Rhoeadine

Identification and metabolite profiling of alkaloids in aerial parts of Papaver rhoeas by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.[Pubmed:29607619]

J Sep Sci. 2018 Jun;41(12):2517-2527.

Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like Rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty-five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and Rhoeadine-type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.

Variation of alkaloid contents and antimicrobial activities of Papaver rhoeas L. growing in Turkey and northern Cyprus.[Pubmed:28633584]

Pharm Biol. 2017 Dec;55(1):1894-1898.

CONTEXT: Papaver rhoeas L. (Papaveraceae) corn poppy, widely distributed in Turkey, is used to make a cough syrup for children, as a tea for disturbed sleep, for pain relief and as a sedative in folk medicine. OBJECTIVE: Samples of P. rhoeas collected from eight different locations in Turkey and three from northern Cyprus were investigated for their alkaloid content and screened for their antimicrobial activities. MATERIALS AND METHODS: From the aerial parts of P. rhoeas samples, alkaloids were isolated by column and preparative thin-layer chromatography. The alkaloids were identified by comparing their spectral data (UV, IR and (1)H-NMR) and TLC Rf values with those of authentic samples. The antimicrobial study was carried out by microbroth dilution technique against six strains of bacteria and three strains of fungi. RESULTS: Twelve different alkaloids belonging to proaporphine (mecambrine), aporphine (roemerine), promorphinan (salutaridine), protopine (coulteropine and protopine) and Rhoeadine (epiglaucamine, glaucamine, glaudine, isoRhoeadine, isorhoeagenine, Rhoeadine and rhoeagenine) groups were isolated. The most significant activity was observed with the alkaloid extract of P8 against Staphylococcus aureus with a MIC value of 1.22 mug/mL and against Candida albicans with a MIC value of 2.4 mug/mL. DISCUSSION: The results indicate that P. rhoeas samples (P8 and P9), which contain roemerine as their major alkaloid, were the most active extracts.

Characterization and origin of the 'B' and 'C' compounds in the acid/neutral forensic signatures of heroin - products from the acylation of porphyroxine and subsequent hydrolysis.[Pubmed:26593749]

Drug Test Anal. 2017 Mar;9(3):462-469.

Two significant compounds often found in the gas chromatographic analysis of the acid/neutral extracts from illicit heroin have remained uncharacterized for 30 years. The unknown compounds are referred to as the 'B' and 'C' compounds. It has been postulated that these compounds arise from acetylation of porphyroxine, a Rhoeadine alkaloid found at trace levels in the opium poppy, Papaver somniferum. Porphyroxine was isolated from opium and acetylated to produce N,O(8) -diacetylporphyroxine. Mild hydrolysis produced N,O(8) -diacetyl-O(14) -desmethyl-epi-porphyroxine (the C compound) and N-acetyl-O(14) -desmethyl-epi-porphyroxine (the B compound). Both N,O(8) -diacetyl-O(14) -desmethyl-epi-porphyroxine and N-acetyl-O(14) -desmethyl-epi-porphyroxine were determined to be C-14 epimers of porphyroxine and N,O(8) -diacetylporphyroxine. The non-epimerized isomers of the B and C compounds were also detected in illicit heroin, but at much lower levels. Chromatographic and spectroscopic data are presented for the aforementioned compounds. The presence/absence and relative concentrations of these compounds is presented for the four types of heroin (Southwest Asian, South American, Southeast Asian, and Mexican). The prevalence of detection for the B and C compounds are Southwest Asian = 92-93%, South American = 64-72%, Southeast Asian = 45-49%, and Mexican South American > Southeast Asian, each by an order of magnitude. These compounds were rarely detected in Mexican heroin. The presence/absence and relative concentrations of these compounds provide pertinent forensic signature characteristics that significantly enhance the final regional classifications. Copyright (c) 2015 John Wiley & Sons, Ltd.

Dioxygenases catalyze O-demethylation and O,O-demethylenation with widespread roles in benzylisoquinoline alkaloid metabolism in opium poppy.[Pubmed:23928311]

J Biol Chem. 2013 Oct 4;288(40):28997-9012.

In opium poppy, the antepenultimate and final steps in morphine biosynthesis are catalyzed by the 2-oxoglutarate/Fe(II)-dependent dioxygenases, thebaine 6-O-demethylase (T6ODM) and codeine O-demethylase (CODM). Further investigation into the biochemical functions of CODM and T6ODM revealed extensive and unexpected roles for such enzymes in the metabolism of protopine, benzo[c]phenanthridine, and Rhoeadine alkaloids. When assayed with a wide range of benzylisoquinoline alkaloids, CODM, T6ODM, and the functionally unassigned paralog DIOX2, renamed protopine O-dealkylase, showed novel and efficient dealkylation activities, including regio- and substrate-specific O-demethylation and O,O-demethylenation. Enzymes catalyzing O,O-demethylenation, which cleave a methylenedioxy bridge leaving two hydroxyl groups, have previously not been reported in plants. Similar cleavage of methylenedioxy bridges on substituted amphetamines is catalyzed by heme-dependent cytochromes P450 in mammals. Preferred substrates for O,O-demethylenation by CODM and protopine O-dealkylase were protopine alkaloids that serve as intermediates in the biosynthesis of benzo[c]phenanthridine and Rhoeadine derivatives. Virus-induced gene silencing used to suppress the abundance of CODM and/or T6ODM transcripts indicated a direct physiological role for these enzymes in the metabolism of protopine alkaloids, and they revealed their indirect involvement in the formation of the antimicrobial benzo[c]phenanthridine sanguinarine and certain Rhoeadine alkaloids in opium poppy.

Genetic and chemical components analysis of Papaver setigerum naturalized in Korea.[Pubmed:22921420]

Forensic Sci Int. 2012 Oct 10;222(1-3):387-93.

Of the 110 species of genus Papaver, only Papaver somniferum and P. setigerum are controlled poppies in Korea. All poppy samples share similar morphology therefore it is important to check if they contain controlled substances such as morphine and codeine for forensic purpose. Since the alkaloid content of Papaver plants varies according to their growing stage, chemical components analysis alone is not enough to identify exact species. In 2010, hundreds of poppy plants suspected to be P. somniferum were found in Jeju Island, South Korea. They had a slightly different but overall similar appearance to P. somniferum. Using GC-MS analysis, codeine, Rhoeadine, papaverine, protopine, noscapine, setigeridine and trace amounts of morphine were detected in these samples. Although their chemical components were different from what has been described in literatures for P. setigerum, they could be assumed to be P. setigerum based on their morphological features and GC-MS results. Also, chromosome numbers using their seeds showed 2n=44 and the numbers were in accordance with those of P. setigerum. Nucleotide substitution or insertion/deletion of ITS (internal transcribed spacer), 18S rRNA (ribosomal RNA), rbcL (large subunit of ribulose 1,5-bisphosphate carboxylase), trnL-trnF IGS (intergenic spacer), trnL intron and psbA-trnH were assessed as universal genetic markers for P. setigerum. Also, genetic analysis using six target genes involved in the biosynthesis of benzylisoquinoline alkaloids, including TYDC (tyrosine/dopa decarboxylase), SAT (salutaridinol-7-O-acetyltransferase), BBE (berberine bridge enzyme), COR (codeinone reductase), CYP80B1 ((S)-N-methylcoclaurine 3'-hydroxylase) and NCS (norcoclaurine synthase) were tested as Papaver-specific genetic markers by the existence of their PCR products. From the results, the sequences of the 6 universal genetic markers and 6 Papaver-specific genetic markers for P. setigerum were identified and then Genbank accession numbers of them were registered in NCBI. Also, the trnL intron and psbA-trnH nucleic acid sequences of the 7 Papaver species were identified and registered.

Isolation of triniifoline, miltanthaline and some medicinally important alkaloids from Papaver triniifolium.[Pubmed:9434617]

Planta Med. 1997 Dec;63(6):575-6.

New alkaloids, (+)-triniifoline, (+)-O-ethyltriniifoline (Rhoeadine type), and (+)-miltanthaline (benzylisoquinoline type) have been isolated from aerial parts of Papaver triniifolium Boiss, (Papaveraceae). The major alkaloids were medicinally important (-)-alpha-narcotine and papaverine together with (-)-mecambrine in the species whereas narceine and (-)-N-methylcrotonosine were minor alkaloids. The known (-)-alpha-narcotine, narceine and (-)-N-methylcrotonosine have been isolated for the first time from P. triniifolium.

Comparison of chemical and botanical studies of Turkish papaver belonging to the section pilosa.[Pubmed:17342603]

Planta Med. 1985 Oct;51(5):431-4.

The alkaloidal contents of the Turkish PAPAVER belonging to the section PILOSA have been studied by high performance liquid chromatography. According to the results obtained, the section PILOSA should be divided into two subsections; the first being characterised by the presence of the alkaloids amurine, glaucine and roemerine and the second by protopine and Rhoeadine. These conclusions were confirmed by the botanical studies.

Alkaloids from Papaver triniifolium of Turkish Origin1.[Pubmed:17405010]

Planta Med. 1983 Sep;49(9):43-5.

The major alkaloids of PAPAVER TRINIIFOLIUM collected in two different parts of Anatolia have proved to be of the aporphine, morphinane and Rhoeadine types. The two collections possessed different major alkaloids and the existence of chemical strains is indicated. In addition to the aporphine-(floripavidine), the morphinandienone-(amurine and salutaridine), benzylisoquinoline-(papaverine), proaporphine-(mecambrine) and tetrahydroprotoberberine-(sinactine, scoulerine and cheilanthifoline) type alkaloids have been isolated as minor alkaloids.

Alkaloids from Papaver cylindricum.[Pubmed:17396967]

Planta Med. 1982 Nov;46(3):175-8.

The major alkaloids obtained from Papaver cylindricum Cullen were oripavine, narcotine, thebaine and Rhoeadine. Floripavidine, papaverine, salutaridine, armepavine, N-methylasimilobine, scoulerine and cheilanthifoline were obtained as minor alkaloids. There have been no previous reports of alkaloids from P. cylindricum.

[Isolation and chemistry of the alkaloids from plants of the Papaveraceae, LXXXI Glauca - a new section of the genus Papaver].[Pubmed:17401829]

Planta Med. 1981 Feb;41(2):119-23.

On the basis of alkaloidal, morphological and chromosomal studies, the section Mecones Bernh. (Syn.: Papaver L., sect. Papaver) has been subdivided into two sections. Thus the new section Glauca J. Novak includes the species Papaver glaucum Boiss. et Hausskn., P. gracile Auch. and P. decaisnei Hochst. et Steud., whereas the section mecones Bernh. only the species P. somniferum L. and P. setigerum Dc. The major alkaloids of the species of the section mecones are the morphinane alkaloids morphine and codeine, whereas those of the section Glauca the Rhoeadine and the papaverrubines. The section mecones has the basic chromosome number x = 11, and the section Glauca x = 7. The basic chromosome numbers have been correlated with the morphological features.

Alkaloids from Papaver armeniacum, P. fugax and P. tauricola.[Pubmed:17401828]

Planta Med. 1981 Feb;41(2):105-18.

Species from the section Miltantha are reviewed in the context of their contained alkaloids. Thebaine was isolated as the major alkaloid from a sample of P. fugax together with narcotine, pronuciferine, alpinigenine, O-ethylalpinigenine, amurensinine, N-methyl-crotonosine, armepavine, isocorydine and salutaridine as minor alkaloids. A second sample of P. fugax contained glaucamine and glaudine as major alkaloids with Rhoeadine, oreogenine, oreodine and O-ethyl-glaucamine as minor alkaloids. Pronuciferine and armepavine were isolated as the major alkaloids from a sample of P. tauricola with narcotine, roemerine, nuciferine, nantenine and protopine as minor alkaloids. Another sample of P. tauricola yielded pronuciferine and mecambrine as major alkaloids with armepavine, lirinidine, thebaine and cryptopine as minor alkaloids. A sample of P. armeniacum contained Rhoeadine and rhoeagenine as major alkaloids with lirinidine, cryptopine, glaudine and O-ethylrhoeagenine as minor alkaloids. Some 25 alkaloids representing 9 different alkaloidal-types were obtained from extracts of the three Miltantha species. The results show that at least three different chemical races of P. fugax and P. armeniacum exist in which either 1-benzyltetrahydroisoquinoline-, proaporphine-, aporphine- or morphinane- or Rhoeadine- types are the major alkaloids. There are at least two different chemical strains of P. tauricola which contain either 1-beuzyltetrahydroisoquinoline-, proaporphine-, aporphine- or Rhoeadine- types as the major alkaloids.

Alkaloids from Egyptian Papaver rhoeas.[Pubmed:17401817]

Planta Med. 1981 Jan;41(1):61-4.

N-methylasimilobine was isolated as the major alkaloid from an Egyptian sample of P. RHOEAS L. Other alkaloids isolated from the same plant material were stylopine, coptisine, isocorydine and Rhoeadine. Chromatography indicated the presence of at least nine other minor alkaloids.

Isolation and chemistry of alkaloids from plants of the family Papaveraceae LXVII: Corydalis cava (L.) Sch. et K. (C. tuberosa DC).[Pubmed:1255467]

J Pharm Sci. 1976 Feb;65(2):294-6.

From Corydalis cava (L.) Sch. et K. (C. tuberosa DC) (Papaveraceae: genus Corydalis Med.), a mixture of alkaloids (0.53%) was isolated. The main alkaloid was (+)-bulbocapnine, and the minor alkaloids were coptisine, (+)-domestine, adlumidiceine, (+)-predicentrine, protopine, (-)-capnoidine, (+)-stylopine, (+)-isoboldine, 8-oxocoptisine, 1,2-methylenedioxy-6a,7-dehydroaporphine-10,11-quinone, and corysamine. In addition, fumaric acid was obtained. Coptisine, adlumidiceine, predicentrine, 8-oxocoptisine, corysamine, 1,2-methylenedioxy-6a, 7-dehydroaporphine-10,11-quinone, and isoboldine were found in C. cava for the first time, but Rhoeadine and papaverrubine alkaloids were not detected. Predicentrine and isoboldine were identified on the basis of the UV, IR, mass, and PMR spectra.