Phenanthridine Alkaloids Research Articles

The octadecanoic pathway: signal molecules for the regulation of secondary pathways.

Plant defense against microbial pathogens and herbivores relies heavily on the induction of defense proteins and low molecular weight antibiotics. The signals between perception of the aggression, gene activation, and the subsequent biosynthesis of secondary compounds are assumed to be pentacylic oxylipin derivatives. The rapid, but transient, synthesis of cis-jasmonic acid was demonstrated after insect attack on a food plant and by microbial elicitor addition to plant suspension cultures. This effect is highly specific and not caused by a number of environmental stresses such as light, heavy metals, or cold or heat shock. Elicitation of Eschscholtzia cell cultures also led to a rapid alkalinization of the growth medium prior to jasmonate formation. Inhibition of this alkalinization process by the protein kinase inhibitor staurosporine also inhibited jasmonate formation. The induction of specific enzymes in the benzo[c]phenanthridine alkaloid pathway leading to the antimicrobial sanguinarine was induced to a qualitatively and quantitatively similar extent by fungal elicitor, methyl jasmonate, and its linolenic acid-derived precursor 12-oxophytodienoic acid. It is herein proposed that a second oxylipid cascade may exist in plants starting from linoleic acid via 15,16-dihydro-12-oxophytodienoic acid to 9,10-dihydrojasmonate. Experiments with synthetic trihomojasmonate demonstrated that beta-oxidation is not a prerequisite for biological activity and that 12-oxophytodienoic acid and derivatives are most likely fully active as signal transducers. Octadecanoic acid-derived compounds are essential elements in modulating the synthesis of antibiotic compounds and are thus integral to plant defense.

Anti-HIV Alkaloids fromToddalia asiatica

Abstract Bioassay-directed fractionation of a Toddalia asiatica (Rutaceae) extract concentrated anti-HIV activity into fractions rich in quaternary alkaloids. Nitidine (1), a benzo[c]phenanthridine alkaloid, and magnoflorine (2), an aporphinoid alkaloid, have been isolated and identified from these fractions. In an in vitro XTT-based anti-HIV assay, 1-10 μ/ml nitidine (1) inhibited human lymphoblastoid cell killing by HIV-1.

Catecholamines in plants

Catecholamines (CAs) are neurotransmitters in mammals. They have been found in 44 plant families, but no essential metabolic function has been established for them. They are precursors of benzo[c]phenanthridine alkaloids, which are the active principal ingredients of many medicinal plant extracts. CAs have been implicated to have a possible protective role against insect predators, injuries, and nitrogen detoxification. They have been shown to promote plant tissue growth, somatic embryogenesis from in vitro cultures, and flowering. CAs inhibit indole-3-acetic acid oxidation and enhance ethylene biosynthesis. They have also been shown to enhance synergistically various effects of gibberellins.

Chemical and Bioactive Constituents from Zanthoxylum simulans

Two new benzo[c]phenanthridine alkaloids, 6-methyldihydrochelerythrine [1] and 6-methylnorchelerythrine [2], together with 23 known compounds, were isolated from the root bark of Zanthoxylum simulans. Structures were elucidated by spectral analysis. Among them, the pyranoquinoline alkaloids, zanthosimuline [3], and huajiaosimuline [4], exhibited cytotoxic activity. In addition, compound 4 showed significant antiplatelet aggregation activity and induced terminal differentiation with cultured HL-60 cells.

ChemInform Abstract: A Formal New Access to the Benzo(c)phenanthridine Alkaloids: Synthesis of Nitidine and O‐Methyl Fagaronine Analogues.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Studies on the Chemical Constituents of Xanthoxylum nitidum (ROXB.) D. C. (Fagara nitida ROXB.). II. Examination of the Chemical Constituents by Membrane Filtration: Identification of Magnoflorine, a Water-Soluble Quaternary Aporphine Alkaloid.

A membrane filtration, the rejection effectivity of which mainly depends on the pore size of the membrane used, was applied to examination of the chemical constituents of Xanthoxylum nitidum (ROXB.) D. C. (Fagara nitida ROXB.), Rutaceae. The methanol extracts of the wood and bar were subjected to gradient filtrations. Each filtrate given by the separation was semi-quantitatively analyzed by HPLC. Magnoflorine (9), a phenolic quaternary aporphine alkaloid, was dramatically rejected by the ultrafiltration using a membrane with the pore size of 1000 in spite of its expected permeability through the membrane due to its smaller molecular weight than the pore size of the membrane used. Such clear rejection may be attributable to the phenolic functions in 9 because chelerythrine chloride (4), a quaternacy benzo[c]phenanthridine alkaloid, with a close molecular weight to that of 9, passed through the membrane.

Structure and Synthesis of Phenaglydon, a new Quinolone Derived Phenanthridine Alkaloid fromGlycosmis cyanocarpa

Abstract A novel quinolone derived alkaloid of the phenanthridine type, phenaglydon (2), has been isolated from the lipophilic leaf extract of Glycosmis cyanocarpa (Rutaceae) together with schinifoline (1), a prenylated 2-quinolinone characterized by a diene grouping in the side chain. Both structures have been elucidated on spectroscopic evidence. In the case of phenaglydon the proposed structure has additionally been confirmed by synthesis. The co-occurrence of these alkaloids suggests close biogenetic connections between the two compounds.

Synthesis of some benzo[h]quinoline derivatives

AbstractReaction between 6‐methoxy‐1‐tetralone, methyl propiolate and an ammonia‐saturated methanolic solution led to 5,6‐dihydro‐8‐methoxybenzo[h]quinolin‐2(1H)‐one in good yields. Subsequent aromatization, chlorination, substitution and demethylation enabled us to prepare 2‐amino‐substituted benzo[h]quinoline derivatives. These compounds, which are structurally related to the antitumor benzo[c]phenanthridine alkaloids by deletion of a ring, were tested on cultured murine lymphoblastic leukaemia cells (L1210). Results showed that they are devoid of cytotoxicity.

Absence of mutagenicity of benzo[ c]phenanthridine alkaloids in somatic cells of Drosophila melanogaster: Comparison with 7,12-dimethylbenz[ a]anthracene and chrysene

The wing somatic mutation and recombination test (SMART) of Drosophila melanogaster was used to study the mutagenic potential of three benzo[ c]phenanthridines with antileukemic properties, fagaronine, nitidine and O-methylfagaronine, as compared with that of two structurally related aromatic polycyclic hydrocarbons: 7,12-dimethylbenz[ a]anthracene and chrysene. Although toxic to larvae, the benzo[ c]phenanthridines and chrysene gave negative or inconclusive results while 7,12-dimethylbenz[ a]anthracene was found to be highly mutagenic and recombinogenic as previously reported. These results suggest that the alkoxy groups and the quaternary nitrogen of the benzo[ c]phenanthridines may reduce or eliminate their mutagenicity in spite of their similarity to methylated polycyclic aromatic hydrocarbons.

ChemInform Abstract: A Common and General Access to Berberine and Benzo(c)phenanthridine Alkaloids.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Conformational Studies of Hexahydro‐benzo[c]phenanthridine Alkaloids: Solid and Solution Conformations of Deoxycorynoline

AbstractThe conformation of (±)‐deoxycorynoline (4), which was derived from (±)‐corynoline (1), was investigated by X‐ray crystallographic analysis. The crystal structure of (±)‐4 exists in B/C „anti‐cis”︁ conjunction, half‐chair of ring B and twist‐half‐chair of ring C, and shows the same conformation as that of the parent alkaloid (±)‐1. Conformational analyses of CD spectra in solution suggested that (+)‐4, derived from (+)‐1, has essentially the same conformation as in the crystal state of (±)‐4. The CD spectrum of (+)‐4 shows a slight temp.‐dependence, whereas that of (+)‐1 shows no dependency under the same conditions.

A formal new access to the benzo[c]phenanthridine alkaloids, synthesis of nitidine and o-methyl fagaronine analogues.

Previously unreported 2-aryl-1-naphthylamines were obtained in good yields from 2-aryl-1-tetraloneoximes by using the Semmler-Wolf reaction but omitting the acetic anhydride usually present in the reaction mixture. From these amines, through the thermal cyclization of their corresponding ethyl carbamates, a new access to the benzo[c]phenanthridin-6(5H)-ones was found. Preparation of water-soluble Nitidine and O-Methyl Fagaronine analogues bearing an alkylamino side chain on the C-6 position was achieved from these compounds.

Purification and characterization of dihydrobenzophenanthridine oxidase from elicited Sanguinaria canadensis cell cultures

Upon treatment of Papaveracea cells with fungal elicitors, the biosynthesis of benzo[ c]phenanthridine alkaloids is induced. Dihydrobenzophenanthridine oxidase, which catalyzes a later step in the biogenesis of these alkaloids, is one of the enzymes whose activity is elevated in the process. Here we report the 211-fold purification of the oxidase from elicited Sanguinaria canadensis by a combination of ammonium sulfate fractionation, DEAE-Sephadex, CM-Sephadex, Sephadex G-200, and either phenyl Superose or gel filtration chromatography. The purified enzyme utilized molecular oxygen to oxidize dihydrosanguinarine to sanguinarine with concomitant formation of hydrogen peroxide. A pH optimum of 7.0, V max of 27 nkat/mg protein, and apparent K m of 6.0 μ m for dihydrosanguinarine were determined. Dihydrochelerythrine was also found to be a substrate for the purified enzyme, displaying an apparent K m of 10 μ m. However, neither dihydronorsanguinarine nor the indole alkaloid ajmalicine was oxidized, indicating that the enzyme has some substrate specificity. Apparent molecular weight estimates by sodium dodecyl sulfate-polyacryl-amide gel electrophoresis revealed that the most purified enzyme preparation obtained contained a major component of 77 kDa and two minor components between 59 and 67 kDa that can be associated with oxidase activity. Purified enzyme preparations possessed activity that was inhibited by sodium diethyldithiocarbamate, sodium azide, potassium cyanide, 1,4- dl-dithiothreitol, and mercaptoethanol.

Studies on the Chemical Constituents of Rutaceous Plants. Part LXXIII. Total Synthesis of Chelerythrine, a Benzo(c)phenanthridine Alkaloid.

By taking advantage of our novel synthetic methods involving CsF-mediated Claisen rearrangement of an aryl propargyl ether to a 2-methylbenzolfuran and oxidative cleavage of the furan ring to a salicylaldehyde, total synthesis of chelerythrine, a benzo[c]phenanthridine alkaloid, was accomplished via the common intermediate (5) prepared through the two routes shown in Chart 3.

A common and general access to berberine and benzo [c] phenanthridine alkaloids

The S RN1 reactions between o-iodobenzamides and the enolate anion from 2-acetyl homoveratric acid lead to key tricyclic compounds which are easily converted to either berberine or benzo [c] phenanthridine ring systems providing thus a high-yielding and versatile access to both classes of alkaloids.

Total synthesis of N-nornitidine

The benzo[c]phenanthridine alkaloid, N-nornitidine has been synthesized employing a benzyne-vinyl isocyanate cycloaddition as the key transformation.

An Nmr Study of Four Benzophenanthridine Alkaloids

A new dihydrobenzo[c]phenanthridine alkaloid, 12-methoxydihydrochelerythrine {1}, has been isolated from a lipophilic extract of the leaves of Bocconia integrifolia together with three known compounds, dihydrochelerythrine {2}, dihydrosanguinarine {3}, and dihydrochelirubine {4}. The structure of 1 was established by analysis of its spectral data (ir, uv, eims, 1 H- and 13 C-nmr). Extensive 1 H-, 13 C-, and nOe 1D and 2D nmr experiments allowed 1 H and 13 C assignments for 1-4. This is the first report of 13 C-nmr assignments for compounds 2-4

Chemical Transformation of Protoberberines. XVII. Biomimetic Introduction of an Oxy Functionality at the C-10 Position in the Benzo(c)phenanthridine Skeleton: Synthesis of 2,3,7,8,10-Pentaoxygenated Benzo(c)phenanthridine Alkaloids, Chelilutine and Sanguilutine.

An efficient and biomimetic introduction of an oxy functionality at the C-10 position in the benzo[c]phenanthridine skeleton was developed by regioselective oxygenation with salcomine-oxygen. This biomimetic procedure was successfully applied to a synthesis of 2, 3, 7, 8, 10-pentaoxygenated benzo[c]phenanthridine alkaloids, chelilutine (8) and sanguilutine (18), from the corresponding 2, 3, 7, 8-tetraoxygenated benzo[c]phenanthridines.

ミカン科植物成分の研究(第66報)沖縄産サルカケミカン, Toddalia asiatica(L.)LAM.(T.aculeata PERS.), の成分 その1 根皮の成分

Chemical constituents of the root bark of Toddalia asiatica (L.) Lam. (T. aculeata Pers.), Rutaceae, were examined. In addition to twelve known coumarins [toddaculin (2), coumurrayin (5), toddanone (6), 8-(3,3-dimethylallyl)-6,7-dimethoxycoumarin (7), isopimpinellin (8), 6-(3-chloro-2-hydroxy-3-methylbutyl)-5,7-dimethoxycoumarin (9), 6-formyllimettin (10), 5,7,8-trimethoxycoumarin (12), toddasin (13), (+)-toddanol (14), 6-(2-hydroxy-3-methoxy-3-methylbutyl)-5,7-dimethoxycoumarin (18), and toddalolactone (21)] five new coumarins [toddalenol (17), toddalosin (19), 5-methoxysuberenon (23), toddalenone (24), and 8-formyllimettin (25)] were isolated. Furthermore seven known benzo[c]phenanthridine alkaloids [des-N-methylchelerythrine (4), oxychelerythrine (15), arnottianamide (16), oxyavicine (22), avicine (30), chelerythrine (31), and chelerythrine-psi-cyanide (34)] and four known quinoline alkaloids [N-methylflindersine (11), 4-methoxy-1-methyl-2-quinolone (20), skimmianine (35), integriquinolone (36)], one known triterpenoid [beta-amyrin (3)], and four unknown components [unknown I-IV (26)-(29)] were isolated.

Ailanthoidine, a novel benzo(C)phenanthridine alkaloid with a cyanopyridine pendant, from a Xanthoxylum species.

The structure of ailanthoidine isolated from the bark of Xanthoxylum ailanthoides Sieb. et Zucc. has been deduced as 1 on the basis of its spectral data including 2-D NMR spectroscopy and an X-ray analysis of 7B.