Aporphine isoquinoline alkaloid

In November 1950,1 studied the effect of bulbocapnine on rats, and published the results in the Archives of Neurology and Psychiatry. Bulbocapnine produces all of the motor manifestations of catatonic schizophrenia in human beings. The drug is an aporphine isoquinoline alkaloid that decreases dopaminergic activity in the brain, and inhibits tyrosine hydroxylase, the rate-limiting enzyme in the catecholamine biosynthesis. 

Tbe aporphines constitute one of the largest groups of isoquinoline alkaloids and have a wide range of physiological activity. For example, bulbocapinine (93) (see Scheme 15) affects the central nervous system and causes catatonia, boldine... 

A useful and timely supplementary listing of new aporphines, oxoaporphines, phenanthrenes, and 4,5-dioxoaporphines has appeared.1 The alkaloids of Glaucium species, which include several aporphines and oxoaporphines, have been tabulated2 and a general discussion of the chemistry and biogenesis of isoquinoline alkaloids, including the aporphines, has been presented.3... 

Hyoscyamine, scopolamine, and other tropane alkaloids (AA) acetylheliosupine and some other pyrrolizidine alkaloids arecoline (A) berbamine, berberine, and other isoquinoline alkaloids dicentrine and other aporphine alkaloids strychnine, brucine cryptolepine (AA) sparteine and other quinolizidine alkaloids (A) pilocarpine (A) emetine himbacine and other piperidine alkaloids (A) imperialine (AA) muscarine (A)... 

Aristolochic acid and related aporphine alkaloids (AA) berbamine and related bis-isoquinoline alkaloids (AA)... 

The Rutaceae are known as a large plant frunUy with approximately ISO genera and 1,000 to 2,000 swedes, chemically characterized by numerous alkaloids of extensive structural diversity. Some isoquinoline alkaloids are known in this family of which especially aporphines, protopines, protoberberines, and benzo[c]phenanthridines are common in the Papave-... 

A two-phase solvent system composed of chloroform-methanol-dilute inorganic acid has been used for the separation of a variety of alkaloids including isoquinoline alkaloids, naphthyl-tetrahydroisoquinoline alkaloids, fla-vonoid alkaloids, pentacyclic aromatic alkaloids, diterpenoid alkaloids, aporphine alkaloids, etc. The following example illustrates a typical systematic solvent selection for the separation of palmatine, berberine, epiberberine, and coptisine from the crude alkaloids of Coptis chinensis Franch by analytical HSCCC. In Fig. 1, nine chromatograms are arranged in such a way that the effects of the concentration of HCl (0.3-0.1 M) and the relative volumes of methanol (4 3 2-4 1.5 2, v/v) on the separation of alkaloids from C. chinensis Franch are each readily observed. As the concentration of HCl is reduced from 0.3 to 0.1 M in the solvent system, the retention time... 

Because benzylisoquinolines have been available synthetically (in racemic form) for decades, there is quite a bit of chemistry known regarding their use as key intermediates in the synthesis of a number of more complex isoquinoline alkaloids. The asymmetric synthesis of benzylisoquinolines has been used to complete total synthesis of representative members of several of these alkaloid classes. As shown in Figure 6, the protoberberine alkaloid norcoralydine, the aporphine alkaloid ocoteine, the isopavine alkaloid reframoline and the morphinan 0-methylflavinantine have been made available in optically active form for the first time (except by isolation or resolution) using this approach. 

Since the mid-1950s, phenol oxidative coupling (7) has been actively applied to the synthesis of many types of alkaloids, with considerable progress being achieved especially in the field of isoquinoline alkaloids (8-H). As to aporphine synthesis, employment of new reagents such as vanadium oxyfluoride (12) greatly improved yields as compared to classical methods such as oxidation with potassium ferricyanide and ferric chloride. 

Ca2+ channels are inhibited by several bis-isoquinoline alkaloids (e.g., berbamine, hernandezine, liensinine, monterine, tetrandine), aporphines (e.g., glaucine, norushinsunine), complex indole alkaloids (bis-nortoxiferine, hirsutine, mitragynine, paspaline, paspalitrem, paxilline, penitrem), or other bulky alkaloids (agelasine, contotoxins, crambescidin, ryanodine). Many channel blocker occur in animal venoms it has been estimated that 10% of marine natural products have these properties [65]. 

Indole and isoquinoline alkaloids continue to play a dominant role. The apor-phinoids, comprising proaporphines, aporphines and related dimers, are treated separately, partly in order to reduce the burden on contributors aristolactams and aristolochic acids, which have not been reviewed since 1961, also are discussed in this chapter. This year the quinolizidine alkaloids, including the sesquiterpenoid Nuphar bases and the appropriate Lythraceae alkaloids, as well as azaphenalenes of plant and insect origin are reviewed together. Amaryllidaceae, Erythrina, imidazole, purine and peptide alkaloids are omitted from this volume, but it is expected that the chemistry of these groups covering the period 1974—1976 will be surveyed in Volume 7. 

One of the most important fields of application of the Pschorr reaction is the synthesis of isoquinoline alkaloids. The syntheses of thalicsimidine [72] (Scheme 46) and aporphine [73] are typical examples. 

More recently, the preparative value of VOCl3 and VOF3-TFA in chemical oxidation has been demonstrated (see Section III, on the pro-aporphine and promorphinane alkaloids) (415,462). Some other authors used the purified enzyme horseradish peroxidase (463). By this method the aporphine base (besides the quaternary dibenzopyrrocoline) is readily obtained from (S)-( + )-laudanosoline hydrobromide or from (/ )-(—)-laudanosoline methiodide with retention of the absolute configuration. The synthesis of 6a,7-dehydroaporphine bases was also carried out by making use of the benzyne reaction (439). Reduction of these substances affords the corresponding aporphine bases (439). The synthesis of isoquinoline alkaloids by lead tetraacetate oxidation was reviewed by Umezawa and Hoshino (343). 

In Ottawa he began a systematic investigation of Fumariaceous plants for their alkaloid content. By developing new methods of separation of the alkaloids he found many new bases of the aporphine, benzophenanthridine, phthalideisoquinoline, protopine, and protoberberine ring systems. Three new classes of isoquinoline alkaloids also owe their discovery to this work. In his examination of Dicentra cucullaria he found the alkaloid cularine, determined its structure, and thereby demonstrated that it belonged to a new ring system. In the same period he isolated many of the alkaloids that are now known as the spirobenzylisoquinolines. Some 25 years later he was... 

Separation of a mixture of secondary and tertiary amines is best accomplished by acetylation followed by trituration with dilute mineral acids. The acid soluble fraction contains the tertiary amine. The secondary amine may be regenerated from its insoluble acetyl derivative by mild acid hydrolysis. Benzoylation, however, cannot be applied with equal impunity for under the conditions for this reaction certain isoquinoline alkaloids (aporphines) suffer ring fission and benzoylation at the nitrogen atom. 

Nozaka, T., R Watanabe, S. Tadaki, et al. 1990. Mutagenicity of isoquinoline alkaloids, especially of the aporphine type. Mutat. Res. 240(4) 267-279. 

Benzyl(tetrahydro)isoquinoline alkaloids. B. a. occur especially in various Annonaceae, Lauraceae, Rhamnaceae, Ranunculaceae, Papaveraceae, and Fa-baceae. They are soluble in ethanol, chloroform, ether and poorly soluble in water. Laudanidine is toxic, it acts as a convulsive and respiratory stimulant, laudan-osine is a tetanic toxin, orientaline is the biosynthetic precursor of isothebaine. Pwtosinomenine occurs especially in Erythrina lithosperma (Fabaceae). Papaverine [ 1 -(3,4-dimethoxybenzyl)-6,7-dimethoxyiso-quinoline] acts as a parasympathicolyticum relaxing smooth musculature, it promotes cerebral perfusion (vasodilatation). It is an antiasthmatic and oral anti-spasmodic agent used in the treatment of gastrointestinal spasms LD50 (mouse i. v.) 25 mg/kg. Reticuline is an important precursor of protoberberines, morphi-nans, aporphines, spirobenzylisoquinolines, and rhoeadine alkaloids. 

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