Alkaloids quaternary protoberberine

Several investigators analyzed quaternary protoberberine alkaloids by means of reversed-28 30 39 30... 

The structure of tetrahydrothalifendine(l94 RX + R2 = CH2,R3 = R5 = H, R4 — Me), from Thalictrum fendleri, was elucidated by spectral interpretation and chemical correlation with thalifendine (193 R1 + R2 = CH2, R3 = Me, R4 = H) which had been isolated from the same plant species.30 It appears that the isolation of a quaternary protoberberine alkaloid from a particular plant forecasts the discovery of the corresponding tetrahydro-alkaloid therein. 

A one-step synthesis of the protoberberine alkaloid karachine (18), employing a presumed Mannich reaction of 4-methyl-2-trimethylsilyloxy-2,4-pentadiene with berberine, has been detailed by Stevens and Pruitt.154 It is plausible that the initial step of the one-flask reaction sequence leading to karachine is, in fact, a [4+ + 2] cycloaddition of the quaternary aromatic salt, berberine chloride, with the terminal electron-rich olefin of the silyloxydiene [Eq. (70)]. 

Alkaloids which inhibit acetylcholine esterase, monoamine oxidase and catechol-O-methyltransferase are tabulated in Table 11. Potent ACE blocker are indole alkaloids of the physostigmine type (e.g., eseramine, geneserine, physovenine, eserine), protoberberine alkaloids (e.g., berberine, columbamine, coptisine, jatrorrhizine, palmatine), steroidal alkaloids (leptine I, solanine, solamargine, and tomatidine), galanthamine and others. A plausible structure-function relationship is not apparent, except that all these alkaloids have a quaternary N under physiological conditions, and that an oxygen can be traced 2 to 4 carbons adjacent to the N, similar to the situation in acetylcholine. 

These vesicles could be detected in Berberis as well as in Coptis (ref. 27) and seem to be the general principle for the biosynthesis and the transport of protoberberines. Once reticuline has entered this vesicle its fate to be metabolized to protoberberine alkaloids is determined. Since the quaternary end products are not able to pass membranes these vesicles also seem to be the transport vehicles to the final storage compartment, the vacuole. Electron microscopic pictures show that they seem to fuse with the vacuole and release their contents into it (ref. 29) which strongly supports this assumption. 

All of these enz)mes are associated with specific vesicles, most likely derived from smooth endoplasmic reticulum. Because of the charge of the quaternary protoberberine alkaloids, the alkaloids do not leave the vesicles, but ultimately end up in the vacuole when the vesicle membrane fuses with the tonoplast (Hartmann, 1991). 

Most protoberberine alkaloids occur in nature as tetrahydroprotober-berines or as quaternary protoberberinium salts. However, in the last few years a number of quaternary iV-methyltetrahydroprotoberberine salts as well as 7V-oxides have been reported. In addition to the usual substitution pattern, the C-8 position may bear a methyl group as in the naturally occurring protoberberine alkaloid ( —)-corytenchirine. Two recently reported retroprotoberberines are TV-methyl- and iV,(9-dimethylmecambridine the chemistry, synthesis, pharmacology, and biogenesis of the protoberberine alkaloids have been reviewed. 

Quaternary protoberberine chlorides, including berberine, palmatine, jatrorrhizine, coptisine, and dehydrocorydaline, cause marked contraction of uterine muscle, but only weak spasmolytic activity on isolated mouse intestine. Protoberberine alkaloid bearing plants which exhibit abortifacient and uterine stimulant properties have been reviewed by Farnsworth and co-workers." ... 

Liu et al. developed NACE methods for analysis of quaternary protoberberine alkaloids in Chinese herbal medicines by using LIE detection. It was found that the native fluorescence signal of the analytes decreased in mixtures of ACN methanol compared to that observed in pure solvents thus, it was suggested that the optimization of solvent system composition for sensitive LIE detection has to be carried out by considering this effect [68, 69]. 

Plants that contain protoberberine alkaloids are reported to be used as analgesics, antiseptics, sedatives, and stomatics in Chinese folk medicine. In Indian and Islamic folk medicine, such plants are used for bleeding disorders and eye diseases, and as antiseptics, sedatives, stomatics, and uterine muscle depressants. Both quaternary alkaloids and their tetrahydro derivatives possess many substantiated biological and therapeutic effects, e.g., pahnatine, jatrorrhizine, and tetrahydropahnatine have been reported to show in vitro antimalarial activity. In China, tetrahydropalmatine is used as an analgesic, and has been reported to exhibit bradycardial, hypotensive, and sedative activities 4). 

The general name protoberberine alkaloid is given to quaternary alkaloids possessing the same skeleton as berberine. The positions of the oxygen functions... 

Grycova et al. [79] reviewed the Uterature of quaternary protoberberine alkaloids in early 2007. Although HMBC data were discussed in... 

Covalent Bonding of Azoles to Quaternary Protoberberine Alkaloids... 

L. Grycova, J. Dostal, R. Marek, Quaternary protoberberine alkaloids. Phytochemistry 68 (2007) 150—175. 

L. Grycova, D. Hulova, L. Maier, S. Standara, M. Necas, F. Lemiere, R. Kares, J. Dostal, R. Marek, Covalent bonding of azoles to quaternary protoberberine alkaloids, Magn. Reson. Chem. 46 (2008) 1127-1134. 

The first part of this dissertation documents the isolation and identification of seven quaternary alkaloids from extracts of the roots of Thalictrum cultratum Wall., including six protoberberines (berberine, columbamine, jatrorrhizine, palmatine, (+)-thalidastine, and thalifendine) and one aporphine (magnoflorine). This research resulted in one publication [20]. 

Fluorescence data for the interaction with acetylcholinesterase (EC 3.1.1.7, ACHE) from the electric eel Electrophorus electricus with some quaternary protoberberine and benzophenanthridine alkaloids was obtained. Berberine and other related compounds were bound to the gamma y-anionic site of ACHE via a comparison with known inhibitors of acetylcholinesterase, including tetramethylammonium and tacrine. Furthermore, during the interaction, two molecules of the ligand were bound to one molecule of the enzyme [226]. 

Some protoberberine and structurally related alkaloids were tested for inhibitory activity on porcine pancreatic elastase (PPE) and human sputum elastase (HSE). Berberine chloride significantly inhibited the elastolytic activity of both enzymes, but tetrahydroberberine had no effect. It appears that the quaternary nitrogen atom of these alkaloids plays an important role in the inhibition of elastolytic activity. The amidolytic activity of the elastases was not affected by any of the test alkaloids [240]. 

Although the quaternary structure is assigned to the alkaloids of protoberberine type, it is of interest to note that during isolation they are frequently extracted into chloroform from either the basic or the acidic media. This phenomenon has been explained (97, 438) by the formation of a labile complex XI between the alkaloid and chloroform. 

In comparison with the other species belonging to the tribe Chelidonieae, Hylomecon vernalis Maxim., indigenous to the Far East, contains only small quantities of alkaloids (140), In the roots, 65% are quaternary benzophe-nanthridines the aerial part contains protoberberines, protopines, and benzophe-nanthridines (Tables XLII and XLIII). 

The Papaveraceae and Fumariaceae DC. are closely related families. Their relationship as well as their independence are well demonstrated by the external stmcture of the flowers, the various anatomical characteristics of their different organs, and alkaloid content. As in the Papaveraceae, the protoberberines, ben-zophenanthridines, and protopines are chemotaxonomically significant for the Fumariaceae. Characteristic for the Fumariaceae is the presence of spirobenzylis-oquinolines, indenobenzazepines, secophthalideisoquinolines, phthalideiso-quinolines, and cularines. The Fumariaceae also contain quaternary highly polar alkaloids, insoluble in nonpolar solvents (16). 

Bourdat-Deschamps, M. Herrenknecht, C. Akendengue, B. Laurens, A. Hocquemiller, R. Separation of protoberberine quaternary alkaloids from a cmde extract of Enantia chlorantha by centrifugal partition chromatography. J. Chromatogr. A, 2004,1041 (1-2), 143-152. 

The most widely spread alkaloids of the families Papaveraceae and Fumariaceae are protopine (3), magnoflorine (4), quaternary protoberberines (5) and quaternary... 

The above-ground parts of C. olivascens Bameby et Krukoff have yielded the bis-benzyltetrahydroisoquinolines (—)-2-norlimacine (20a), a new base (—)-caryolivine (20c), and l,2-dehydro-2-norlimacusine (21a) as the principal components of the alkaloid mixture (412). On the other hand, the fruits have furnished eight non-quaternary bases, including (H-)-coclaurine (26a), (—)-stepharine (27b), the protoberberine (+)-pseudopalmatine (34f), and a series of 2,3,10,11-tetra-substituted tetrahydroprotoberberines (34a-e). Bis-benzyltetrahydroisoquinoline alkaloids appear to be absent from the fruit (413). 

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