Pyrrolidine Alkaloids Research Articles

The effects of comfrey derived pyrrolidine alkaloids on rat liver

Three groups of young adult rats were fed pyrrolizidine alkaloids derived from Russian comfrey to study the effects of the herb on the liver. Group I animals received a single dose of 200 mg/kg body wt, Group II 100 mg/kg three times a week for 3 weeks and Group III 50 mg/kg three times a week for 3 weeks. All rats showed light and electron-microscopic evidence of liver damage, the severity of which was dose dependent. There was swelling of hepatocytes and hemorrhagic necrosis of perivenular cells. There was a concomitant loss of sinusoidal lining cells with disruption of sinusoidal wall and the sinusoids were filled with cellular debris, hepatocyte organelles and red blood cells. Extravasation of red blood cells was evident. Terminal hepatic venules were narrowed by intimal proliferation, and in Group II and III, reiculin fibres radiated from these vessels. These appearances have been described in veno-occlusive disease due to pyrrolizidine alkaloids from other plant sources such as Senecio and Crotalaria. The safety of comfrey, a widely used herb, in relation to human consumption requires further investigation.

ChemInform Abstract: Synthesis of Two Pyrrolidine Alkaloids, Peripentadenine (Ia) and Dinorperipentadenine (Ib).

ChemInformVolume 21, Issue 16 Natural Products ChemInform Abstract: Synthesis of Two Pyrrolidine Alkaloids, Peripentadenine (Ia) and Dinorperipentadenine (Ib). J. P. MICHAEL, J. P. MICHAEL Dep. Chem., Univ. Witwatersrand, Wits 2050, South AfricaSearch for more papers by this authorA. S. PARSONS, A. S. PARSONS Dep. Chem., Univ. Witwatersrand, Wits 2050, South AfricaSearch for more papers by this authorR. HUNTER, R. HUNTER Dep. Chem., Univ. Witwatersrand, Wits 2050, South AfricaSearch for more papers by this author J. P. MICHAEL, J. P. MICHAEL Dep. Chem., Univ. Witwatersrand, Wits 2050, South AfricaSearch for more papers by this authorA. S. PARSONS, A. S. PARSONS Dep. Chem., Univ. Witwatersrand, Wits 2050, South AfricaSearch for more papers by this authorR. HUNTER, R. HUNTER Dep. Chem., Univ. Witwatersrand, Wits 2050, South AfricaSearch for more papers by this author First published: April 17, 1990 https://doi.org/10.1002/chin.199016302AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume21, Issue16April 17, 1990 RelatedInformation

Direct Substitution of 2-Benzenesulphonylpiperidines and -pyrrolidines by Carbon Nucleophiles: Synthesis of the Pyrrolidine Alkaloid Ruspolinone

Treatment of 2-benzenesulphonylpiperidines and -pyrrolidines with various carbon nucleophiles such as aryl, vinyl, and alkynyl organometallics (5 examples), or alternatively silyl enol ethers or allylsilanes in the presence of a Lewis acid (4 examples), afford the corresponding substitution products in good yield. The method has been used to prepare the pyrrolidine alkaloid natural product Ruspolinone (13).

Intramolecular alkylation of 3-hydroxypyrrole-2-carboxylates. Formation of [formula omitted], [formula omitted], and [formula omitted] ring systems related to pyrrolidine alkaloids

The intramolecular alkylation of 3-hydroxypyrrole-2-carboxylates 4, 8, and 12 leads to fused ring systems found in the pyrrolizidine, indolizidine, and related pyrrolidine alkaloids.

ChemInform Abstract: Alkynylation of Thiolactams. New Synthesis of α‐Substituted Pyrrolidine and Piperidine Alkaloids.

AbstractAlkynylation of S‐alkylthioamidium salts (III) of thiolactams (I) with lithium acetylides (IV) followed by LiAlH4 reduction yields α‐alkynylazacycloalkanes (V).

Alkynylation of thiolactams. New synthesis of α-substituted pyrrolidine and piperidine alkaloids

Alkynylation of S-alkylthioamidium salts of thiolactams with lithium acetylides followed by reduction with LiAIH4 provided α-alkynylazacycloalkanes, which on reduction, or hydroboration followed by oxidation, gave α-substituted pyrrolidine and piperidine alkaloids.

Synthesis of two pyrrolidine alkaloids, peripentadenine and dinorperipentadenine

Vinylogous amides 6 and 8 are key intermediates in syntheses of title alkaloids 1a and 1b .

Pyrrolidine, piperidine, and pyridine alkaloids.

The first page of this article is displayed as the abstract.

Identification by methane chemical ionization gas chromatography/mass spectrometry of the products obtained by steam distillation and aqueous acid extraction of commercial Piper methysticum.

Bornyl cinnamate has been identified as a constituent of kava resin and of the steam distillate of Piper methysticum. 5-Hydroxydihydrokawain was identified in commercial samples of P. methysticum originating from Vanuatu provided an initial aqueous extraction was employed. Commercial preparations, and fresh samples of the root of this plant from Fiji, lacked this compound. Two previously described N-cinnamoyl pyrrolidine alkaloids were also observed along with stigmasterol in kava resin from Fiji and Vanuatu. The products derived from aqueous 2 M hydrochloric acid extraction of P. methysticum were determined from methane chemical ionization gas chromatography/mass spectrometry analysis which identified a series of hydroxylated compounds (15a-d) derived from formal decarbonylation of the parent kava lactones. The products (13a-c) of dehydration of these compounds were also observed. The efficiency of kava resin extraction from plant material by water (the traditional method of preparation of the kava beverage) was typically 5-10% of that recovered by direct extraction with an organic solvent.

Further classification of skin alkaloids from neotropical poison frogs (Dendrobatidae), with a general survey of toxic/noxious substances in the amphibia

Abstract Cutaneous granular glands are a shared character of adult amphibians, including caecilians, and are thought to be the source of most biologically active compounds in amphibian skin. Data are available from one or more species in over 100 of nearly 400 genera comprising the three living orders of Amphibia. Many species contain unidentified substances judged to be noxious based on predator aversion or human taste. Additionally, there is a great diversity of known compounds, some highly toxic as well as noxious, which can be tabulated under four broad categories: biogenic amines, peptides, bufodienolides (bufogenins) and alkaloids . The last category includes alkaloids derived from biogenic amines, water-soluble alkaloids (tetrodotoxins) and lipophilic alkaloids. Most compounds are known only from skin of adult amphibians, but the toxic and noxious properties of eggs and larvae of certain salamanders and toads can be attributed to tetrodotoxins and bufodienolides, which occur also in adult tissues other than skin. Predator aversion and various antipredator behaviors and aposematic colorations clearly prove the defensive value of these diverse metabolites, whether or not they are elaborated primarily (e.g. alkaloids) nor secondarily (e.g. some peptides and biogenic amines) for this function. Lipophilic alkaloids include the samandarine alkaloids, known definitely only from an Old World genus of salamanders, and the more than 200 dendrobatid alkaloids. Nearly all the latter are unique to neotropical poison frogs of the genera Dendrobates and Phyllobates (Dendrobatidae), except for seemingly homoplastic occurrences of a few such alkaloids in small brightly colored anurans of several other families. Owing to recent discoveries and new structural information, the dendrobatid alkaloids are here partitioned among the following major and minor classes: batrachotoxins, histrionicotoxins, indolizidines, pumiliotoxin-A class and its allopumiliotoxin and homopumiliotoxin subclasses, decahydroquinolines, gephyrotoxins, 2,6-disubstituted piperidines, 2,5-disubstituted pyrrolidines, pyridyl-piperidines, indole alkaloids, azatricyclododecenes and amidine alkaloids . Except for the steroidal batrachotoxins, and the minor classes of pyrrolidine alkaloids, indole alkaloids and amidine alkaloids, all the above contain a piperidine ring. A large number of piperidine-based alkaloids occur mainly as trace compounds in Dendrobates and remain unclassified; the only water-soluble toxin so far discovered in a dendrobatid ( Colostethus ) is structurally unknown, but conceivably an alkaloid.

ChemInform Abstract: Electroorganic Chemistry. Part 96. Synthesis of Optically Active Piperidine and Pyrrolidine Alkaloids from L‐Lysine, L‐Ornithine, or L‐Proline Using Anodic Oxidation as Key Steps.

AbstractAnodic oxidation of the L‐lysine derivative (I) gives the piperidine (II) which is converted to (+)‐N‐methylconiine (V) via (III) and (IV).The pyrrolidine (VI) is produced from L‐proline or L‐ornithine and then transformed into the diastereomers (VII) in an analogues manner.

Further classification of skin alkaloids from neotropical poison frogs (dendrobatidae), with a general survey of toxic/noxious substances in the amphibia

Cutaneous granular glands are a shared character of adult amphibians, including caecilians, and are thought to be the source of most biologically active compounds in amphibian skin. Data are available from one or more species in over 100 of nearly 400 genera comprising the three living orders of Amphibia. Many species contain unidentified substances judged to be noxious based on predator aversion or human taste. Additionally, there is a great diversity of known compounds, some highly toxic as well as noxious, which can be tabulated under four broad categories: biogenic amines, peptides, bufodienolides (bufogenins) and alkaloids. The last category includes alkaloids derived from biogenic amines, water-soluble alkaloids (tetrodotoxins) and lipophilic alkaloids. Most compounds are known only from skin of adult amphibians, but the toxic and noxious properties of eggs and larvae of certain salamanders and toads can be attributed to tetrodotoxins and bufodienolides, which occur also in adult tissues other than skin. Predator aversion and various antipredator behaviors and aposematic colorations clearly prove the defensive value of these diverse metabolites, whether or not they are elaborated primarily (e.g. alkaloids) nor secondarily (e.g. some peptides and biogenic amines) for this function. Lipophilic alkaloids include the samandarine alkaloids, known definitely only from an Old World genus of salamanders, and the more than 200 dendrobatid alkaloids. Nearly all the latter are unique to neotropical poison frogs of the genera Dendrobates and Phyllobates (Dendrobatidae), except for seemingly homoplastic occurrences of a few such alkaloids in small brightly colored anurans of several other families. Owing to recent discoveries and new structural information, the dendrobatid alkaloids are here partitioned among the following major and minor classes: batrachotoxins, histrionicotoxins, indolizidines, pumiliotoxin-A class and its allopumiliotoxin and homopumiliotoxin subclasses, decahydroquinolines, gephyrotoxins, 2,6-disubstituted piperidines, 2,5-disubstituted pyrrolidines, pyridyl-piperidines, indole alkaloids, azatricyclododecenes and amidine alkaloids. Except for the steroidal batrachotoxins, and the minor classes of pyrrolidine alkaloids, indole alkaloids and amidine alkaloids, all the above contain a piperidine ring. A large number of piperidine-based alkaloids occur mainly as trace compounds in Dendrobates and remain unclassified; the only water-soluble toxin so far discovered in a dendrobatid ( Colostethus) is structurally unknown, but conceivably an alkaloid.

Structure of daechualkaloid-A, a new pyrrolidine alkaloid of novel skeleton from [formula omitted][formula omitted] var. [formula omitted

A new pyrrolidine alkaloid named daechualkaloid-A was isolated from the fruit of Zizyphus jujuba Miller var. inermis Rehder(Rhamnaceae), and its planer structure has been determined by spectroscopic methods.

Synthesis of optically active piperidine and pyrrolidine alkaloids from L-lysine, L-ornithine, or L-proline using anodic oxidation as key steps

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of optically active piperidine and pyrrolidine alkaloids from L-lysine, L-ornithine, or L-proline using anodic oxidation as key stepsTatsuya Shono, Yoshihiro Matsumura, Kenji Tsubata, and Kenshi UchidaCite this: J. Org. Chem. 1986, 51, 13, 2590–2592Publication Date (Print):June 1, 1986Publication History Published online1 May 2002Published inissue 1 June 1986https://doi.org/10.1021/jo00363a035RIGHTS & PERMISSIONSArticle Views809Altmetric-Citations97LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (415 KB) Get e-Alerts Get e-Alerts

Purification and properties of glucosidase I from mung bean seedlings

The microsomal enzyme fraction from mung bean seedlings was found to contain glucosidase activity capable of releasing [ 3H]glucose from the glucose-labeled Glc 3Man 9GlcNAc. The enzymatic activity could be released in a soluble form by treating the microsomal particles with 1.5% Triton X-100. When the solubilized enzyme fraction was chromatographed on DE-52, it was possible to resolve glucosidase I activity (measured by the release of [ 3H]glucose from Glc 3Man 9GlcNAc) from glucosidase II (measured by release of [ 3H]glucose from Glc 2Man 9GlcNAc). The glucosidase I was purified about 200-fold by chromatography on hydroxylapatite, Sephadex G-200, dextran-Sepharose, and concanavalin A-Sepharose. The purified enzyme was free of glucosidase II and arylglucosidase activities. Only a single glucose residue could be released from the Glc 3Man 9GlcNAc by this purified enzyme and the other product was the Glc 2Man 9GlcNAc. Furthermore, this enzyme was inhibited in a dose-dependent manner by kojibiose, an α-1,2-linked glucose disaccharide, but not by other α-linked glucose disaccharides. These data indicate that this glucosidase is a specific α-1,2-glucosidase. The pH optimum for the glucosidase I was about 6.3 to 6.5, and no requirements for divalent cations were observed. The enzyme was inhibited strongly by the glucosidase processing inhibitors, castanospermine and deoxynojirimycin, and less strongly by the plant pyrrolidine alkaloid, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine. However, the enzyme was not inhibited by the mannosidase processing inhibitors, swainsonine, deoxymannojirimycin or 1,4-dideoxy-1,4-imino- d-mannitol. The stability of the enzyme under various conditions and other properties of the enzyme were determined.

The synthesis from d-xylose of the potent and specific enantiomeric glucosidase inhibitors, 1,4-dideoxy-1,4-imino-d-arabinitol and 1,4-dideoxy-1,4-imin

Both enantiomers of 1,4-dideoxy-1,4-iminoarabinitol are specific inhibitors of glucosidases. The synthesis of 1,4-dideoxy-1,4-imino-D-arabinitol involves connecting C2 and C5 of xylose together with nitrogen, whereas the synthesis of 1,4-dideoxy-1.4-imino-L-arabinitol requires C1 and C4 of xylose to be joined together by nitrogen. 1,4-Dideoxy-1,4-imino-D-arabinitol is a naturally occurring pyrrolidine alkaloid found in Arachniodes standishii and Angylocalyx boutiqueanus .

Arginine decarboxylase as the source of putrescine for tobacco alkaloids

The putrescine which forms a part of nicotine and other pyrrolidine alkaloids is generally assumed to arise through the action of ornithine decarboxylase (ODC). However, we have previously noted that changes in the activity of arginine decarboxylase (ADC), an alternate source ofputrescine, parallel changes in tissue alkaloids, while changes in ODC activity do not. This led us to undertake experiments to permit discrimination between ADC and ODC as enzymatic sources of putrescine destined for alkaloids. Two kinds of evidence presented here support a major role for ADC in the generation ofputrescine going into alkaloids: (a) A specific ‘suicide inhibitor’ of ADC effectively inhibits the biosynthesis of nicotine and nornicotine in tobacco callus, while the analogous inhibitor of ODC is less effective, and (b) the flow of 14C from uniformly labelled arginine into nicotine is much more efficient than that from ornithine.

Correlation between polyamines and pyrrolidine alkaloids in developing tobacco callus.

Since the diamine putrescine can be metabolized into the pyrrolidine ring of tobacco alkaloids as well as into the higher polyamines, we have investigated the quantitative relationship between putrescine and these metabolites in tobacco callus cultured in vitro. We measured levels of free and conjugated putrescine and spermidine, and pyrrolidine alkaloids, as well as activities of the putrescine-biosynthetic enzymes arginine and ornithine decarboxylase. In callus grown on high (11.5 micromolar) alpha-naphthalene acetic acid, suboptimal for alkaloid biosynthesis, putrescine and spermidine conjugates were the main putrescine derivatives, while in callus grown on low (1.5 micromolar) alpha-naphthalene acetic acid, optimal for alkaloid formation, nornicotine and nicotine were the main putrescine derivatives. During callus development, a significant negative correlation was found between levels of perchloric acid-soluble putrescine conjugates and pyrrolidine alkaloids. The results suggest that bound putrescine can act as a pool for pyrrolidine alkaloid formation in systems where alkaloid biosynthesis is active. In addition, changes in arginine decarboxylase activity corresponding to increased alkaloid levels suggest a role for this enzyme in the overall biosynthesis of pyrrolidine alkaloids.

Stereoselective preparation of bicyclic lactams by copper- or ruthenium-catalysed cyclization of N-allyltrichloroacetamides: a novel entry to pyrrolidine alkaloid skeletons

Cyclization of certain N-allyltrichloroacetamides provides a stereoselective method for several bicyclic lactams.

The pyrrolidine alkaloid, 2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine, inhibits glycoprotein processing.

2,5-Dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP) is a pyrrolidine alkaloid that was isolated from the plant, Lonchocarpus sericeus. In the present study, DMDP was tested as an inhibitor of glycoprotein processing. MDCK cells were infected with influenza virus and the virus was raised in the presence of various amounts of DMDP. The glycoproteins were labeled by the addition of [2-3H]mannose or [1-3H]galactose to the medium. The virus was isolated by differential centrifugation and treated with Pronase to obtain glycopeptides. These glycopeptides were isolated by chromatography on Bio-Gel P-4, then digested with endoglucosaminidase H (Endo H) and rechromatographed on the Bio-Gel P-4 column. In the control virus, more than 70% of the glycopeptides were resistant to Endo H and were previously characterized as complex types of oligosaccharides. The remaining 20-25% are sensitive to Endo H and are of the high-mannose type. However, in the presence of DMDP (250 micrograms/ml), more than 80% of the glycopeptides are susceptible to digestion by Endo H. The oligosaccharide released by this treatment sized like a hexose11-12GlcNAc on a calibrated column of Bio-Gel P-4, and was only slightly susceptible to alpha-mannosidase treatment. This oligosaccharide was also labeled in the glucose moieties by growing the virus in [1-3H]galactose in the presence of DMDP. Following isolation, the oligosaccharide was subjected to complete methylation. Acid hydrolysis of the methylated oligosaccharide gave three methylated glucose derivatives, corresponding to 2,3,4,6-tetramethylglucose, 3,4,6-trimethylglucose, and 2,4,6-trimethylglucose in almost equal amounts. These data indicate that the oligosaccharide is a Glc3Man8-9-GlcNAc and that DMDP inhibits glucosidase I. Similar results were obtained with the cellular glycoproteins. DMDP did not inhibit the incorporation of [3H]leucine into protein in MDCK cells, nor did it inhibit virus production as measured by plaque counts or hemagglutination assays. DMDP did cause some inhibition of mannose incorporation into the lipid-linked monosaccharides, but incorporation into lipid-linked oligosaccharides was not greatly affected, and incorporation into protein was stimulated. These results suggest that the pyrrolidine alkaloids are a new class of processing inhibitors.