Phenolic analogs of the N,C-coupled naphthylisoquinoline alkaloid ancistrocladinium A, from Ancistrocladus cochinchinensis (Ancistrocladaceae), with improved antiprotozoal activities

The first N,8′-coupled naphthylisoquinoline alkaloids with free phenolic OH groups, 4′-O-demethylancistrocladinium A and 6,4′-O-didemethylancistrocladinium A, have been isolated from the leaves and bark of the Vietnamese liana Ancistrocladus cochinchinensis, along with its known, non-phenolic parent compound, ancistrocladinium A, and four C,C-coupled representatives. The structure elucidation was achieved by chemical, spectroscopic, and chiroptical methods. The mono-phenolic alkaloid showed excellent activities in particular against the pathogen causing Chagas’ disease, Trypanosoma cruzi.     

Ancistroheynine B and two further 7,3'-coupled naphthylisoquinoline alkaloids from Ancistrocladus heyneanus Wall

A new axially chiral naphthylisoquinoline alkaloid, ancistroheynine B (7), has been isolated from the leaves of the Indian liana Ancistrocladus heyneanus Wall., along with two known related alkaloids, ancistrocladidine (3) and ancistrotanzanine C (6), which are 7,3'-coupled, too. The structural elucidation was achieved by chemical, spectroscopic, and chiroptical methods. Biological activities of ancistroheynine B against the pathogens of malaria, leishmaniasis, Chagas' disease, and African sleeping sickness were evaluated.     

Extract screening by HPLC coupled to MS-MS,NMR, and CD: a dimeric and three monomeric naphthylisoquinoline alkaloids from Ancistrocladus griffithii

Three new monomeric naphthylisoquinoline alkaloids, ancistrogriffines A, B, and C, and the first dimer of a 7,8'-coupled naphthylisoquinoline, ancistrogriffithine A, have been detected by phytochemical online screening of plant extracts of Ancistrocladus griffithii, using the analytical 'triad' HPLC-MS/MS, HPLC-NMR, and HPLC-CD. Ancistrogriffithine A, as well as ancistrogriffines A and C, were structurally completely assigned (including the absolute configuration) right from the extract, without previous isolation. Furthermore, two related, but known alkaloids, ancistrocladine and hamatine, were identified. Except for ancistrogriffine B, which occurs in trace quantities only, all new alkaloids were then isolated preparatively and the initial assignments were fully confirmed by conventional offline methods. Of particular interest is the constitutionally and configurationally unprecedented structure of ancistrogriffithine A, which is simultaneously the first dimeric naphthylisoquinoline alkaloid from an Asian Ancistrocladus species. Ancistrogriffithine A and ancistrogriffine A are active against Plasmodium falciparum. Furthermore, the latter compound shows good activity against Leishmania donovani. The results demonstrate the ability of modern online methods like HPLC-NMR, -MS/MS, and -CD to serve as powerful tools for the reliable structural elucidation of even complex structures of trace compounds in crude biological matrices.     

Six naphthylisoquinoline alkaloids and a related benzopyranone from a Congolese Ancistrocladus species related to Ancistrocladus congolensis

From the roots of a recently discovered Ancistrocladus taxon, with close affinities to Ancistrocladus congolensis regarding molecular ITS sequence data, six naphthylisoquinoline alkaloids, 5'-O-demethylhamatine (2), 5'-O-demethylhamatinine (3), 6-O-demethylancistroealaine A (4), 6,5'-O,O-didemethylancistroealaine A (5), 5-epi-6-O-methylancistrobertsonine A (6), and 5-epi-4'-O-demethylancistrobertsonine C (7), have been isolated, along with a likewise benzopyranone carboxylic acid, 8. The structural elucidation succeeded by chemical, spectroscopic, and chiroptical methods. Their bioactivities were tested against protozoan parasites causing severe tropical diseases. Furthermore, eight known related alkaloids were identified.     

Indole alkaloids from Aspidosperma rigidum and A. schultesii and their antiparasitic effects

Five oxindole alkaloids, three plumerane-type alkaloids, subtype haplophitine, and one aspidospermatane-type alkaloid, subtype tubotaiwine, were isolated from the medicinal plants Aspidosperma rigidum and A. schultesii. One compound was identified as the transoid conformer of 18-oxo-O-methylaspidoalbine which was not previously described. The antiparasitic activity of all compounds against Trypanosoma cruzi and Leishmania infantum and their non-specific cytotoxicity against mammalian cells were also determined.     

(-)-Amarbellisine, a lycorine-type alkaloid from Amaryllis belladonna L. growing in Egypt

A new lycorine-type alkaloid, named (-)-amarbellisine, was isolated from the bulbs of Egyptian Amaryllis belladonna L. together with the well known alkaloids (-)-lycorine, (-)-pancracine, (+)-vittatine, (+)-11-hydroxyvittatine, and (+)-hippeastrine. The new alkaloid, containing the pyrrolo[de]phenanthridine ring system, was essentially characterised by spectroscopic and optical methods, and proved to be the 2-methoxy-3a,4,5,7,11b,11c-hexahydro-1H-[1,3]dioxolo[4,5-j]pyrrolo[3,2,1-de]phenanthridinol. By using HPTLC technique we also carried out a comparative study of the relative and total alkaloidal content at two different stages of plant growth. Finally, the antimicrobial activity of the isolated alkaloids was assayed.     

Indolomonoterpenic alkaloids from Strychnos icaja roots

In the course of our search for new antiplasmodial alkaloids from Strychnos icaja, we have isolated five alkaloids: three monomers, protostrychnine and genostrychnine, previously described in Strychnos nux-vomica, pseudostrychnine, already found in the leaves of the plant, a new bisindolic alkaloid, named strychnogucine C, and the first naturally occurring trimeric indolomonoterpenic alkaloid: strychnohexamine. This latter trimeric alkaloid presented an antiplasmodial activity against the FCA Plasmodium falciparum line near 1 microM.     

E/Z-Thesinine-O-4'-alpha-rhamnoside, pyrrolizidine conjugates produced by grasses (Poaceae)

Based on direct infusion mass spectrometry we identified a novel alkaloid as a major component of perennial ryegrass (Lolium perenne). Initial mass spectral data suggested it to be a pyrrolizidine conjugate. As this class of alkaloids has not been described before from grasses, we isolated it to elucidate its structure. The isolated alkaloid proved to be a mixture of two stereoisomers. The structures of the two compounds as determined by 1D and 2D NMR spectroscopy, were E-thesinine-O-4'-alpha-rhamnoside (1) and Z-thesinine-O-4'-alpha-rhamnoside (2). These identifications were supported by the characterisation by GC-MS and optical rotation of (+)-isoretronecanol as the necine base released on alkaline hydrolysis of these alkaloids. 1 and 2 together with the aglycone and a hexoside were also detected in tall fescue (Festuca arundinacea). This is the first report of pyrrolizidine alkaloids produced by grasses (Poaceae).     

Dioncophylline E from Dioncophyllum thollonii,the first 7,3'-coupled dioncophyllaceous naphthylisoquinoline alkaloid

The isolation and structural elucidation of dioncophylline E, a novel naphthylisoquinoline alkaloid from the rare West African liana Dioncophyllum thollonii, is described. The alkaloid displays an unusual 7,3'-linkage between the naphthalene and the isoquinoline portions. Due to the resulting medium degree of steric hindrance exerted by the ortho-substituents next to the biaryl axis, the compound undergoes slow rotation about the axis at room temperature and thus is the first such alkaloid that occurs as a mixture of two configurationally semi-stable atropo-diastereomers. Dioncophylline E exhibits good antimalarial activity against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum while its antitrypanosomal activity against Trypanosoma cruzi is weak and that against T. brucei rhodesiense is moderate. Furthermore, four additional naphthylisoquinoline alkaloids previously known from the related plant species Triphyophyllum peltatum, have been identified in D. thollonii.     

Alkaloids from Narcissus angustifolius subsp. transcarpathicus (Amaryllidaceae)

Seven alkaloids have been isolated from fresh bulbs of Narcissus angustifolius subsp. transcarpathicus (Amaryllidaceae). Nangustine, reported here for the first time, is the first 5,11-methanomorphanthridine alkaloid with a C-3/C-4 substitution. The structure and stereochemistry of this new alkaloid, as well as those previously known, have been determined by physical and spectroscopic methods. Spectroscopic data of pancracine have been completed. The in vitro assay activity against the parasitic protozoa Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum was carried out with the compounds nangustine and pancracine.     

New class of steroidal alkaloids from Fritillaria imperialis

Two members of a new class of C-nor-D-homo steroidal alkaloids, impranine (1). and dihydroimpranine (2). along with a new pyridyl-pregnane-type steroidal alkaloid, fetisinine (3). and a known base, korsevine (4). were isolated from the bulbs of Fritillaria imperialis. The structures of the compounds were established on the basis of spectroscopic techniques and some chemical transformations. Compounds 1 and 2 form a new class of steroidal alkaloids, named as "impranane."     

Augustamine type alkaloids from Crinum kirkii

Sixteen more Amaryllidaceae alkaloids have been isolated from bulbs of Crinum kirkii Baker of which noraugustamine and 4a,N-dedihydronoraugustamine are hitherto unknown. Their structures and those of earlier known alkaloids have been established by physical and spectroscopic analysis. Application of 2D NMR techniques was used for complete characterization of the alkaloids as well as of 3-O-acetylsanguinine. 1,2-Diacetyllycorine and 3-O-acetylsanguinine showed activity against Trypanosoma brucci rhodesiense, the parasite associated with sleeping sickness. 3-O-acetylsanguinine also showed some activity against Trypanosoma cruzi.     

Angustilobine and andranginine type indole alkaloids and an uleine-secovallesamine bisindole alkaloid from Alstonia angustiloba

A total of 20 alkaloids were isolated from the leaf and stem-bark extracts of Alstonia angustiloba, of which two are hitherto unknown. One is an alkaloid of the angustilobine type (angustilobine C), while the other is a bisindole alkaloid angustiphylline, derived from the union of uleine and secovallesamine moieties. The structures of these alkaloids were established using NMR and MS analysis. Angustilobine C showed moderate cytotoxicity towards KB cells.     

Furoquinoline alkaloids from Teclea nobilis

Five new furoquinoline alkaloids, namely tecleabine (1), tecleoxine (2), isotecleoxine (3), methylnkolbisine (4) and chlorodesnkolbisine (5) were isolated from the aerial parts of Teclea nobilis, together with seven known furoquinoline derivatives; one acridone alkaloid, and one known flavanone. The structures of the alkaloids 1-5 were established by 1D and 2D NMR spectral data, including COSY, HMQC and HMBC experiments, as well as HRMS.     

Ipangulines and minalobines, chemotaxonomic markers of the infrageneric Ipomoea taxon subgenus Quamoclit, section Mina

A comprehensive GC-MS analysis of 8 Ipomoea species belonging to the subgenus Quamoclit, section Mina revealed that the members of this taxon form combinations of two necine bases with rare necic acids resulting in unique pyrrolizidine alkaloids. The occurrence and diversity of these metabolites show remarkable variations: Some species, especially Ipomoea hederifolia and Ipomoea lobata, are able to synthesize a large number of alkaloids whereas others, especially Ipomoea coccinea and Ipomoea quamoclit, are poor synthesizers with only a few compounds. However, these metabolites are apparently chemotaxonomic markers of this infrageneric taxon in general. They represent either esters of (-)-platynecine (altogether 48 ipangulines and 4 further esters including results of a previous study) or esters of (-)-trachelanthamidine, an additional novel structural type called minalobines (altogether 21 alkaloids). Both types are characterized by section-specific rare necic acids, e.g., ipangulinic/isoipangulinic acid, phenylacetic acid. The alkaloids of Ipomoea cholulensis, I. coccinea, I. hederifolia, Ipomoea neei, and Ipomoea quamoclit were mono and diesters of platynecine. Minalobines turned out to be metabolites of I. lobata (Cerv.) Thell. (syn.: Mina lobata Cerv.) lacking ipangulines. The major alkaloid of this species, minalobine R, has been isolated and identified as 9-O-(threo-2-hydroxy-2-methyl-3-phenylacetoxy-butyryl)-(-)-trachelanthamidine on the basis of spectral data. Apparently only two of the species included in this study, Ipomoea cristulata and Ipomoea sloteri, are able to synthesize both, ipangulines as well as minalobines. Minalobine O could be isolated as a major alkaloid of I. cristulata, its structure has been established as 9-O-(erythro-2-hydroxy-2-methyl-3-tigloyloxy-butyryl)-(-)-trachelanthamidine on the basis of spectral data.     

Ancistrine,ancistine, ancistrocladeine trois alcaloides isoles de L'ancistrocladus ealaensis

Ancistrine, ancistine are 2 new alkaloïds isolated from the roots of Ancistrocladus ealaensis. Their structures were determined on the basis of spectral data. Ancistrocladeine is identical with an alkaloïd isolated earlier from Ancistrocladus tectorius.     

Polyavolinamide,an indolosesquiterpene alkaloid from Polyathia suaveolens

A new indolosesquiterpene alkaloid, polyavolinamide, has been identified in the stem of Polyathia suaveolens accompanied by the three previously isolated indolosesquiterpene alkaloids, polyavolensin, polyavolensinol, polyavolensinone, as well as an unidentified triterpene and an aporhine alkaloids. Polyavolinamide was also the major component of the root bark. Its structure was assigned on the basis of ¹¹H and ¹³C NMR, and mass spectrometry.     

Studies on the Alkaloids of Phlegmariurus fordii (Baker) Ching

Three alkaloids were isolated from the whole plant of Phlegmariurus fordii (Baker) Ching. One of them was identified as known Iycodoline. The other two, named phlcgmariurine A, and phlegmariur!ne B, are new alkaloids. The structure of A, was determined by means of spectral analysis and X-ray diffraction. It was proved to be a new tri-cyclie alkaloid as (Ⅰ). The structure of B, was elucidated as (Ⅱ).     

深裂黄草乌二萜生物碱研究

深裂黄草乌(Aconitum vilmorinianum var.altifidum W. T.Wang)又名西南乌头、紫乌头、藤乌,主要分布于云南东北部、贵州西部和四川西部(泸定、天全)海拔2800m的山地。块根可祛风散寒、除湿止痛,民间也用于解乌头中毒。其化学成分未见报道。本文从深裂黄草乌全草中分离鉴定了3个二萜生物碱,一个为C-19骨架类型,两个为C-20骨架类型。其中一个为新化合物,是C-20骨架类型二萜生物碱,命名为深裂黄草乌碱vilmorinianine(Ⅰ),另两个化合物是denudatine(Ⅱ)和deoxyaconitine(Ⅲ),均首次从该植物中得到。     

Megistolactone, a new alkaloid from Sarcomelicope megistophylla

A new quinolone alkaloid, megistolactone (1) was isolated from the bark of Sarcomelicope megistophylla. Its structure has been elucidated on the basis of MS and NMR data. From a biogenetic point of view, this compound should be considered as an oxidation product of 1,2,3,4-tetra-O-subsituted acridone alkaloids, which are also present in the bark.