Annonaceae benzylisoquinolines

Whereas the Annonaceae are characterized primarily by benzylisoquinoline alkaloids, two pyrrolidine alkaloids have recently been found in species belonging to this family. Squamolone (29) was isolated from Annona squamosa L. by Chinese workers in 1962 (68). Despite careful spectroscopic investigation and a total synthesis (Eq. 1), squamolone was assigned the incorrect diazepine formula 30. The correct structural formula (29) was later established by an unambiguous synthesis of 30 (Eq. 2). Compounds 29 and 30 proved to have very similar spectroscopic properties, which could justify the early confusion (69). 

Benzylisoquinolines, of which more than 2500 structures are known, are found as defence chemicals within the families of the superorder Mag-noliids (comprising Piperales, Laurales and Magnoliales with the families Annonaceae, Eupomatiaceae, Aristolochiaceae, Magnoliaceae, Lau-raceae, Monimiaceae), Nelumbonaceae and Ranunculales (i.e. Berberidaceae,... 

The protoberberines constitute a group of alkaloids that can theoretically be derived from benzylisoquinolines by condensation with S-adenosyl-methionine. Protoberberine alkaloids occur in a wide variety of plant families, including the Annonaceae, Berberidaceae, Menispermaceae, Papa-veraceae, Ranunculaceae, and Rutaceae. Investigation of the stem of Anamirta cocculus (L.) Wight and Arn. (Menispermaceae), a southeast Asian plant collected in Sri Lanka, has afforded two protoberberine alkaloids, (-)-8-oxotetrahydropalmatine (62) and oxypalmatine (63) (46), whereas the stems and roots of the same species occurring in Indonesia have yielded, in addition to 62, berberine, palmatine, magnoflorine, and columbamine (58). 

No biogenetic details of simple isoquinolone were elucidated, but it is likely to yield the isoquinolones from the oxidation of benzylisoquinolines. There are a few isoquinolones in the Annonaceae. Only three simple isoquinolones, doryphomine (A-7), cherianoine (A-8) and thalifoline (A-9), were isolated from the stems of A cherimola [14,15]. 

Monomeric benzylisoquinolines do not appear to have potential. The activity of some aporhinoids, like isoguattouredigine (111) (from Guatteria foliosa, Annonaceae) argentinine (112), unonopsine (113) and hydroxynomuciferine (114) show only minor activity against T. cruzi in vitro (EC50 250 fiM) [130, 131]. 

Thornber compared the presence of 11 benzylisoquinoline alkaloids in the plants of the Papaveraceae, Menispermaceae, Berberidaceae, Magnol-iaceae, Ranunculaceae, Tutaceae, Monimiaceae, Annonaceae, Aristolo-chiaceae, Lauraceae, and Nymphaceae, and he concluded that the alkaloids cularine and morphine (including codeine and thebaine) are present only in the genera Corydalis and Dicentra (alkaloid cularine) and in the genus Papaver (morphinane alkaloids) the hasubanonine and bisben-zylisoquinoline alkaloids do not occur in Papaver plants (838). 

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. 

The simplest derivatives of the tetrahydrobenzylisoquinoline alkaloids are the aporphine alkaloids (Fig. 32.12). Aporphine alkaloids (about 650) are widespread and occur in almost the same families as benzylisoquinoline alkaloids (Guinaudeau and Bruneton, 1993 Kametani and Honda, 1985). Several subgroups of aporphine alkaloids are known [noraporphines, dehydroaporphines (34), oxoaporphines (35), dimeric apor-phines, and phenanthrenes (36)] (Fig. 32.13) (Cave et al., 1987). The aporphine alkaloids present in members of the Annonaceae and in the genus Thalictrum (Ranunculaceae) have been reviewed (Cave et al., 1987 Schiff, 1987). 

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. 

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