Isoquinoline and related alkaloids

The biochemical importance of secologanin is indicated by the fact that the coupling reaction with tryptamine and dopamine is the first step in the biosynthesis of about 2500 indole, isoquinoline and related alkaloids [2, 7], the most typical of which are shown in Fig. (2). 

The regioselective ET-sensitized addition of primary amines has been cleverly employed by Yasuda and co-woikers in the synthesis of isoquinolines and related alkaloids. For example, the DCNB-sensitized photoamination of stilbene with 2-hy-doxypropylamine in an acetonitrile-water solution yields the adduct 98, which is converted to the benzylisoquinoline 99 upon treatment with CFjSOjH, The P-hydroxyl group of ethano-lamine can be replaced with acetal or vinyl groups which also can serve as precursors of the carbocation required for the acid-catalyzed ring-forming reaction. Analogous reaction sequences have been used to convert phenanthrene to aporphines. ... 

Quinoline, Isoquinoline, and Related Alkaloids 7.9.7 Characterization of Thiazinoquinoiinodione Alkaloids... 

Coutts IGC, Hamblin MR, Tinley EJ (1979) The enzymatic oxidation of phenolic tetrahydroiso-quinoline-1-carboxylic acids. J Chem Soc Perkin Trans 1 2744-2750 Davis VE, Cashaw JL, McMurtrey KD, Ruchirawat S, Nimit Y (1982) Metabolism of tetrahydro-isoquinolines and related alkaloids. In Bloom F, Barchas J, Sandler M, Usdin E (eds) Beta-carbolines and tetrahydroisoquinolines. Liss, New York, p 99 Furuya T, Nakano M, Yoshikawa T (1978) Biotransformation of (RS)-reticuline and morphinan alkaloids by cell cultures of Papaver somniferum. Phytochemistry 17 891-893 Gates M (1953) Conversion of codeinone to codeine. J Am Chem Soc 75 4340-4341 Graves JMH, Smith WK (1967) Transformation of pregnenolone and progesterone by cultured plant cells. Nature (London) 214 124 8-1249... 

In accord with the greater range of menispermaceous genera that are utilized as components of curares, chemical studies have shown that they contain a wide variety of isoquinoline and related alkaloids bis-benzyltetrahydroiso-quinolines, benzyltetrahydroisoquinolines, proaporphines, aporphines, oxo-aporphines, azailuoranthenes, tropoloisoquinolines, and isoquinolobenzaze-... 

The Reissert method15—conversion of an isoquinoline to a 2-benzoyl-1,2-dihydroisoquinaldonitrile (Reissert compound), alkylation, and hydrolysis—has enjoyed wide success in the synthesis of benzyliso-quinoline and related alkaloids.16,17 In particular, aporphines are prepared conveniently by converting isoquinolines to I-(o-nitrobcnzyl)-isoquinolines via a Reissert sequence, followed by A7-alkylation, reduction, and Pschorr cyclization.17... 

Following their syntheses of ( )-pancracine and related alkaloids (vide supra), Hoshino et al [106] had described a different approach involving radical cyclisation of an isoquinoline derivative which permitted a rapid assembly of keto-5,11-methanomorphanthridine skeleton. The syntheses of 413, 414 and 415 commenced with the known 4-hydroxy-6,7-methylenedioxy-1,2,3,4-tetrahydroisoquinoIine (439) (Scheme 62). Subsequent to protection of the amino group as the trifluoroacetyl derivative, the amide alcohol 440 was converted into the amide thioether 441, by reaction with phenylthiol in the presence of zinc iodide. Alkaline hydrolysis of 441,... 

Protoberberine and Related Alkaloids.—The benzylisoquinoline skeleton [as (64)], which appears in diversely modified form in various alkaloids [see, e.g., (66)—(71)], is formed from two molecules of tyrosine label from this amino-acid often appears equally divided over the two halves of the alkaloid examined,1,219 but dopa (60), like dopamine (59), is incorporated only into the isoquinoline moiety cf. Vol. 6, pp. 17, 26 Vol. 7, p. 10 Vol. 9, p. 8). 

Started in the late 1960s, studies on enamide photocyclization and its application to the synthesis of alkaloids have been successfully accumulated and have achieved a number of total syntheses of various types of isoquinoline and indole alkaloids and related heterocyclic compounds (11). 

These hypotheses, although not always correct, have been of inestimable value in guiding tracer experiments on living plants. Experiments on the biosynthesis of berberine and related alkaloids have had, in addition to these guidelines, the benefit of the knowledge gained from previous tracer studies on the biosynthesis of the isoquinoline alkaloids of the papaverine and the morphine series, where it was known that two molecules of the aromatic amino acid, tyrosine, are built into these alkaloids via a pathway involving the intermediacy of norlaudanosoline (XCIV). 

R)-Reticuline (294), one of the most fundamental isoquinoline alkaloids, has been known to be converted into morphine alkaloids by intramolecular oxidative phenolcoupling. Thus, 294 was treated with cytochrome P-450 hnked microsomal Papaver enzyme in a buffer solution (pH 7.5) containing NADPH under aerobic conditions (25 °C, 1 h) to afford in high efficiency and high selectivity salutaridine (295), which was chemically converted to thebaine (296), morphine (297) and related alkaloids. In contrast, the enzyme was not effective in reaction with (5 )-reticuline (Scheme 63). ... 

Sanguinarine (naphto[l,2-c]isoquinoline derivative) and related alkaloids 00CLY15. 

Alpinigenine has been isolated from the dried latex of Papaver bracteatum Rhoeadine, as well as other isoquinoline alkaloids, has been found in the aerial parts of P. fugax of Turkish origin. P. urbanianum has been shown to produce papaverrubine A thin-layer chromatographic procedure on talc has been developed for the separation of papaverrubines A, D, and E from P. rhoeas. Details concerning attempts to correlate results of c.d. studies of rhoeadine and related alkaloids (cf. Vol. 4) with those obtained by the aromatic chirality and... 

In this chapter, ephedrine and related alkaloids, the khat alkaloids (which are related to the ephedrines), and two other types of alkaloids are described. One of them is the naphthalene-isoquinoline alkaloids, which are described in Section 16.3.These alkaloids might also be classified as alkaloids derived from phenylalanine because they possess an isoquinoline skeleton. However, an extra Cj unit has been joined to the carbon to which the nitrogen is attached, as occurs in the case of ephedrine. Therefore, it is considered that the formation of these alkaloids might involve a biosynthetic pathway not utilizing phenylalanine. The other alkaloids are capsaicin and related alkaloids, which are described in Section 16.4. 

There are no reports on the biosynthesis of this type of alkaloid. It is possible that the origin of these alkaloids is phenylalanine, as for other isoquinoline-type alkaloids. However, because this type of alkaloid possesses a methyl moiety attached to the carbon alpha to the nitrogen atom, like ephedrine and related alkaloids, it is also possible that these alkaloids are derived from a C6-Ci unit, such as benzoic acid or benzaldehyde, as in the case of ephedrine and related alkaloids. That is why these alkaloids are included in this chapter. Elucidation of the biosynthetic pathway for these alkaloids is awaited. 

Abstract Protoberberine alkaloids and related compounds represent an important class of molecules and have attracted recent attention for their various pharmacological activities. This chapter deals with the physicochemical properties of several isoquinoline alkaloids (berberine, palmatine and coralyne) and many of their derivatives under various environmental conditions. The interaction of these compounds with polymorphic DNA structures (B-form, Z-form, H -form, protonated form, triple helical form and quadruplex form) and polymorphic RNA structures (A-form, protonated form, triple helical form and quadruplex form) reported by several research groups, employing various analytical techniques such as spectrophotometry, spectrofluorimetry, circular dichro-ism, NMR spectroscopy, viscometry as well as molecular modelling and thermodynamic analysis to elucidate their mode and mechanism of action for structure-activity relationships, are also presented. 

The chemistry of Reissert compounds has been the subject of numerous general reviews (3-10). In 1973 Popp gave a summary on the use of Reissert compounds in the synthesis of isoquinoline alkaloids and related compounds (7). We now wish to summarize new results that have appeared from 1973 to the end of 1985 for the application of Reissert compounds in the synthesis of isoquinoline as well as indole alkaloids. 

The formation of a Reissert anion (intermediate of type 16) is usually the introductory step in a great number of synthetic routes leading to isoquinoline as well as indole alkaloids and related compounds. On the one hand, the alkylation of a Reissert anion with alkyl halide followed by alkaline hydrolysis is the most frequently used method for the synthesis of 1-alkyl- or 1-arylalkylisoquinolines (20) (Scheme 4). On the other hand, Reissert anions react with aldehydes to form... 

Other cation-pseudobase equilibrations that have received detailed spectral investigation include quaternary isoquinoline alkaloids and related isoquinolinium derivatives,910 naphthyridinium mono- and dications,26,38,42 44 50 pyridinium cations,51,52 isobenzopyrylium (isochro-mylium) cations,53 benzothiopyrylium (thiochromylium) cations,40 and 1,3-dithiolium cations.54 PMR spectroscopy has also been useful in the identification of pseudobases as reaction intermediates in several reactions in solution.55-57 While 13C-NMR spectroscopy is also potentially useful for the assignment of pseudobase structure, at present there do not appear to... 

BicucuUme (AA), cryptopine, hydrastine, corlumine, and related isoquinoline alkaloids (AA) securinine harmaline and related (J-carbohne alkaloids (A) muscimol (A) securinine (AA)... 

Ephedrrne and related phenylalkyl amines (AA) reserprne, ihogaine, and related indole alkaloids (AA) cocaine (AA) armonaine and related aporphine alkaloids (AA) arecaidine (AA) norharman and related (J-carholine alkaloids (AA) salsolinol and related isoquinolines (AA)... 

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

Pyridines and isoquinoline undergo reductive Iro/w-oMx -allylation on consequent treatment with triallylborane and alcohol1. Similar reaction of pyrrole leads to a mixture of 2-allyl-3-pyrroline (20%) and mww-2,5-diallylpyrrolidine (60%)1. Certain allylated nitrogen heterocycles thus obtained were used for preparation of alkaloids and related compounds2-3. 

The biosynthesis of the secondary metabolites seems to be related to the differentiation of the cells or plant organs such as shoots or roots [50, 51]. In the section 2, production of isoquinoline alkaloids and tropane alkaloids by adventitious root cultures is described. However, the cultivation of intact plants or their organs is in most cases either phytohormone-dependent or of poor growth, so that these systems are not very useful for industrial purposes [73]. 

The chemistry of Reissert compounds, for example, N-acyldihydroquin-aldonitriles (1) and Af-acyldihydroisoquinaldonitriles (2), was the subject of a review in an earlier volume of this series. The application of Reissert compounds to the synthesis of isoquinoline alkaloids and related compounds... 

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