Annonaceae isoquinoline alkaloids

Semi-synthetic from Morphine (morphinan isoquinoline alkaloid from Papaver somniferum, opium poppy) (Papaveraceae) [aerial] Desmos (Annonaceae), Laurelia (Atherospermataceae), Litsea, Sassafras (Lauraceae), Liriodendron (Magnoliaceae), Boldea, Peumtis, Monimia (Monimiaceae), Retanilla (Rhamnaceae) spp. 

Isoquinoline alkaloids are the second major class of alkaloids encountered in Sri Lankan flora and occur mainly in the families Annonaceae, Berberidaceae, Fabaceae, Lauraceae, and Menispermaceae. Plants of the Annonaceae have... 

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. 

Protoberberine alkaloids. Most P. a. occur as tetra-hydroprotoberberines or as protoberberinium salts. The P. a. are among the most widely distributed group of the isoquinoline alkaloids, they occur in at least 9 plant families, especially in Annonaceae, Berberida-ceae, Lauraceae, Menispermaceae, Papaveraceae, and Rutaceae, as well as in Fumariaceae (see table). 

Other families known to possess isoquinoline alkaloids include the Alangiaceae, Chenopodiaceae (a family related to the Cactaceae), Fabaceae, Musaceae, Nymphaeaceae, and Sterculiaceae (Lundstrom, 1983). At least four species of the Chenopodiaceae contain isoquinoline alkaloids, whereas other species contain P-phenylethylamines. Many of the plants that contain benzylisoquinoline alkaloids also contain smaller amounts of isoquinoline alkaloids. Among these are plants belonging to the Annonaceae, Euphorbiaceae, Fuma-riaceae, Hemandiaceae, Menispermaceae, Monimiaceae, Papaveraceae, Ranunculaceae, and Rhamnaceae (Lundstrom, 1983). The distribution of benzylisoquinoline alkaloids is discussed in more detail below. 

Isoquinoline alkaloids are formed by the reaction of phenylethylamine and glyoxylic acid and subsequent decarboxylation, followed by cychzation. In the Annonaceae, only 18 representatives were found. Salsobnol (1.18), a simple tetrahydroisoquinohne, was reported in Annona reticulata together... 

ReticuIine has been found in many plants of the families of Annonaceae, Hernandiaceae, Lauraceae, Monimiaceae, Papveraceae, and others. This alkaloid is known to serve as an important intermediate in the biosynthesis of more complicated isoquinoline alkaloids. 

From the benzylisoquinolines are derived all the types of isoquinoline alkaloids found in the Annonaceae (Fig. 3) berberines, aporphines, oxoaporphines, phenanthrenes, cularines, morphinanedienones, isoquinolones, dimethylaminoethyl-benziles and bisbenzylisoquinolines. 

In this review I will not catalogue all the isoquinoline alkaloids which have been found in the Annonaceae, but instead will choose some examples of recent studies, particularly from my own laboratory. 

Isoquinoline and isoquinoline derived alkaloids are mainly distributed in the families Annonaceae, Lauraceae and Menispermaceae. 

The aporphine alkaloids constitute a large subgroup of alkaloids derived from isoquinoline and are widely distributed especially in the Annonaceae, Lauraceae, Magnoliaceae and Menispermaceae. 

The known chemistry of the Annonaceae is mainly based on the work of Cave and Leboeuf on the benzyhsoquinoline alkaloids. After this work, several papers were published which evidenced the presence of alkaloids derivatives of isoquinolines. Approximately 800 alkaloids of the types isoquinolines, protoberberine, aporphine, and others were isolated from different genera of the Aimonaceae. Previous chemical and pharmacological investigations have indicated that bisbenzylisoquinolines are important bioactive components existing in plants of the Annonaceae family. Other terpenes, flavonoids, Hgnans, acetogenins, and some aromatic compounds are also found in the family but the alkaloids are the major chemical constituents. 

This type of alkaloid is new, not only in the Annonaceae, but in the plant kingdom. Although about 20 bisbenzylisoquinoline alkaloids have been described so far with a biphenyl bond joining their benzyl rings, all of them also possess one or two diaryl ether bridges between their isoquinoline moieties. 

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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