Tetrahydroprotoberberine Alkaloids Research Articles

Partial purification and properties of S-adenosyl-l-methionine: (S)-tetrahydroprotoberberinecis-N-methyltransferase from suspension-cultured cells of Eschscholtzia and Corydalis

An enzyme has been found in different species of isoquinoline alkaloid-producing plant cell cultures which specifically N-methylates certain (S)-tetrahydroprotoberberine alkaloids such as (S)-canadine and (S)-stylopine at the expense of S-adenosyl-l-methionine (SAM). It was partially purified (90-fold from Eschscholtzia californica cell suspension cultures and characterized. The enzyme has a pH optimum of 8.9, a temperature optimum at 40° and a Mr of about 78 000 ± 10%. The Km for (S)-canadine was determined to be 6.4,μM, for (S)-stylopine 3.1 μM and for SAM 12,μM. The enzyme is inhibited by S-adenosyl-l-homocysteine (SAH with a Ki of 24 μM.

Synthesis of Some Thieno Analogs of the Protoberberine and Protopine Skeletons. X-Ray Crystal Structure of 9,10-Dimethoxy-5-methyl-4,5,6,7,12,13-hexahydrothieno[3,2-e][3]benzazeci n-12-one

The preparation of the tetracyclic derivatives, (5) and (11), thienanalogues of the tetrahydroprotoberberine alkaloids, is described. Cyanogen bromide-induced water solvolysis of these isomeric compounds proceeded by different routes. 9,10-Dimethoxy-4,7,12,12a- tetrahydro-5H-benzo[g] thieno [3,2-a] quinolizine (11) under these conditions gave as the major product 4-(2-hydroxymethyl-4,5- dimethoxybenzyl )-4,5,6,7-tetrahydrothieno[3,2-c]pyridine-5- carbonitrile (12); no azecino derivatives were detected. By contrast such cleavage of 2,3-dimethoxy-5,8,12,12a-tetrahydro-6H- benzo [a] thieno [3,2-g] quinolizine (5) gave a major solvolytic ring- expanded product, 12-hydroxy-9,10-dimethoxy-4,5,6,7,12,13- hexahydrothieno [3,2-e][3]benzazecine-5-carbonitrile (15), and a minor elimination product, (E)-9,10-dimethoxy-4,5,6,7-tetrahydrothieno[3,2- e][3]benzazecine-5-carbonitrile (16). These last two compounds are examples of a new tricyclic ring system. From functional group interconversions of (15) was derived the N- methyl ketone (18), the first thieno analogue of the protopine alkaloid system. The crystal and molecular structure of this compound, 9,10-dimethoxy-5-methyl-4,5,6,7,12,13-hexahydrothieno[3,2-e][3] benzazecin - 12-one (18), has been determined by single-crystal X-ray methods.

The isolation and characterization of a new tetrahydroprotoberberine alkaloid from Corydalis clarkei.

The MeOH extract of Corydalis clarkei Prain yielded two tetrahydroprotoberberine alkaloids that bear the unusual 1,2- and 9, 10-tetraoxygenated substitution pattern observed previously only in caseanidine . The alkaloids have been identified as caseanidine (1) and the new alkaloid, clarkeanidine (2). The 1H- and 13C-nmr shifts of both alkaloids have been assigned unambiguously using 2-D nmr. The elucidation of the structure of 2 was achieved by comparison of the 1H- and 13C-nmr spectra of 2 with those of caseanidine coupled with additional spectroscopic evidence.

Syntheses of (±)-tetrahydropalmatine and spirobenzylisoquinolines by thermolysis of benzocyclobutene derivatives

The tetrahydroprotoberberine alkaloid, (±)-tetrahydropalmatine (1) was synthesized by heating the 1-benzocyclobutenyl-3,4-dihydroisoquinoline (16), followed by reduction of the dehydro compound (20) with sodium borohydride. Ochotensine type spirobenzylisoquinolines (18) and (19) were prepared by the electrocyclic reaction of the corresponding benzocyclobutene derivatives (14) and (15).

Intermolecular O‐methylation during EIMS of quaternary methoiodides of isoquinoline alkaloids

AbstractQuaternary methoiodides of tetrahydroprotoberberine (THB) alkaloids (1‐8) tend to undergo preionization degradation in the mass spectrometer at elevated temperatures. Different reaction pathways have been found in relation to the structure of the substance studied. Permethylated alkaloids, e.g. tetrahydropalmatine‐CH3I (8), give predominantly the Hofmann degradation intermediates and the fragment ions derived therein, while the alkaloids with free phenolic group(groups), as exemplified by scoulerine‐CH3I (1), show a greater tendency to be methylated by an intermolecular CH3 transfer mechanism: magnified image The latter process has been systematically studied and the mechanism substantiated through comparison of the spectra of analogous series, B/E linked scan and CD3 labelling. Similar behaviour has been observed in bisbenzyltetrahydroisoquinoline alkaloids.

Kinetics and product distribution in Pictet-Spengler cyclization of tetrahydropapaveroline to tetrahydroprotoberberine alkaloids

Kinetics and product distribution in Pictet-Spengler cyclization of tetrahydropapaveroline to tetrahydroprotoberberine alkaloids

1HNMR Chemical Shift Values for Aromatic Protons in 2,3,9,10- and 2,3,10,11-tetrasubstituted Tetrahydroprotoberberine Alkaloids

The (1)HNMR (CDCl (3)) data on 28 tetrahydroprotoberberine alkaloids have shown that it is possible, from the chemical shift values observed for the aromatic protons, not only to determine the substitution pattern but also the type of substituents carried on the two sites in rings A and D within this class of alkaloids.

Absolute configuration and biosynthesis of (+)-sinactine

The incorporation of norreticuline, reticuline and nororientaline into sinactine in Cocculus laurifolius DC has been studied and specific utilization of reticuline demonstrated. Feeding with N-[ 14CH 3]reticuline showed that the C atom 8 in sinactine is derived from N-Me group of reticuline. Feeding of (±)-[1- 3H, 3- 14C]norreticuline and degradation of biosynthetic sinactine established that the regiospecificity is maintained in the bioconversion of 1-benzyltetrahydroisoquinoline precursor into the tetrahydroprotoberberine alkaloid. Further feeding of doubly labelled precursor demonstrated that the H atom at the asymmetric centre in reticuline is retained in the bioconversion into sinactine. Feedings of labelled scoulerine and tetrahydropalmatrubine established the intermediacy of scoulerine in the biosynthesis and suggested that the methylenedioxy group formation probably precedes O-methylation in the bioconversion of scoulerine into sinactine. Parallel feedings of (R)-, and (S)-reticulines and chemical conversion of (+)-sinactine into (+)-(R)-tetrahydropalmatine established that (+)-sinactine has R-configuration at the asymmetric centre C-13a.

Analysis of Dopamine-Derived Tetrahydroisoquinoline and Tetrahydro-Protoberberine Alkaloids by Cation-Exchange Liquid Chromatography

Abstract Liquid chromatogrophic characteristics of twelve selected dopamine-derived tetrahydroisoquinoline and tetrahydroprotoberberine alkaloids on commercially available 10 μ cation-exchange columns (Partisil 10 SCX, Vydac TP 401 SCX and Nucleosil SA) were examined. Effects of mobile phase ionic strength, pH, addition of organic modifiers, and column temperature on retention and efficiency were determined. Capacity factors (k') were linear with respect to 1/ionic strength for Nucleosil and Vydac, but not for Partisil columns. Retention of compounds varied as follows: Nucleosil > Vydac > Partisil. Mobile phase pH had little effect on retention or selectivity. However, chromatographic efficiency was adversely affected by mobile phase pH greater than 5.5. Organic modifiers decreased elution time in the following order: 1-butanol > dioxane > 2-propanol ≃ acetonitrile > ethanol. Elevated column temperature decreased capacity factors and increased efficiency. Conditions for the separation and detection of low...

ChemInform Abstract: CONFORMATIONS, DNA BINDING PARAMETERS, AND ANTILEUKEMIC ACTIVITY OF CERTAIN CYTOTOXIC PROTOBERBERINE ALKALOIDS

AbstractUntersucht werden die Alkaloide (I)‐(VII) auf KB‐Cytotoxizität (in vitro) und auf Wirkung gegen P388‐Leukämie (in vivo).

Conformations, DNA binding parameters, and antileukemic activity of certain cytotoxic protoberberine alkaloids

The tetrahydroprotoberberine alkaloids 5 and 7 possessing a trans-quinolizidine conformation display in vitro KB cytotoxicities in contrast to their corresponding diastereomers 4 and 6 which exist in the cis-quinolizidine conformation and are much less toxic. The DNA-binding parameters of these compounds as well as the protoberberine salts 1, 8, and 9 have been examined by equilibrium dialysis. Only the quaternary salts bind to DNA. The alcohol 5 showed low in vivo activity against leukemia P388 systems, while the quaternary salts 8 and 9 proved to be toxic to the host.

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.

Neuroamine-derived alkaloids: Substrate-preferred inhibitors of rat brain monoamine oxidase in vitro

The effects of tetrahydropapaveroline (THP), salsolinol (SAL) and various hydroxylated and methoxylated tetrahydroprotoberberine (THPB) alkaloids on monoamine oxidase (MAO) forms A and B in rat brain homogenates were investigated. The substrates utilized were serotonin, a specific substrate for type A MAO; tyramine, a substrate for both type A and B MAO; and benzylamine, a preferred substrate for type B MAO. The concentrations of THP, SAL, 2,3,9,10-tetrahydroxyberbine and 2,3,10,11-tetrahydroxyberbine producing 50 per cent inhibition (I 50) of the oxidation of serotonin were 1.0 mM, 0.25 mM, 0.24 mM and 0.04 mM, respectively. In marked contrast, the I 50 concentrations of these alkaloids with benzylamine as substrate were 4.4 mM, 50 mM, 5.6 mM and 13 mM, respectively. These findings indicated that SAL and the tetrahydroxyberbines were substrate-preferred inhibitors of type A MAO whereas THP was a relatively nonspecific inhibitor of rat brain MAO. Kinetic data revealed that THP, SAL and 2,3,10,11-tetrahydroxyberbine inhibited the oxidation of serotonin in a typical competitive manner with apparent K i values of 0.82 mM, 0.11 mM and 0.05 mM, respectively. THP and SAL noncompetitively inhibited benzylamine oxidation with apparent K i values of 5.0 mM and 52 mM, respectively, while 2,3,10,11-tetrahydroxyberbine competitively inhibited the oxidation of benzylamine with an apparent K i of 3.8 mM. Sequential replacement of the hydroxyl groups at the 2,3,9,10 and 11 positions of the berbine ring system by methoxyl groups substantially decreased the potency and selectivity of MAO inhibition. The interaction of these alkaloids with the metabolic pathways of neurotransmitters suggests that these compounds may be of relevance in the modification of central synaptic function.

The fluorescence properties of protoberberine and tetrahydroprotoberberine alkaloids

The fluorescence properties of protoberberine and tetrahydroprotoberberine alkaloids

ChemInform Abstract: STRUCTURE ELUCIDATION OF TWO NEW TETRAHYDROPROTOBERBERINE ALKALOIDS, CORYTENCHINE (I) AND CORYTENCHIRINE (II)

Chemischer InformationsdienstVolume 6, Issue 44 Natural Products ChemInform Abstract: STRUCTURE ELUCIDATION OF TWO NEW TETRAHYDROPROTOBERBERINE ALKALOIDS, CORYTENCHINE (I) AND CORYTENCHIRINE (II) S. T. LU, S. T. LUSearch for more papers by this authorT. L. SU, T. L. SUSearch for more papers by this authorT. KAMETANI, T. KAMETANISearch for more papers by this authorA. UJIIE, A. UJIIESearch for more papers by this authorM. IHARA, M. IHARASearch for more papers by this authorK. FUKUMOTO, K. FUKUMOTOSearch for more papers by this author S. T. LU, S. T. LUSearch for more papers by this authorT. L. SU, T. L. SUSearch for more papers by this authorT. KAMETANI, T. KAMETANISearch for more papers by this authorA. UJIIE, A. UJIIESearch for more papers by this authorM. IHARA, M. IHARASearch for more papers by this authorK. FUKUMOTO, K. FUKUMOTOSearch for more papers by this author First published: November 4, 1975 https://doi.org/10.1002/chin.197544391Read the full textAboutPDF 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 onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume6, Issue44November 4, 1975 RelatedInformation

Inhibition of catecholamine uptake and retention in synaptosomal preparations by tetrahydroisoquinoline and tetrahydroprotoberberine alkaloids

The effects of racemic mixtures of representative tetrahydroisoquinoline and tetrahydroprotoberberine alkaloids on the mechanisms of catecholamine uptake and retention were studied in synaptosomal preparations from whole rat brain. The synaptosomes were incubated with ( 14 C)-d,l- norepinephrine or ( 14C)-dopamine in the presence of various concentrations of salsolinol (SAL), tetrahydropapaveroline (THP), 2,3,10,11-tetrahydroxyberbine (THB), or 2,3,10,11-tetramethoxyberbine (TMB). Levels of radioactivity in synaptosomes preloaded with labeled norepinephrine were significantly diminished by the addition of 10 −4 M THP, THB or SAL to approximately 42.7 per cent (P < 0·001), 85.8 per cent (P < 0·02) and 85.9 per cent (P < 0·01), respectively, of control preparations. THP, 10 −5 M, also significantly decreased synaptosomal retention of the labeled neuroamine. ( 14C)-dopamine was used in an analysis of alkaloid effects on catecholamine uptake kinetics. K i values obtained were: 0·7 × 10 −5 M (THP); 3·5 × 10 −5 M (THB); 1·25 × 10 −4 M (SAL); and 2·2 × 10 −4 M (TMB). These results have been interpreted to suggest that the affinity of these amine-derived alkaloids for the catecholaminergic uptake mechanisms, although not marked when compared to that of dopamine or norepinephrine, may be sufficient under conditions of highly localized formation and accumulation to have important physiological sequelae.

Structure Elucidation of Two New Tetrahydroprotoberberine Alkaloids, Corytenchine and Corytenchirine

Structure Elucidation of Two New Tetrahydroprotoberberine Alkaloids, Corytenchine and Corytenchirine

Detection of 9-methoxy substitution in tetrahydroprotoberberine alkaloids by mass spectrometry.

Abstract9‐Methoxytetrahydroprotoberberines are found to exhibit pronounced (MOCH3)+ ions in their mass spectra as opposed to isomers or homologs lacking such substitution, yet carrying methoxyl substituents at other sites. Locating such substituents originally present, or produced from 9‐hydroxy groups by treatment with diazomethane, allows to differentiate 9, 10‐ from 10, 11‐oxygenation patterns in ring D, and thus to secure an important step in the structure elucidation of unknown alkaloids of this class.

The structure of discretamine, a tetrahydroprotoberberine alkaloid.

AbstractOn the basis of mass spectrometric analysis, including comparison with closely related isomers, discretamine is proposed to have the structure of a 3,10‐dihydroxy‐2,9‐dimethoxytetrahydroprotoberberine.

Zur Rolle eines Reticulin-umwandelnden Enzyms (Berberin-Brücken-Enzym) im pflanzlichen Benzylisochinolin-Stoffwechsel

Investigations on the role of the reticuline converting enzyme for the biosynthesis of tetrahydro-protoberberine (THPB) alkaloids gave the following results: 1. The enzyme activity in cell suspension cultures of Macleaya microcarpa increases before onset of the biosynthesis of THPB alkaloids. 2. The reticuline converting enzyme and THPB metabolism show a concomitant presence in different plant species. 3. The enzyme converts not only (±)-reticuline but also (±)-laudanidine into THPB alkaloids. Obviously, it is specialized in the conversion of certain benzyltetrahydroisoquinoline alkaloids. An essential prerequisite for the enzymatic reaction seems to be the hydroxyl group at the C-atom 3′ of the given skeleton. — According to these findings we propose to replace the name “reticuline converting enzyme” by “berberine bridge enzyme”.