relationship is proposed.     

Further studies on the constituents of the gorgonian octocoral Pseudopterogorgia elisabethae collected in San Andrés and Providencia islands, Colombian Caribbean: isolation of a putative biosynthetic intermediate leading to erogorgiaene

Chemical investigations of the MeOH-CH₂Cl₂ extract of Pseudopterogorgia elisabethae specimens collected in the islands of San Andrés and Providencia, Colombian Caribbean, yielded four new diterpenes (1, 3, 5, 7) along with seco-pseudopterosin J (8), and amphilectosins A (9) and B (10). The structures of the new compounds were established through spectral studies as an elisabethatriene analog named elisabethatrienol (1), 10-acetoxy-9-hydroxy- and 9-acetoxy-10-hydroxy-amphilecta-8,10,12,14-tetraenes (isolated as an interconverting mixture) (3), amphilecta-8(13),11,14-triene-9,10-dione (5), and a seco-pseudopterosin 7-O-α-l-fucopyranoside named seco-pseudopterosin K (7). Elisabethatrienol can be regarded as a biosynthetic intermediate leading to erogorgiaene.     

Novel cyclopropyl diketones and 14-membered macrolides from the soil fungus Hamigera avellanea BCC 17816

Two novel cyclopropyl diketones, hamavellone A (1) and B (2), and two new 14-membered nonaketide macrolactones, hamigeromycin A (3) and B (4), together with six known compounds, 89-250904-F1 (radicicol analogue A, 5), pseurotin A (6), emodin (7), ω-hydroxyemodin (8), and emodin bianthrones (9 and 10) were isolated from the soil fungus Hamigera avellanea BCC 17816. The structures of the new compounds were defined by analysis of NMR and MS data. The absolute stereochemistry of 3 was addressed by chemical correlation to 5. Hamavellone B (2) exhibited antimalarial activity with an IC₅₀ of 5.2 μg/mL, whereas it also showed comparable cytotoxicity.     

Antimicrobial sesquiterpenes from the Chinese medicinal plant, Chloranthus angustifolius

Two new eudesmane-type sesquiterpenes, 9α-hydroxycurcolonol (1) and 3α-hydroxy-4-deoxy-5-dehydrocurcolonol (2), along with nine known sesquiterpenes (3–11), were isolated from the roots of Chloranthus angustifolius. The antimicrobial activities of compounds 1–11 were evaluated against five bacteria and six fungal strains. Compounds 6–11 showed potent activities against Candida albicans with MIC values ranging from 4 to 8 μg/mL. The structures of the two new compounds 1 and 2 were established by a detailed analysis of their NMR and mass spectroscopic data.     

New phlegmarane-type, cernuane-type, and quinolizidine alkaloids from two species of Lycopodium

Two new phlegmarane-type alkaloids, cermizines A (1) and B (2), three new quinolizidine alkaloids, cermizine C (3) and senepodines G (4) and H (5), and a new C₁₆N₂ type alkaloid consisting of a quinolizidine and a piperidine ring, cermizine D (6), as well as two new cernuane-type alkaloids, cernuine N-oxide (7) and lycocernuine N-oxide (8), have been isolated together with cernuine (9) and lycocernuine (10) from the club moss Lycopodium cernuum and L. chinense. The relative stereochemistry of 1-4 and 6, and the absolute stereochemistry of 5, 7, and 8 were elucidated by combination of NOESY correlations, modified Mosher's method, chemical transformations, and computational methods. Cermizine D (6) might be a biosynthetic intermediate of cernuane-type alkaloids such as 7-10.