New cholinesterase inhibiting bisbenzylisoquinoline alkaloids from Cocculus pendulus

Phytochemical investigation on Cocculus pendulus (J. R. & G. FORST.) resulted in the isolation of two new and three known bisbenzylisoquinoline alkaloids. The structures of the new alkaloids, kurramine-2'-beta-N-oxide (1) and kurramine-2'-alpha-N-oxide (2), were elucidated with the help of spectroscopic techniques. The cholinesterase inhibitory activities of these bisbenzylisoquinoline alkaloids are reported here for the first time.     

New bisbenzylisoquinoline alkaloids from Cocculus laurifolius

Two new bisbenzylisoquinoline alkaloids, alpha, alpha'-dioxo-7'-O-demethylstebisimine (1) and 7'-O-demethylstebisimine (2), along with 14 known alkaloids, were isolated from the roots of Cocculus laurifolius. These alkaloids were characterized mainly by spectroscopic methods.     

Bisbenzylisoquinoline Alkaloids from Nelumbo nucifera

From the embryos of the seeds of Nelumbo nucifera, three bisbenzylisoquinoline alkaloids, nelumboferine and nelumborines A and B, were isolated along with four known compounds, neferine, liensinine, isoliensinine and anisic acid. The structures of the new alkaloids were determined mainly by spectroscopic methods.     

Antiplasmodial activity of three bisbenzylisoquinoline alkaloids from the tuber of Stephania rotunda

Three bisbenzylisoquinoline alkaloids were isolated for the first time from Stephania rotunda tuber. Their structures were elucidated by spectroscopic methods and their antiplasmodial activity was investigated in vitro on chloroquine resistant Plasmodium falciparum strain W2. These alkaloids were identified as 2-norcepharanthine (1), cepharanoline (2) and fangchinoline (3). In vitro, they displayed significant antiplasmodial activity with inhibitory concentration 50 values of 0.3, 0.2 and 0.3 μM.     

Host-guest chemistry of alkaloids

Binding of alkaloids by different hosts (native and modified cyclodextrins, cucurbiturils, calixarenes, and metal complexes of porphyrin and Salphen-type ligands), as well as receptor properties of alkaloid based hosts are reviewed. With alkaloids as guests, the largest binding constants and most significant spectral changes, in particular strong fluorescence enhancements induced by complexation with isoquinoline alkaloids, are observed with cucurbituril hosts. Cyclodextrins are successfully employed for improvement of solubility and for chiral separation of alkaloids of different types. Receptor properties of native and modified cinchona and bisbenzylisoquinoline alkaloids have attracted considerable attention for development of chiral selectors for analysis and separation.     

Nomenclature of benzylisoquinoline and related alkaloids

A classification of the bisbenzylisoquinoline, benzylisoquinoline, and related alkaloids is proposed which is based on the biogenetic characteristics of these alkaloids.All-Union Research Institute of Medicinal Plants, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 25–29, January–February, 1981.     

Stereochemical aspects and 13C NMR spectroscopy of the berbamine class of bisbenzylisoquinoline alkaloids

An analysis of the ¹³C NMR spectra of bisbenzylisoquinoline alkaloids of the berbamine type shows the dependence of spectroscopic properties on preferred conformation.     

Synthetic researches in the field of curare alkaloids XVII. Synthesis of 1-(3′-bromo-4′-methoxybenzyl)-6-methoxy-7-hydroxy-n-methyl-1, 2,3, 4-tetrahydroisoquinoline

1-(3′-Bromo-4′-methoxybenzyl)-6-methoxy-7-hydroxy-N-methyl-1, 2,3, 4-tetrahydroisoquinoline is synthesized. It is an intermediate in preparing bisbenzylisoquinoline alkaloids of the gaiatin and dauritsin type.     

Warifteine and methylwarifteine: 1H and 13C assignments by two‐dimensional NMR spectroscopy

The identity and structures of warifteine and methylwarifteine, two tertiary bisbenzylisoquinoline alkaloids of an unusual type, were elucidated and verified by 2D NMR spectroscopy. Complete ¹H and ¹³C NMR spectral assignments were obtained. Copyright © 2003 John Wiley & Sons, Ltd.     

Inhibitory effect of bisbenzylisoquinoline alkaloids on the quick death of mice treated with BCG/LPS

Three bisbenzylisoqinoline alkaloids, chondocurine (Chon), berbamine (Ber), and cycleanine (Cyc) were tested for their protective effect on the quick death of mice primed with bacillus Calmette Guerin (BCG) and elicited with lipopolysaccharide (LPS). Seven-consecutive treatments with Chon or Cyc at a dose of 10 mg/kg following BCG priming resulted in significant improvement in the survival rate. A single dose of Chon also protected the BCG/LPS-treated mice from death if it was given immediately after, not 4 h after, LPS elicitation. These data show that bisbenzylisoquinoline alkaloids can protect mice from the lethal toxicity induced by the BCG/LPS combination treatment by inhibiting the priming with BCG or the elicitation with LPS.     

Evaluation of fast atom bombardment mass spectrometric and low-energy collisional activation tandem mass spectrometric data for the structural elucidation of bisbenzylisoquinoline alkaloids

The fast atom bombardment (FAB) mass spectra and low-energy collisional activation mass spectra of ions generated under FAB were investigated for twelve bisbenzylisoquinoline (BBI) alkaloids. The relative molecular mass of the free base and diquaternary BBI alkaloids can be obtained from FAB data. However, monoquaternary ammonium salts produce only an [M — X]⁺ ion and the relative molecular mass cannot be determined. For Type A (single ether linkage) BBI alkaloids, fragmentation occurs primarily from benzylic and ether cleavages. Thus, the total number of aromatic substituents (OH, OCH₃ or OCH₂O) can be determined for rings A-B, C-D, E and F. For Type B (two either linkages) BBI alkaloids, fragmentation occurs primarily from double benzylic cleavages. Hence only the total number of aromatic substituents can be determined for the upper half of the Type B BBI alkaloids, i.e. rings A-B and C-D. An unknown alkaloid was examined to illustrate the utility of the fragmentation schemes.     

1H and 13C NMR assignments of two new isomeric bisbenzylisoquinoline alkaloids from Cissampelos sympodialis Eichl. (Menispermaceae)

des‐7′‐O‐methylroraimine (compound 1) and epi‐des‐7′‐O‐methylroraimine (compound 2), two new isomeric bisbenzylisoquinoline alkaloids were isolated and characterized as a mixture from the rhizomes of Cissampelos sympodialis Eichl. The unambiguous structural elucidation of both isomers was performed with the aid of HR‐ESI‐MS, FT‐IR, and NMR techniques including COSY, HMQC, HMBC, and NOESY. Copyright © 2013 John Wiley & Sons, Ltd.     

Determination of vapor pressure curves of warifteine and methylwarifteine by using thermogravimetry

Warifteine and methylwarifteine are bisbenzylisoquinoline alkaloids from Cissampelos sympodialis Eichl., produces a reversible, nonspecific, and noncompetitive antagonism of histamine, anti-allergic therapy, and used in the folk medicine for the treatment of airway respiratory diseases. Thermal techniques are used for several purposes, e.g., for thermal characterization, and measurement of the vapor pressure with objective of the quantitative determination. The objective of this study was to evaluate of the vapor pressure of the curves of warifteine and methylwarifteine by thermogravimetry analysis, how a fast and sensible method for quantitative determination. This method is based on the ratio of the Arrhenius, Langmuir, and Antoine equations for a reference material and the sample under investigation. The results showed these alkaloids follow zero-order kinetics with respect to volatilization. The vapor pressure curves of warifteine and methylwarifteine were plotted for the rates of 10, 15, and 20 °C min⁻¹. The proposed method also possesses the potential.     

Steps towards a practical synthesis of macrocyclic bisbenzylisoquinolines

There are more than 400‐reported bisbenzylisoquinoline alkaloids, many with interesting biological activity, but the reported syntheses are long and low yielding. As a result, there have been no systematic attempts at exploitation of the potential therapeutic applications. The concept of a sulfur ‘stitch’, restricting the conformational freedom of intermediates in the synthesis, will potentially allow analogues of the natural products to be prepared using relatively efficient routes. The synthesis of intermediate sulfur heterocycles is reported, based on 2,8‐dimethylphenoxathiin, leading via 2,8‐bis(bromomethyl)phenoxathiin‐10,10‐dioxide to a synthesis of 3,4,8,9‐tetrahydro‐13‐oxa‐6‐thia‐2,10‐diazapentacene, a key potential intermediate on the route to a variety of macrocyclic bisbenzylisoquinolines.     

Seasonal variation in alkaloid composition and antiproliferative activity of <Emphasis Type="Italic">Stylophorum lasiocarpum</Emphasis> (Oliv.) Fedde

Stylophorum lasiocarpum (Oliv.) Fedde (Papaveraceae) belongs to traditional Chinese medicine herbs but there was minimal information on the content of alkaloids in this plant. Extracts from the aerial part and roots were examined by liquid chromatography with UV and mass spectrometric detection, with nineteen alkaloids identified. Changes in alkaloid content over the entire vegetation period of a one- and two-year old plant were studied. The protoberberine alkaloids, coptisine and stylopine, were found to be the main substances in extracts of the aerial part irrespective of the plant’s age and time of harvest. Variable amounts of protopine, sanguinarine, chelerythrine, chelirubine, macarpine, chelilutine and berberine were also recorded in the aerial part. The roots contained significantly larger quantities of all alkaloids than the aerial part with the levels of most alkaloids varying from May to October, peaking in the middle of the vegetation period. Coptisine was the dominant alkaloid in all samples. The antiproliferative activities of the root extract and of seven individual alkaloids were tested on A375 human malignant melanoma cells. The significant dose-dependent toxicity of the root extract was attributed largely to the quaternary benzo[c]phenanthridine alkaloids, macarpine and sanguinarine.     

Nonaqueous capillary electrophoresis for rapid and sensitive determination of fangchinoline and tetrandrine in radix Stephaniae tetrandrae and its medicinal preparations

A simple, rapid, and sensitive non-aqueous capillary electrophoresis procedure with head-column field-amplified sample stacking concentration for the analysis of fangchinoline and tetrandrine is established. Optimum separation and stacking conditions were obtained when the sample was injected at 8 kV for 50 s after preliminary pressure injection of ethanol (16.9 kPa) for 0.6 s and separated with the buffer containing 50 mM ammonium acetate, 0.5% (v/v) acetic acid, and 50% (v/v) acetonitrile in methanol medium at 24 kV applied voltage. The analytes were detected by UV at 214 nm. The two bisbenzylisoquinoline alkaloids can be separated within 6 min and quantified with high sensitivity. The detection limits were 0.30 ng mL(-1) for fangchinoline and 0.34 ng mL(-1) for tetrandrine, which indicated that the sensitivities were at least 1000-fold enhanced over those reported in the literature as obtained by UV detection. The method was applied to the analysis of fangchinoline and tetrandrine in Radix Stephaniae tetrandrae and its medicinal preparations with good results.     

Detection and identification of loline and its analogues in horse urine

Several kinds of loline-type alkaloids, norloline, loline, N-acetylnorloline, N-acetylloline, N-formylnorloline, N-formylloline and N-methylloline were detected in the urine of race-horses. Furthermore, a new compound of the alkaloids, N-senecioylnorloline, was also found and identified. These compounds were mainly identified by means of gas chromatography-mass spectrometry (GC-MS) and gas chromatography-fourier transform-infrared spectrometry (GC-FT-IR). A certain plant of Gramineae containing four kinds of loline-type alkaloids was found in a bale of hay used for the horse forage. The taxonomic feature of the plant was different from known plants containing loline-type alkaloids. The common fragmentation of loline-type alkaloids under electron ionization was briefly discussed.     

Spectrophotometric method for estimation of alkaloids precipitable with Dragendorff's reagent in plant materials

A rapid, easy, and simple spectrophotometric method was developed for the estimation of total alkaloids precipitated by Dragendorff's reagent (DR) in plant materials. It is based on the formation of yellow bismuth complex in nitric acid medium with thiourea. The yellow-colored complex formed obeys Lambert-Beer's law in the concentration range of 0.06-50 microg/mL with lambdamax at 435 nm. Using this method, the alkaloidal percentage of certain alkaloids (ajamalicine, papaverine, cinchonine, piperine, berberine) and some plant materials containing alkaloids (Berberis aristata, Solanum nigrum, and Piper longum) were determined. The method was compared with other methods. It can be used for routine analysis of commercial samples by industries dealing with herbal drugs for standardization of plant materials containing alkaloids and for alkaloid-containing pharmaceutical products.