Hypepontine,a new quaternary alkaloid with antimicrobial properties

Abstract

New isoquinoline alkaloid hypepontine (1) together with a five known compounds, were identified in Hypecoum ponticum Velen, the partial synonym of Hypecoum procumbens L. The structure of the new substance was elucidated based on spectroscopic evidence. The tertiary and quaternary alkaloid mixtures as well as the isolated alkaloids were evaluated for their antibacterial and antifungal activity. The result revealed that the crude alkaloid mixture containing quaternary isoquinoline alkaloids showed potent antifungal and antibacterial activity.     

Disproof of the Overall Enzymatic Biosynthesis of Vindoline from Tryptamine and Secologanin by Cell-Free Extracts from the Leaves of Catharanthus roseus (L.) G. DON

A cell-free extract, which was isolated from the leaves of mature Catharanthus roseus plants by a previously published procedure, does not convert a mixture of secologanin and radiolabelled tryptamine to vindoline, as was recently claimed. The radioactivity in the purified alkaloid extract determined by earlier workers is certainly due to ‘impurities’ in the presumed ‘vindoline’. This was shown by extensive purification of the alkaloid extract (which contained added unlabelled vindoline as a carrier) followed by chemical conversion of vindoline to two derivatives and subsequent purification, ultimately giving unlabelled deacetylvindoline.     

Alkaloids of Siberia and altai flora. 17.* Synthesis of <Emphasis Type="Italic">N</Emphasis>-containing derivatives of the diterpene alkaloid lappaconitine

Nitro-derivatives of lappaconitine were synthesized for the first time by nitration of the alkaloid and its 5′-bromo-derivative using a trifluoroacetic acid and potassium nitrate nitrating mixture. Reduction of the nitro-derivatives by Sn(II) chloride in HCl produced the corresponding amino-derivatives of N-deacetyllappaconitine.     

Alkaloids ofHypecoum erectum,the structure of hyperectine

The structure of a new spirobenzylisoquinoline alkaloid fromHypecoum erectum L. has been established by spectral methods and also by the x-ray structural analysis of its methiodide. It has been shown that the alkaloid, which has been called hyperectine, has a pentacyclic structure in which the tetrahydroisoquinoline fragment has the sofa conformation and the indan fragment the envelope conformation. The natural alkaloid is a mixture of the enantiomeric C-8(S), C-16(R), and C-8(R), C-16(S) forms.All-Union Scientific-Research Institute of Medicinal Plants, Moscow. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 628–635, September–October, 1984.     

Functional polymers. III. Asymmetric Michael reactions catalyzed by cinchona alkaloid–acrylonitrile copolymers

The enantio-differentiating abilities of cinchona alkaloid–acrylonitrile copolymers (AN–CA) in the Michael reactions were studied. The reaction of methyl indan-1-one-2-carboxylate (I) with methyl vinyl ketone in toluene at room temperature yielded product (II) in 24–42% optical yield, depending on the type and frequency of the alkaloid units on the polymeric skeleton. The catalysts were recovered from the reaction mixture by filtration and with retention of their stereoselectivities. Modification of the amino or hydroxyl group of the alkaloid moiety greatly reduced the reaction rate and optical yield. The asymmetric reactions of other donors (III–VII) with methyl vinyl ketone were also studied.     

Synthesis of Benzazepine Analogues of Noscapine

The synthesis of benzazepine analogues of the opium alkaloid noscapine ( 1 ) is described. The benzazepines 2 and 3 were prepared starting from nornarceine ethyl ester ( 4 ; readily available from 1 ) in several steps. X-Ray analysis of compound 2 revealed that it is not a diastereosisomer mixture but a racemate of the threo-form and thus has the same configuration as 1 .     

Synthese des Pyrrolizidin-Alkaloides (±)-Trachelanthamidin

Synthesis of the Pyrrolizidine Alkaloid (±)-Trachelanthamidine The important intermediate in the synthesis of the title compound 8 is the diastereoisomer mixture of ethyl 2-[2-(1,3 dioxolan-2-yl)ethyl]-5-oxopyrrolidine-3-carboxylate ( 3a/3b ) which was prepared from nitromethane, acrylaldehyde, and diethyl fumarate (Scheme). Its reduction (NaBH₄, t-BuOH, MeOH) gave exclusively the trans-alcohol 4a , which was converted to the protected pyrrolidine derivative 6 . The deprotection and reduction of 6 gave the pyrrolizidine alkaloid 8 , characterized as its hydrochloride.     

The chemistry of 2H-3,1-benzoxazine-2,4(1H)-dione (isatoic anhydride). 12. Synthesis of araliopsine and isoplatydesmine

N-Methylisatoic anhydride reacts with the lithium enolate derived from 3,3-dimethyloxiranepropanoic acid ethyl ester (7) to initially produce the acyclic β-ketoester 8 . Under neutral conditions, 8 spontaneously cyclizes to the alkaloid araliopsine ( 1a ). In the presence of acid, 8 cyclizes to a mixture of 1a and its leanear isomer isoplatydesmine (2a).     

4(1H)-Quinolinone Alkaloids. An Efficient Synthesis of Graveoline by Palladium-Catalysed Reductive N-Heterocyclisation

An efficient synthesis of the 4H-quinolone alkaloid graveoline has been achieved by a route featuring an Pd(II)-catalysed reductive N-hetero-cyclisation [CO(3 MPa), Pd(TMB)₂, TMPhen, 170°C, 3h] of 2′-nitrochalcone as a key step.     

Piperaceae Alkaloids: Part III. Synthesis of N-isobutyl-11-(3,4-methylenedioxyphenyl)-undeca-2,4,6-trans,trans, trans-trienoic amide and N-isobutyl-11-(3,4-methylenedioxyphenyl)-undeca-2,8,10-trans,trans, trans-trienoic amide (piperstachine)

N-Isobutyl-11-(3, 4-methylenedioxyphenyl)-undeca-2,4,6-trans, trans, trans-trienoic amide (II) and N-isobutyl-11-(3,4-methylenedioxyphenyl)-undeca-2,8,10-trans, trans, trans-trienoic amide (III), two of the three possible structures of the alkaloid piperstachine, have been synthesized. Compound (III) has been found to be identical with piperstachine. The ¹H- and ¹³C-NMR. spectra of the compound (II) are discussed.     

Neuartige Alkaloide aus dem Giftdrüsensekret sozialparasitischer Ameisen (Myrmicinae: Leptothoracini)

Novel Alkaloids from the Poison Glands of Ants Leptothoracini Novel pyrrolidine alkaloids were isolated from the poison glands of ants Leptothoracini(Myrmicinae) and identified as a mixture of N-alkylated 3-methylpyrrolidines. The females of these species produce male-attracting pheromones in their poison glands. The basic compounds in the secretions were found to be active. The major alkaloid, 3-methyl-1-(3-methylbutyl)pyrrolidine ( 5 ), is present in only ng quantities per gland.     

Applying Aluminum Oxide Column Chromatography Purify Extracts of Cathuranthus Roseus and Simultaneous Determination of the Indole Alkaloids by HPLC

Indole alkaloid of Cathuranthus roseus was purified by applying aluminum oxide column chromatography and an HPLC method was established to determine it. Applying aluminum oxide column chromatography produced a high purified monomer of alkaloids; the extracts of indole alkaloid were then loaded on the neutral aluminum oxide column chromatography and washed with an organic solvent (a mixture of chloroform, ether, and petroleum ether). Effect of purification was the best when the proportion of chloroform, ether, and petroleum ether was 10:10:1. To determine the content of vindoline, vinblastine, and cathuranthine exactly, the mobile phase of HPLC was water (containing 0.005 mol·L^?1 ammonium hydrogen phosphate), methanol (containing 0.67% triethylamine), and acetonitrile, the proportion of each was nonlinear.     

Intramolecular Carbenoid Reactions of Pyrrole Derivatives. A Total Synthesis of (±)-Ipalbidine

A new method for alkaloid synthesis is described. The rhodium(II)-acetate-catalyzed decomposition of 3-(4-acetoxyphenyl)-1-diazo-4-(pyrrol-1-yl)-2-butanone ( 5d ) gave 6-(4-acetoxyphenyl)-5,6-dihydro-7(8H)-indolizinone ( 6d ) in 82% yield via an intramolecular carbenoid reaction. The latter compound was converted in four steps in 13% overall yield to (±)-ipalbidine ( 1b ).     

Solid-state fermentation of agricultural wastes into food through pleurotus cultivation

The technical feasibility of using agricultural wastes (mango and date industry wastes) as a substrate for the cultivation ofPleurotus ostreatus NRRL-0366 is evaluated. When comparing the biological efficiency of mushroom production, the highest yield of fruiting bodies was obtained using a mixture of date waste and rice straw at a ratio (1:1) (11.96%), followed by a mixture 3:1 (11.16%). The lowest one was the mixture 2:1 (9.19%). FungusPleurotus ostreatus NRRL-0366 can also be cultivated on mango waste supplemented with rice straw at a different ratio. The best one was the 1:1 mixture (10.18%), whereas the lowest was a mixture 3:1 (6.4%). Comparing the results obtained favored the use of date waste as a substrate for growingPleurotus ostreatus NRRL-0366. Spawn was cultured on three different substrates as follows: Date waste alone (I); 1:1 (by wt) date waste and rice straw (II); 1:1:1 date waste, rice straw, and corncobs (III). Final dry weight and composition of the fruiting bodies are tabulated for the three sets of conditions. Date waste and rice straw mixture (II) is a good source of nonstarchy carbohydrate (67%) and protein (27.44%) containing amounts of essential amino acids, especially lysine and low RNA (3.81%). Elemental analysis were studied in the fruit bodies of the three media.     

Alkaloid extracts of Ficus species and palm oil-derived tocotrienols synergistically inhibit proliferation of human cancer cells

Tocotrienols have been reported to possess anticancer effects other than anti-inflammatory and antioxidant activities. This study explored the potential synergism of antiproliferative effects induced by individual alkaloid extracts of Ficus fistulosa, Ficus hispida and Ficus schwarzii combined with δ- and γ-tocotrienols against human brain glioblastoma (U87MG), lung adenocarcinoma (A549) and colorectal adenocarcinoma (HT-29) cells. Cell viability and morphological results demonstrated that extracts containing a mixture of alkaloids from the leaves and bark of F. schwarzii inhibited the proliferation of HT-29 cells, whereas the alkaloid extracts of F. fistulosa inhibited the proliferation of both U87MG and HT-29 cells and showed synergism in combined treatments with either δ- or γ-tocotrienol resulting in 2.2–34.7 fold of reduction in IC₅₀ values of tocotrienols. The observed apoptotic cell characteristics in conjunction with the synergistic antiproliferative effects of Ficus species-derived alkaloids and tocotrienols assuredly warrant future investigations towards the development of a value-added chemotherapeutic regimen against cancers.     

Über Alkaloide aus Laurelia novae-zelandiae A. CUNN. 5. Mitteilung über natürliche und synthetische Isochinolinderivate

From an extract of Laurelia novae-zelandiae A. CUNN . the aporphine alkaloids (?)-pukateine (I), (?)-pukateine methyl ether (II), (?)-roemerine (IV), (?)-mecambroline (V), (+)-boldine (VII), (+)-isoboldine (VIII), (+)-laurolitsine (IX), and the proaporphine alkaloid (+)-stepharine (X) were isolated. Compounds II and V were up to now not described as natural alkaloids. These and the alkaloids IV, VII, VIII, IX and X are new for L. novae-zelandiae.     

Lokalisierung der Ketogruppe in Inandenin-onen. 160. Mitteilung über Alkaloide

Localization of the keto group in Inandenin-ones . By Schmidt degradation of the spermidine alkaloids inandenine-12-on ( 1 ) and inandenine-13-on ( 2 ) from Oncinotis inandensis followed by hydrolysis, acetylation and esterification four different types of products were obtained: the dicarboxylic diesters 9 and 10 , the ω-amino-carboxylic esters 11 and 12 , the acetylated polyamines 14 and 15 , and the acetylated triaminecarboxylic esters 16 and 17 . By GLC. and mass spectral analysis of these degradation products, and by comparison with synthetic compounds it was possible to confirm the structures 1 and 2 . The same alkaloid mixture ( 1+2 ) was obtained from the leaves of Oncinotis nitida BENTH .     

Alkaloids ofHaplophyllum foliosum

The alkaloids skimmianine, dubinidine, foliosidine, graveoline, and compounds (I) and (II) have been isolated from the epigeal part of the plantHaplophyllum foliosum Vved. (family Rutaceae). On the basis of the spectral characteristics of (I) and its 0-isopropylidene derivative it has been established that the compound is the alkaloid edulinine. Substance (II) was identified as ferulic acid by direct comparison with an authentic sample. This is the first time that edulinine and ferulic acid have been detected in plants of the genusHaplophyllum.Institute of the Chemistry of Plant Substances of the Academy of Sciences of the Uzbek SSR, Tashkent. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 803–805, November–December, 1980.     

Structural and spectroscopic characterization of epiisopiloturine-metal complexes,and anthelmintic activity vs. S. mansoni

Epiisopiloturine (EPI), extracted from leaves of Pilocarpus microphyllus, a plant originally from the Amazon and Savanna regions in Brazil, was described as a potential drug against Schistosomiasis, a neglected severe disease. Herein, EPI was complexed with copper(II) or zinc(II) salts and the isolated species, [Cu(epi)₄](ClO₄)₂ (1) and [Zn(epi)₂Cl₂] (2), were structurally and spectroscopically characterized. By using X-ray diffraction, the crystal structures of both metal complexes were determined, indicating a square pyramidal geometry for copper for 1 and a tetrahedral environment around zinc for 2. EPR spectra of 1 show a typical tetragonal environment around the central metal ion with some tetrahedral distortion, both in the solid state and in frozen acetonitrile solution, in accordance with crystallographic data. For 2, NMR spectra have bands consistent with a tetrahedral species in solid state or in DMSO-d₆ solution. These spectroscopic characterization data were further supported by Density Functional Theory calculations, showing that these metal complexes are also stable in solution. Those metal complexes were tested against adult worms of Schistosoma mansoni, in comparison to the free alkaloid as anthelmintic agent. Coordination with copper(II) improved the alkaloid schistosomicidal properties, while binding to zinc(II) decreased its activity.     

Synthesis of certain tricyclic quinoline derivatives as potential antiamebal agents

Synthesis of the fused tricyclic systems, 1, 2, 3, 3a, 4, 5-hexahydropyrrolo[1, 2a]quinoline (I) and 2, 3, 4, 4a, 5, 6-hexahydro 1H-benzo[c]quinolizine (II), each bearing an ethoxyl substituent on the benzene ring, has been achieved. The compounds combine certain structural features of the alkaloid emetine and of 8-quinolinols.