(+)-N-Deoxymilitarinone A, a neuritogenic pyridone alkaloid from the insect pathogenic fungus Paecilomyces farinosus

A new pyridone alkaloid, (+)-N-deoxymilitarinone A (1), was isolated from Paecilomyces farinosus RCEF 0097 along with the related metabolites, militarinone D and militarinone B. The sterol 22E,4R-ergosta-7,22-diene-3beta,5alpha,6beta,9alpha-tetraol was also identified. The structures were established by spectroscopic methods, in particular with the aid of extensive NMR experiments. Compound 1 induced neurite sprouting in PC 12 cells when tested at 33 and 100 microM concentrations. A cytotoxic effect was observed in human neurons (IMR-32) at a concentration of 100 microM.     

Pyridone and tetramic acid alkaloids from the spider pathogenic fungus Torrubiella sp. BCC 2165

Torrubiellones A-D (1-4), new pyridone and tetramic acid alkaloids, were isolated from the spider pathogenic fungus Torrubiella sp. BCC 2165. Torrubiellone A (1) exhibited antimalarial activity with an IC(50) value of 8.1 μM, while it showed very weak cytotoxic activity.     

Cytotoxic pyridone alkaloids from the leaves of Piper aborescens

Bioactivity-guided fractionation of a CHCl3 extract of the leaves of Piper aborescens afforded a new cytotoxic pyridone alkaloid, N-(3-methoxy-4,5-methylenedioxydihydrocinnamoyl)-delta 3-pyridin-2-one [1], as well as three known cytotoxic pyridone alkaloids, N-(3-methoxy-4,5-methylenedioxycinnamoyl)-delta 3-pyridin-2-one [2], piplartine [3], and piplartine dimer A [4].     

Aurantosides G, H, and I: three new tetramic acid glycosides from a Papua New Guinea Theonella swinhoei

Aurantosides G-I (1-3) have been isolated from the lithistid sponge Theonella swinhoei from Papua New Guinea. Their structures were established by spectroscopic and chemical methods. Compounds 1-3 represent new monochloropentaenoyl tetramic acids with mono-, di-, and tri-N-saccharide substituents, respectively. Aurantosides G-I (1-3) failed to show any significant cytotoxicity against the human colon tumor cell line HCT-116.     

Cyclic heptapeptides from the Jamaican sponge Stylissa caribica

Two new cyclic heptapeptides, stylisin 1(1) and stylisin 2 (2), were isolated and characterized from the Jamaican sponge Stylissa caribica, in addition to the cyclic heptapeptide phakellistatin 13 (3) and the known bromopyrrole alkaloids sceptrin (4), stevensine (5), and oroidin (6). The new structures were assigned on the basis of 1D and 2D NMR spectroscopic data, as well as chemical methods for the elucidation of the absolute configuration of amino acids. The peptides and alkaloids have been evaluated for their antimicrobial, antimalarial, anticancer, anti-HIV-1, anti-Mtb, and antiinflammatory activities.     

Biologically active aspidofractinine, rhazinilam, akuammiline, and vincorine alkaloids from Kopsia

Eleven new indole alkaloids, in addition to the previously reported rhazinal (1), and 14 other known alkaloids, were obtained from the Malayan Kopsia singapurensis, viz., kopsiloscines A-F (2-7), 16-epikopsinine (8), kopsilongine- N-oxide (9), 16-epiakuammiline (10), aspidophylline A (11), and vincophylline (12). The structures of these alkaloids were determined using NMR and MS analyses. Rhazinal (1), rhazinilam (17), and rhazinicine (18) showed appreciable cytotoxicity toward drug-sensitive as well as vincristine-resistant KB cells, while kopsiloscines A (2), B (3), and D (5) and aspidophylline A (11) were found to reverse drug-resistance in drug-resistant KB cells.     

Identification of new cactus alkaloids in Backebergia militaris by tandem mass spectrometry

Tandem mass spectrometry, applied to simple extracts of Backebergia militaris, indicated the presence of a number of new alkaloids, including fully aromatic oxygenated isoquinolines, their di- and tetra-hydro analogs, and beta-phenethylamines. These conclusions were supported by separation using radial tlc and comparison with authentic compounds. Traces of seven alkaloids new to this cactus species were identified; four (3,4,8,11) were known previously from other cacti. Three novel cactus alkaloids were identified and confirmed by synthesis as 7,8-dimethoxy-3,4-dihydroisoquinoline (12, dehydrolemaireocereine), 6,7-dimethoxyisoquinoline (13, backebergine), and 7,8-dimethoxyisoquinoline (14, isobackebergine). The last two compounds are the first simple, fully aromatic, isoquinoline alkaloids to be reported from the Cactaceae. The sensitivity of this approach to new alkaloid discovery is emphasized; the entire project consumed only 10 g of dried plant material.     

黄杨宁原料中生物碱的分离与鉴定

目的分离鉴定黄杨宁原料中的生物碱,为黄杨宁及其制剂质量控制提供依据。方法用高效液相色谱法分析并分离纯化黄杨宁中各主要生物碱成分,通过理化方法及光谱分析鉴定化学结构。结果黄杨宁中主要含环维黄杨星D,另外两个次要成分分别为环黄杨碱D和环常绿黄杨碱C。结论经色谱分析、分离和光谱鉴定,确证黄杨宁主要由具有相同骨架结构的同系生物碱组成。环维黄杨星D单体不易由传统的柱色谱或重结晶分离等方法制得。     

Daphniyunnines A-E, alkaloids from Daphniphyllum yunnanense

The first chemical study on the stems and leaves of Daphniphyllum yunnanense led to the isolation of five new alkaloids, daphniyunnines A-E (1-5). Daphniyunnines B-E (2-5) are four unusual C-22 nor-Daphniphyllum alkaloids. The structures of these alkaloids were characterized by spectroscopic methods, especially 2D NMR techniques. A single-crystal X-ray diffraction analysis was used to confirm the structure of 1. Daphniyunnine D (4) showed cytotoxicity against two tumor cell lines, P-388 and A-549, with IC(50) values of 3.0 and 0.6 microM, respectively.     

Three new toxic norditerpenoid alkaloids from the low larkspur Delphinium nuttallianum

Three new N-(methylsuccinimido)anthranoyllycoctonine norditerpenoids, given the names bearline (1), 14-acetylbearline (2), and 16-deacetylgeyerline (3), were isolated from the extract of the low larkspur Delphinium nuttallianum. The structures of the individual alkaloids were determined by (1)H and (13)C NMR spectroscopy and HRMS. These alkaloids are structurally related to the neurotoxic alkaloid methyllycaconitine (4) and may be important in establishing the toxicity of low larkspurs to cattle. A mouse bioassay was used to measure the LD(50) values for two of the new alkaloids (1 and 2), as sufficient quantities of 3 were not available for toxicity testing. A structurally related alkaloid, geyerline (7), was isolated from D. geyeri in sufficient quantities for toxicity testing. The toxicities of 1, 2, and 7 were found to be comparable to that of 4, with calculated LD(50) values in mice of 5.7, 3.3, and 6.2 mg/kg, respectively.     

Ancistroealaines A and B, two new bioactive naphthylisoquinolines, and related naphthoic acids from Ancistrocladus ealaensis

Two new 5,8'-coupled naphthylisoquinoline alkaloids, ancistroealaines A (1) and B (2), eleutherolic acid (3), and two naphthoic acids, ancistronaphthoic acid A (4) and B (5), have been isolated from Ancistrocladus ealaensis. Their structures were determined by spectroscopic, chemical, and chiroptical methods. Ancistroealaine A (1) exhibited activity against Leishmania donovani and Trypanosoma cruzi in vitro.     

Lakshminine,a new rare oxoisoaporphine alkaloid from Sciadotenia toxifera,and structural revisions of telazoline and teladiazoline,two related oxoaporphines from Telitoxicum peruvianum and T. glaziovii

Lakshminine (1), a novel oxoisoaporphine alkaloid possessing a C-6 amine substituent, was isolated from a basic fraction from the woody vines (collected from two bush-ropes) of Sciadotenia toxifera. This compound represents the first documented occurrence of an oxoisoaporphine from any Menispermaceae species other than Menispermum dauricum. The structures of two related aporphine alkaloids, telazoline (3) and teladiazoline (5), were revised on the basis of a comparison of their spectral data with that of lakshminine (1).     

Indole glucoalkaloids from Chimarrhis turbinata and their evaluation as antioxidant agents and acetylcholinesterase inhibitors

As part of our study on bioactive agents from Brazilian rainforest plants, two new glucoalkaloids, 3,4-dehydro-strictosidine (1) and 3,4-dehydro-strictosidinic acid (2), were isolated from Chimarrhis turbinata, along with seven known glucoalkaloids, cordifoline (3), strictosidinic acid (4), strictosidine (5), 5 alpha-carboxystrictosidine (6), turbinatine (7), desoxycordifoline (8), and harman-3-carboxylic acid (9). The structures of the new alkaloids were established on the basis of comprehensive spectral analysis, mainly 1D and 2D NMR experiments, as well as high-resolution HRESIMS. Alkaloid 3 showed strong free-radical scavenging activity against 1,1-diphenyl-2-picrylhydrazyl (DPPH) as well as pronounced antioxidant activity evidenced by redox properties measured by ElCD-HPLC. Additionally, alkaloids 1-9 were submitted to TLC screening for acetylcholinesterase inhibitors. Both 7 and 8 were shown to be moderate acetylcholinesterase inhibitors at a concentration of 0.1 and 1.0 microM, respectively. In an in vitro rat brain assay, 7 showed moderate activity (IC(50) 1.86 microM), compared to the standard compound, galanthamine (IC(50) 0.92 microM).     

Alkaloids from a panamanian poison frog, Dendrobates speciosus: identification of pumiliotoxin-A and allopumiliotoxin class alkaloids, 3,5-disubstituted indolizidines, 5-substituted 8-methylindolizidines, and a 2-methyl-6-nonyl-4-hydroxypiperidine

Dendrobates speciosus is a small red or orange frog that occupies a small geographic range in the highlands of western Panama, where it occurs abundantly in some cloud forest habitats. Gc-ms analysis indicated the presence of at least 30 alkaloids in MeOH skin extracts from population samples at the extreme eastern end of the known geographic range. Eleven alkaloids were isolated by cc in quantities sufficient for 2D-nmr spectral analysis, which in some cases confirmed their identity with alkaloids known from other species and in other cases led to assignment of structures. Pumiliotoxin 251D, pumiliotoxin A [307A], pumiliotoxin B [323A], and allopumiliotoxin 267A were identified as major constituents. N-Oxides of 323A and 267A were also isolated. Indolizidines 195B and 223AB with 3-butyl-5-methyl and 3-butyl-5-propyl substituents, respectively, were identified. The 5-substituents of the 8-methyl-indolizidines 207A and 235B' were assigned as -(CH2)3CH = CH2 and -(CH2)5CH = CH2, respectively; indolizidine 235B' from D. speciosus is, thus, a positional double-bond isomer of indolizidine 235B previously isolated from a closely related poison frog, Dendrobates pumilio. A piperidine 241D was isolated and assigned the structure cis-cis-2-methyl-6-nonyl-4-hydroxypiperidine.     

石松生物碱研究进展

本文综述了自1994年以来天然石松生物碱的研究进展和石衫碱甲的抗乙酰胆酯酶生物活性及它的构效关系研究。按照石松生物碱的分类方法，系统归纳了lycopodine,lycodine,fawcettimine和misceualleous四种类型生物碱的结构特点和内在的相互关系，以及各种类型的新天然化合物。石杉碱甲是由我国科学家首先发现的一个天然的石松生物碱，药理实验证明它是一个高选择性的乙酰胆碱酯酶抑制剂，具有口服生物利用度高、作用时间长、副反应小的特点，优于巳上市的第一代治疗老年痴呆药物E2020，Tacrine，Physostigmine和Galanthamine。已合成的大量的石杉碱甲类似物的药理实验表明，作为AChE抑制剂，石杉碱甲是一个紧凑的结构，现有的结构要素一个都不能少。不过。以天然石杉碱甲为原料合成的席夫碱衍生物和用石杉碱甲的结构片断与Tacrine相结合的类似物研究取得了可喜的进展。     

Sanguinones A and B, blue pyrroloquinoline alkaloids from the fruiting bodies of the mushroom Mycena sanguinolenta

Two previously unknown blue alkaloid pigments, sanguinone A (1) and sanguinone B (2), and one new red indoloquinone alkaloid, sanguinolentaquinone (3), have been isolated from Mycena sanguinolenta fruiting bodies. In addition, decarboxydehydrosanguinone A (4) was identified as an oxidative decarboxylation artifact of 1. The structures of these alkaloids have been established by 2D NMR and ESIMS methods. The absolute configurations of 1 and 2 were determined by comparison of their CD spectra with the CD spectrum of mycenarubin A (5), which we isolated recently from fruiting bodies of the mushroom Mycena rosea. The sanguinones are structurally related not only to the mycenarubins A (5) and B but also to a large number of marine alkaloids such as the discorhabdins.     

Antifungal substances against pathogenic fungi, talaroconvolutins, from talaromyces convolutus

The dichloromethane extract of Talaromyces convolutus cultivated on barley exhibited antifungal activity against Candida albicans. In the course of a search for the active compounds, four new tetramic acid derivatives, talaroconvolutins A (1), B (2), C (3), and D (4), were isolated along with ZG-1494alpha (5), and mitorubrin derivatives. The structures of talaroconvolutins A-D (1-4) were established on the basis of spectroscopic and chemical investigations and chemical correlations. The antifungal activity of the talaroconvolutins against the pathogenic fungi Aspergillus fumigates, Aspergillus niger, C. albicans, and Cryptococcus neoformans was determined.     

Putrescine bisamides from Aglaia gigantea

Phytochemical analysis of the leaves of Aglaia gigantea collected in Vietnam yielded three cinnamoyl putrescine bisamide derivatives, which included the known compound dasyclamide ( 1), as well as two new natural products, gigantamide A ( 2) and grandiamide D ( 3). In this study, the structure of dasyclamide ( 1) was confirmed by X-ray crystallography. The structures of the two new alkaloids, gigantamide A ( 2) and grandiamide D ( 3), were elucidated through extensive 1D and 2D NMR spectroscopy and analysis of their mass spectrometric (ESIMS, HRQTOFMS) data. The absolute configuration of grandiamide D ( 3) was determined via Mosher ester derivatization.     

Antimalarial, cytotoxic, and antifungal alkaloids from Duguetia hadrantha

Bioassay-guided isolation of Duguetia hadrantha yielded two new 4,5-dioxo-1-azaaporphinoids, hadranthine A (1) and hadranthine B (2), together with the known alkaloids imbiline-1 (3), sampangine (4), and 3-methoxysampangine (5), whose structures were determined primarily from 2D-NMR 1H-13C HMBC, and 1H-15N HMBC experiments. This is the first report of the co-occurrence of the copyrine alkaloids 4 and 5, as well as the first report of either copyrine or imbiline type alkaloids from a Duguetia species. Compounds 1, 4, and 5 demonstrated in vitro antimalarial activity against Plasmodium falciparum (W-2 clone), while 2 was inactive. Instead, 2 showed in vitro cytotoxicity to selected human cancer cell lines (IC50 = 3-6 microg/mL against SK-MEL, KB, BT-549, and SK-OV-3), and 4 was also cytotoxic to human malignant melanoma (IC50 = 0.37 microg/mL). Sampangine (4) also inhibited cell aggregation with a MIC value of <0.15 microg/mL, while 3-methoxysampangine (5) was only weakly active.     

New cytotoxic alkaloids from the wood of Vepris punctata from the Madagascar rainforest

Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the wood of Vepris punctata resulted in the isolation of three new furoquinoline alkaloids, 5-methoxymaculine (1), 5,8-dimethoxymaculine (2), and 4,5,6,7,8-pentamethoxyfuroquinoline (3), in addition to the four known alkaloids flindersiamine (4), kokusaginine (5), maculine (6), and skimmianine (7). The structures of the new alkaloids 1-3 were established on the basis of extensive 1D and 2D NMR spectroscopic data interpretation. All the isolated compounds were tested against the A2780 human ovarian cancer cell line, and all seven alkaloids showed weak cytotoxic activity.