Isoquinoline alkaloids Erythrina

Isococculidine (= 0-Methylisococculine) (erythrina isoquinoline) Karakoline (= Carmichaeline Karacoline) (norditerpene alkaloid)... 

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. 

The Erythrina alkaloids represent a group of natural products isolated from various species of plants of the same name and found in tropical and sub-tropical regions of the world. They are all spirocyclic isoquinoline alkaloids and found in all parts of... 

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. 

Sharma SK, Chawla HM (1998) Structure Elucidation of Erythrosotidienone and Erythromotidienone - Two New Isoquinoline Alkaloids from Erythrina variegata Flowers. J Indian Chem Soc 75 833... 

Erythrina alkaloids isoquinoline alkaloids, usually tetracyclic, found exclusively in the legume genus Erythrina. 

In many of the isoquinoline alkaloids the tetrahydroisoquinoline skeleton is clearly seen as part of the stmcture, in others it is somewhat obscured, e.g. chelidonine (76) (Sect. 3.4), and in still others, e.g, colchicine (77) (Sect. 4), which is a phen-ethylisoquinoline, and the Erythrina alkaloids (Sect. 3.3) severe modification in the course of biosynthesis has obliterated any suggestion of an isoquinoline moiety. 

Erythrina Alkaloids.—AT-Norprotosinomenine (74) is known to be a key precursor for Erythrina alkaloids (cf. Vol. 8, p. 10 Vol. 9, p. 16 ref. 2), and its unique role compared to isomeric isoquinolines has been confirmed for coccuvine (80) in Cocculus laurifolius.22 The incorporation of JV-norprotosinomenine (74) [the (+)-(S)-isomer is preferred] was with loss of the O-methyl group at C-7 and complete retention of the 4 -0-methyl group, measured relative to a secure internal tritium marker. The results for coccuvine (80) show that no symmetrical intermediate is involved, unlike, e.g., for erythraline. Consequently the same biosynthetic route is not followed. Plausibly this route could be (74) —> (75) — (76) - (77) (Scheme 7). The unsymmetrical intermediate... 

There is no uniform classification for the A. In the literature divisions according to origin (examples Aconitum, Amaryllidaceae, Aspidosperma, cactus, Catharanthus, Cephalotaxus, Cinchona, coca, Corydalis, curare, Dendrobates, ergot, Erythrina, Iboga, Lycopodium, Maytenus, opium, Rauvol-fia, Senecio, Strychnos, tobacco, Vinca alkaloids, salamander, Solanum, Veratrum steroid alkaloids) in addition to divisions according to chemical structure (examples aporphine, benzylisoquinoline, bis-benzylisoquinoline, berberine, carboline, diterpene, inudazole, indole, indolizidine, isoquinoline, lupinane, macrocyclic, morphine, peptide, / -phenyl-ethylamine, piperidine, purine, pyridine, pyrrolidine, pyrrolizidine, quinoline, quinolizidine, quinucli-dine, spermine, spermidine, steroid, terpene, tro-pane, tropolone alkaloids) are used. 

Benzylisoquinollne alkaloids a group of alkaloids found mainly in members of the poppy family (Papaveraceae). The benzyl substituent on Cl of the isoquinoline radical can enter various secondary cycli-zations through phenol oxidation. The ring structures of the medically important Papaveraceae alkaloids (see), Erythrina alkaloids (see) and the fcisbenzyliso-quinoline Curare alkaloids (see) arise in this way. Biosynthetically, papaverine is derived from 2 molecules of dopa, one being converted to dopamine, the other to 3,4-dihydroxyphenylacetaldehyde. Mannich condensation of these two leads first to norlaudano-sine, which is dehydrated to papaverine (Fig. 1). 

A protic-solvent-mediated cycloisomerization of quinoline and isoquinoline propargylic alcohols to give azacycles has found apphcation in the synthesis of the Erythrina alkaloids 3-demethoxyerythratidinone and cocculidine (Scheme 95). ... 

Actually there are no good definitions of alkaloids (Bate-Smith and Swain, 1966) since each one is either too narrow or too broad. Even in the restricted Winterstein and Trier definition, at least five alkaloid families exist that can be derived from different amino acids consequently, there is a need to establish the proper biosynthetic pathways to permit the application of the alkaloid character to chemotaxonomy, It has been mentioned above that canadine (berberidine) may be found in plants of six partially unrelated botanical families. This fact is not surprising when considered in relation to the biochemical investigations of canadine biosynthesis. Many reactions are necessary to convert tyrosine into canadine consequently, one might even wonder why the distribution of this alkaloid is so limited. In contrast, other plants (and even some that produce canadine) can produce many alkaloids that are derived from tyrosine but have a marked difference in structure. Tyrosine serves as the key precursor of alkaloids of the isoquinoline type, but other types of alkaloids, such as colchicine and the Amaryllidaceae and the Erythrina alkaloids, may be synthesized from this amino acid. The nucleus of an alkaloid molecule can arise from different precursors thus the indole nucleus in Erythrina alkaloids arises from tyrosine, while in brucine it comes from tryptophan (Figure 1.5). The alkaloids cinchonamine and cinchonine differ in that cinchonamine has an indole nucleus, while cinchonine (like quinine) has a quinoline nucleus however, they exist in a precursor-product relationship (that is, the quinoline type is derived from the indole type in a one-step reaction). 

The family Annonaceae comprises some 2000 species and only about 150 have been investigated for their chemical constituents. Studies during the past decade have indicated that this family can perform biosynthetic sequences which yield an array of isoquinolines. As examples of the more unique types of isoquinolines, Erythrina alkaloids and the cularines form the subjects of two separate chapters. Relatively little information exists on the pharmacology of the cularines. There are now about 225 bisbenzyl-... 

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