Gas chromatographic-mass spectral characteristics of aporphine and tetrahydroprotoberberine alkaloids

The gas chromatographic (GC) and mass spectrometric (MS) properties of the silyl derivatives of aporphine and tetrahydroprotoberberine alkaloids are described. Selected representatives of these chemical classes of pharmacologically active bases were chromatographed on polar (OV-17) and nonpolar (OV-1) columns as their trimethylsilyl derivatives. The aporphines were eluted before the tetrahydroprotoberberines on both the polar and nonpolar columns. Simultaneous resolution of mixtures of aporphines and tetrahydroprotoberberines was readily achieved on the OV-1 column. An SE-30 column, used for combined GC-MS analysis, gave a similar resolution of these alkaloids. The mass spectra observed for the silylated 1,2,9,10-substituted aporphines were similar to those of underivatized aporphines, while the mass spectra of the silylated 1,2,10,11-substituted aporphines differed markedly from the spectra of the underivatized alkaloids. Although the mass spectra of the silylated derivatives of the 2,3,9,10- and 2,3,10,11-substituted tetrahydroprotoberberines were identical, these isomeric derivatives were separated by gas chromatography.     

Alkaloids as inhibitors of photophosphorylation in spinach chloroplasts

A group of 12 alkaloids were tested as inhibitors of photophosphorylation in spinach chloroplasts. Ajmaline, a dihydroindole alkaloid, was found to be the strongest inhibitor of both cyclic and non-cyclic photophosphorylation. Low concentrations of ajmaline also inhibited the dark and light ATPases, and the coupled electron flow from water to ferricyanide, measured either as ferrocyanide formed or as oxygen evolved, but not the uncoupled electron transport or the pH rise of illuminated unbuffered suspensions of chloroplasts. Higher concentrations of ajmaline stimulated, instead of inhibiting, photosynthetic electron transport or oxygen evolution and decreased the pH rise, thus behaving as an uncoupler, such as ammonia.Photophosphorylation was partially inhibited by 100 μM dihydrosanguinarine, 100 μM dihydrochelerythrine (benzophenanthridine alkaloids); 500 μM O,O'-dimethylmagnoflorine, 500 μM N-methylcorydine (aporphine alkaloids) and 1 mM julocrotine. They also inhibited coupled oxygen evolution and only partially (dihydrosanguinarine and dihydrochelerythrine) or not at all (the other alkaloids) uncoupled oxygen evolution.Spegazzinine (dihydroindole alkaloid), magnoflorine, N-methylisocorydine, coryneine (aporphine alkaloids), candicine and ribalinium chloride were without effect on photophosphorylation at 500 μM.     

Studies on the Alkaloids of Stephania yunnanensis

Ten known alkaloids, sinoacutine (Ⅰ), 1-tetrahydropalmatine (Ⅱ), d-stepharine (Ⅲ), 1- stepholidine (Ⅳ), 1-corydalmine (Ⅴ), stephanine (Ⅵ), palmatine (Ⅶ), dehydrocorydalmine (Ⅷ), stepharanine (Ⅸ) and roemerine (Ⅹ) were isolated from the roots of Stephamia yunnanensis H. S. Lo. Their structures were determined from spectral data and chemical evidence.     

Alkaloids of turkish papaver tauricola

The major alkaloids of Papaver tauricola collected in three different parts of Anatolia have proved to be of the rhoeadine type. The three collections possessed different major alkaloids and the existence of chemical strains containing rhoeadine-type alkaloids, is indicated. In addition to the rhoeadine-type alkaloids (rhoeagenine, rhoeadine, oreogenine, oreodine, glaucamine, glaudine and epiglaudine), tetrahydroprotoberberine-(sinactine, scoulerine) and isopavine- (amurensinine) type alkaloids have been isolated as minor products. These findings contrast with the previous literature in which 1-benzyltetrahydroisoquinoline- and proaporphine types were reported to be the major alkaloids.     

Indole alkaloids from the leaves of Philippine Alstonia scholaris

The first seco-uleine alkaloids, manilamine (1) (18-hydroxy-19,20-dehydro-7,21-seco-uleine) and N4-methyl angustilobine B (2), were isolated from the (pH 5) alkaloid extract of Philippine Alstonia scholaris leaves together with the known indole alkaloids 19,20-(E)-vallesamine (3), angustilobine B N4-oxide (4), 20(S)-tubotaiwine (5), and 6,7-seco-angustilobine B (6). The structure of the alkaloids was established from MS and NMR experiments.     

Two New Diterpenoid Alkaloids from Spiraea japonica L.f.var. Fortunei (Planchon) Rehd.

Two new hetisine-type C20-diterpenoid alkaloids named spiraqine (1) and 6-hydroxylspiraqine (2), and four known alkaloids, namely spiredine (3), spiradine A (4), spiradine B (5), and spirasine Ⅴ/Ⅵ (6),were isolated from Spiraea japonica L. f. var. fortunei (Planchon) Rehd. The structures of the alkaloids were elucidated using nuclear magnetic resonance analysis (1H-NMR, 13C-NMR, DEPT, HMQC, and HMBC) and mass spectrometry data.     

Nitensidine A,a guanidine alkaloid from Pterogyne nitens,is a novel substrate for human ABC transporter ABCB1

The Pterogyne nitens (Fabaceae) tree, native to South America, has been found to produce guanidine alkaloids as well as bioactive flavonols such as kaempferol, quercetin, and rutin. In the present study, we examined the possibility of interaction between human ATP-binding cassette (ABC) transporter ABCB1 and four guanidine alkaloids isolated from P. nitens (i.e., galegine, nitensidine A, pterogynidine, and pterogynine) using human T cell lymphoblast-like leukemia cell line CCRF-CEM and its multi-drug resistant (MDR) counterpart CEM/ADR5000. In XTT assays, CEM/ADR5000 cells were resistant to the four guanidine alkaloids compared to CCRF-CEM cells, although the four guanidine alkaloids exhibited some level of cytotoxicity against both CCRF-CEM and CEM/ADR5000 cells. In ATPase assays, three of the four guanidine alkaloids were found to stimulate the ATPase activity of ABCB1. Notably, nitensidine A was clearly found to stimulate the ATPase activity of ABCB1 as strongly as the control drug, verapamil. Furthermore, the cytotoxic effect of nitensidine A on CEM/ADR5000 cells was synergistically enhanced by verapamil. Nitensidine A inhibited the extrusion of calcein by ABCB1. In the present study, the possibility of interaction between ABCB1 and two synthetic nitensidine A analogs (nitensidine AT and AU) were examined to gain insight into the mechanism by which nitensidine A stimulates the ATPase activity of ABCB1. The ABCB1-dependent ATPase activity stimulated by nitensidine A was greatly reduced by substituting sulfur (S) or oxygen (O) for the imino nitrogen atom (N) in nitensidine A. Molecular docking studies on human ABCB1 showed that, guanidine alkaloids from P. nitens dock to the same binding pocket as verapamil. Nitensidine A and its analogs exhibit similar binding energies to verapamil. Taken together, this research clearly indicates that nitensidine A is a novel substrate for ABCB1. The present results also suggest that the number, binding site, and polymerization degree of the isoprenyl moiety in the guanidine alkaloids and the imino nitrogen atom cooperatively contribute to their stimulation of ABCB1's ATPase activity.     

丽江乌头中的一个新二萜生物碱

从丽江乌头根中分离、鉴定了三个二萜生物碱成分,其中碱Ⅰ、碱Ⅱ分别为已知成分阿克诺辛(aconosine)和嘟拉碱(dolaconine);碱Ⅲ为一新的C_(18)-型二萜生物碱,从MS、IR、~1H NMR、~(13)C NMR等光谱数据推定了其结构,并命名为丽日碱甲(liconosine A)。     

Oviposition-stimulatory activity of phenanthroindolizidine alkaloids of host-plant origin to a danaid butterfly, Ideopsis similis

Oviposition response of Ideopsis similis (L.) (Lepidoptera: Danaidae) was examined for 12 phenanthroindolizidine alkaloids present in its host plant, Tylophora tanakae (Maxim.) (Asclepiadaceae). At least five alkaloids, i.e. (+)‐isotylocrebrine (3,4,6,7‐tetramethoxyphenanthroindolizidine; l ), (+)‐3‐demethyliso‐ tylocrebrine ( 3 ), (+)‐isotylocrebrine N‐oxide ( 5 ), (+)‐6‐demethyltylocrebrine ( 8 ) and (–)‐7‐demethyltylophorine ( 10 ), were found to individually stimulate oviposition by females. Of these, compounds 1, 3 and 10 were regarded as key components most responsible for host recognition or preference. However, female egg‐laying was much higher in response to a mixture of the five alkaloids. In two‐choice bioassays, more eggs were deposited on samples comprising the five alkaloids than on samples consisting of a single alkaloid. This suggests strongly that host selection by the butterfly is mediated by the synergistic action of several phenanthroindolizidine alkaloids present in the host plant.     

β-Phenethylamine,tetrahydroisoquinoline and indole Alkaloids of Desmodium tiliaefolium

Ten alkaloids (I-X), five β-phenethylamines, two tetrahydroisoquinolines, and three indole-3-alkylamines, have been isolated from Desmodium tiliaefolium. Chemical transformations, spectral (UV,IR, NMR, MS) evidence, and in most cases comparison with reference materials established their identity as tyramine (I), hordenine (II), 3,4-dimethoxy-β-phenethylamine (III), N,N- dimethyl-3,4-dimethoxyphenethylamine (IV), N-methyl-3,4-dimethoxy-β-hydroxyphenethylamine (V), salsoline (V1), salsolidine (VII), tryptamine (VIII), abrine (IX), and hypahorine (X). Alkaloid (V) is a new naturally occurring compound, while no tetrahydroisoquinoline alkaloid has been encountered before in this genus. This is the first time that three different types of alkaloids have been reported in a single legume species. In addition to the above alkaloids, four quaternary β-phenethylamines and tetrahydroisoquinoline alkaloids have been detected, and choline and betaine have been isolated from the water-soluble alkaloid fraction of the roots.     

New steroidal alkaloids from the bulbs of Fritillaria puqiensis

Six new steroidal alkaloids, namely puqienines C-E (1-3), puqiedine (4), 3alpha-puqiedin-7-ol (5), and puqietinedione (6), along with two known steroidal alkaloids puqiedinone (7) and peimisine (8), were isolated from the bulbs of Fritillaria puqiensis G.D. Yu et G.Y. Chen (Liliaceae). Their structures were elucidated on the basis of spectroscopic analysis, including 1D and 2D NMR experiments. Among these alkaloids, 1-3 had a veratramine-type skeleton, 4, 5, 7 a cevanine-type skeleton, 6 a secosolanidine-type skeleton, and 8 a jervine-type skeleton. The existence of multiple types of steroidal skeletons, especially of relatively large amount of veratramine-type alkaloids in one species is rare in the genus Fritillaria, and the results might be of chemotaxonomic significance for this species.     

Two New Diterpenoid Alkaloids from Spiraea japonica L. f. var.fortunei （Planchon） Rehd.

Two new hetisine-type C20-diterpenoid alkaloids named spiraqine (1) and 6-hydroxylspiraqine (2), and four known alkaloids, namely spiredine (3), spiradine A (4), spiradine B (5), and spirasine V/VI (6),were isolated from Spiraea japonica L. f. var.fortunei (Planchon) Rehd. The structures of the alkaloids were elucidated using nuclear magnetic resonance analysis (1H-NMR, ^13C-NMR, DEPT, HMQC, and HMBC) and mass spectrometry data.     

In vitro anticholinesterase activity of various alkaloids

In the current study, a number of alkaloids including retamine, cytisine, and sparteine (quinolizidine-type), yohimbine and vincamine (indole-type), scopolamine and atropine (tropane-type), colchicine (tropolone-type), allantoin (imidazolidine-type), trigonelline (pyridine-type) as well as octopamine, synephrine, and capsaicin (exocyclic amine-type) were tested in vitro for their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) at 1 mg/ml concentration by the Ellman method using an ELISA microplate reader. Among the alkaloids tested, only capsaicin exerted a remarkable inhibitory effect towards both AChE and BChE [(62.7 +/- 0.79)% and (75.3 +/- 0.98)%, respectively]. While the rest of the alkaloids did not show any significant inhibition against AChE, three of the alkaloids, namely retamine, sparteine, and yohimbine, exerted a noteworthy anti-BChE effect as compared to galanthamine, the reference drug.     

滇南草乌的化学成分研究（Ⅱ）

接前文此报告推定了从滇南草乌中分到的碱9—12的结构分别为8-去乙酰黄草乌碱甲(9),talatizidine(10),condelphine(11)和滇乌碱(12)。碱9为首次报告的新化合物,命名为南乌碱乙(austroconitine B)(9)。     

The alkaloids and other constituents from the root and stem of Aristolochia elegans

Two new aristolactams, aristolactam E (1) and aristolactam-AIIIa-6-O-beta-D-glucoside (2), three novel benzoyl benzyltetrahydroisoquinoline ether N-oxide alkaloids, aristoquinoline A (3), aristoquinoline B (4), and aristoquinoline C (5), and a new biphenyl ether, aristogin F (6), together with 62 known compounds have been isolated from the root and stem of Aristolochia elegans Mast. The structures of the new natural products were established on the basis of spectral evidence. Some of the isolated compounds were examined for their antioxidative and antityrosinase activities. Occurrence of the isoquinolones, biphenyl ethers, and benzoyl benzyltetrahydroisoquinoline ether alkaloids in the same plant indicated the definite possibility of these metabolites as biotransformation intermediates of bisbenzyltetrahydroisoquinoline alkaloids. This can be useful to solve the catabolic process of bisbenzyltetrahydroisoquinoline alkaloids.     

DNA-binding affinities and sequence specificities of protoberberine alkaloids and their demethylated derivatives: a comparative study

Berberrubine (1a), jatrorubine (2a), and palmatrubine (3a) have been chemically prepared by partial demethylation of berberine (1), jatrorrhizine (2), and palmatine (3), respectively. Their interactions with calf thymus (CT) DNA, poly(dA-dT)poly(dA-dT), poly(dG-dC)poly(dG-dC), and eight AT-rich 12-mer double-stranded DNAs have been investigated by means of competitive ethidium bromide (EB) displacement experiments. The results showed that DNA-binding affinities of these protoberberine alkaloids have been significantly improved by partial demethylation, and that all of these alkaloids have the preferable binding affinities with AT-rich DNA. Especially, the sequence specificities of DNA-binding of demethylated derivatives 1a, 2a, and 3a had changed to a certain extent when compared with the parent alkaloids 1, 2, and 3, respectively. The binding mode of these alkaloids was further confirmed by UV spectroscopic titration experiments. All the compounds bind to double-stranded DNA most probably via an intercalating mode.     

Studies on the Alkaloids of Cyclea hainanensis Merr

Seven alkaloids have been isolated from the over ground parts of Cyclea hainanensis Merr (Menispermaceae) grown in Hainan is]and. Six of them are identified to be (-) curine (Ⅰ), (+)-4"-O-methylcurine (Ⅱ), hayatine (Ⅲ), d-isochondodendrine (Ⅳ), α-cyclanoline (Ⅴ), and a new quaternary alkaloid named α-hainanine (Ⅵ) respectively. Alkaloid (Ⅶ) is being identified. Dimethiodide and Dimethochloride derivatives of alkaloids (Ⅰ)—(Ⅲ) show neuromuscular blocking activity, but disochondodendrine hydrochloride possesses distinct analgesia.     

Induction of apoptosis by carbazole alkaloids isolated from Murraya koenigii.

In the current study, we isolated 10 carbazole alkaloids from the plant species Murraya koenigii (Rutaceae), and examined their effects on the growth of the human leukemia cell line HL-60. Three carbazole alkaloids, mahanine (6), pyrayafoline-D (7) and murrafoline-I (9), showed significant cytotoxicity against HL-60 cells. Fluorescence microscopy with Hoechst 33342 staining revealed that the percentage of apoptotic cells with fragmented nuclei and condensed chromatin was increased in a time-dependent manner after treatment with each alkaloid. Interestingly, each carbazole alkaloid induced the loss of mitochondrial membrane potential. In addition, both caspase-9 and caspase-3 were also time-dependently activated upon treatment with the alkaloids. Caspase-9 and caspase-3 inhibitors suppressed apoptosis induced by these alkaloids. The results suggest that these three alkaloids induced apoptosis in HL-60 cells through activation of the caspase-9/caspase-3 pathway, through mitochondrial dysfunction.     

Efficient synthesis of solasodine, O-acetylsolasodine, and soladulcidine as anticancer steroidal alkaloids

An efficient synthesis of the steroidal alkaloids solasodine (1), O-acetylsolasodine (2), and soladulcidine (3) starting from easily available diosgenin and tigogenin in five or six steps (overall yield 25, 24, and 28%, resp.) is described. Moreover, our synthetic route provides a selective modification at C(3) of 1 and related compounds in order to carry out lead optimization on these natural antitumor steroidal alkaloids.     

单面针的生物碱研究

自芸香科(Rutaceae)花椒属植物单面针(Zanthoxylum nitidum var. fastuosum How ex Huang)的根皮中分得五种已知生物碱:乙氧基白屈菜红碱(ethoxychelerythrine)(Ⅰ);氯化光花椒碱(nitidine chloride)(Ⅱ);去甲基白屈菜红碱(des-N-methychelerythrine)(Ⅲ);α—别隐品碱(α-allocryptopine)(Ⅳ);鹅掌揪宁(liriodenine)(Ⅴ).