Aporphines 7-oxoaporphines

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... 

A complete listing of all naturally occurring aporphines, oxoaporphines, and phenanthrenes is now available and a review on the applications of Pb(OAc)4 to the synthesis of several aporphinoids has appeared. ... 

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 the Philippines, the sap expressed from the stem is drunk to alleviate headache. Using antiplatelet aggregation as a guide to fractionation, Chen et al. isolated a series of aporphines including actinodaphnine, N-methylactinodaphnine, launobine, dicentrine, O-methylbulbocapnine, hernovine, bulbocapnine, and oxoaporphines dicentrinone and liriodenine were isolated from the stems of I. luzonensis (13). 

Alternatively, reduction of the keto-imine (20) with sodium borohydride gave a mixture of two carbinols corresponding to N-demethylated (16) and (17). Irradiation of this mixture produced norushinsunine together with a little noroliveroline. Photolysis of the alcohol (21) gave rise to the oxoaporphine liriodenine (22).21 Synthetic routes to those aporphines that incorporate a hydroxyl group at C-7 that is trans to the proton at C-6a are already known.22 23 A novel synthesis of aporphines via 3-phenylphenethylamines has been developed, and is described in Scheme 1. The aporphine (23) and related species were then synthesized by a modified route.24... 

Glaunine (67) and glaunidine (68) are two new oxoaporphines from Glaucium fimbrilligerum (Papaveraceae).47 Arosine, found in G. flavum Cr. var. vestitum, must be identical with glaunidine, while arosinine, from the same source, possesses structure (69).48 Oxidation of the aporphine corydine with iodine and... 

Photolysis of the hydrochloride of (71) gave the corresponding oxoaporphine O-methylatheroline, in 38% yield, which was converted into the aporphine glau-cine by successive methylation and reduction with zinc in hydrochloric acid.49... 

Oxidation of noraporphines and aporphines with Fremy s salt gives oxoaporphines and oxoaporphinium salts, respectively.75 Aerial oxidation of dehydro-aporphines in the presence of alkali provides the corresponding oxoaporphines, 4,5-dioxoaporphines, and A-methylaristolactams.76 An analysis of the 13C n.m.r. 

Recently, Castedo et al. (137) studied enamide photocyclization for aporphine synthesis and modified Cava s procedure (135 -137) after consideration of the reaction course and structural requirement for the exclusive formation of aporphine. Castedo s group concluded that an enamide should have a forced m-stilbene geometry, in order to avoid an undesired mode of cyclization leading to protoberberine-type compounds and also to avoid a facile conversion to oxoaporphines after cyclization. 

The numbering of the aporphine ring in the following alkaloids (aporphines, dehydroaporphines, oxoaporphines) is according to accepted practice [1,102-106], and is illustrated in the structure of acutifolidine (40). 

Simple isoquinolines are not found in the Menispermaceae of South America. The isoquinolone thalifoline (1) was identified from Abuta pahni [32], Benzyltetrahydroisoquinolines are the biogenetic precursors for aporphines, proaporphines, and oxoaporphines. Yet the only such compound isolated from South American Menispermaceae is (+) coclaurine (2) obtained from Sciadotema eichleriam [52] and Caryomene olivascens [37-38]. The chemistry of simple isoquinolines [65], isoquinolones [66], and benzyltetrahydroisoquinolines [67] have been reviewed. 

The antimicrobial activity of aporphine alkaloids in general has been tested and oxoaporphines were the most active [108]. Some of these alkaloids are found to be toxic for mammalian cells in tissue cultures [109]. In another study of antimicrobial activity of fourteen benzylisoquinoline alkaloids, two oxoaporphines isolated from species of South American Menispermaceae, lysicamine (10) and O-methylmoschatoline (homomoschatoline) (11), had activity against cocci and gram positive bacilli, including Mycobacterium phlei [110]. 

A novel syrTEhesis of the aporphine system has been achieved from the diphenylethylamine (149) by condensation with diethyl oxalate followed by Bischler-Napieralski ring closure to the dihydroisoquinoline (150) and further cyclisation with polyph-osphoric acid to the oxoaporphine (151). A -methylation and reduction of this gave the trimethoxyaporphine 0,iV-dimethyl-tuduranine (M. Grecke and A. Brossi, Helv., 1979, 62. 1549). 

A variety of aporphine, proaporphine, oxoaporphine, and 4,5-dioxo-aporphine alkaloids are known from plants of the families Annonaceae, Lauraceae, and Menispermaceae. 

The numbering system for the oxoaporphines follows that of the aporphines and is shown for liriodenine (1). 

Alternatively, treatment of the aporphine glaucine with a large excess of chromium trioxide-pyridine complex in dichloromethane led in a low yield to a mixture of dehydroglaucine, 1,2,9,10-tetramethoxy-oxoaporphine (6), corunnine (16), and pontevedrine (17) 51). 

Oxidation of the aporphine laureline (i.e., 1,2-methylenedioxy-lO-methoxyaporphine) by chromium trioxide in pyridine generated the yellow 1,2-methylenedioxy-lO-methoxyoxoaporphine (20) [CxaHiiO N-H2O mp 268° (ethyl acetate) (34)]. This material proved to be different from the alkaloid lanuginosine which is l,2-methylenedioxy-9-methoxy-oxoaporphine (5) (34). 

The reagent that had originally been used commonly for the oxidation of aporphines to oxoaporphines was chromium trioxide in pyridine (14-16). A recent study by Cava and co-workers of the oxidation of aporphines and dehydroaporphines has led to the development of superior methods of oxidation which may be summarized as follows (27a). 

It has been pointed out that oxoaporphines are probably formed in nature by the oxidation of aporphines. Substantial support for this hypothesis comes from the fact that in several instances the corresponding aporphine or noraporphine base is found in the same plant... 

The term aporphinoids covers aporphines and their close biogenetic precursors, the proaporphines. Alkaloids derived from relatively straightforward biological transformations of proaporphines or of aporphines are also encompassed, so that proaporphine-benzylisoquinolines, aporphine-benzylisoquinolines, aporphine-pavines, oxoaporphines, dioxoaporphines, aristolactams, and aristolochic acids, as well as phenanthrenes, will be discussed. Azafluoranthenes are also included within the scope of aporphinoids for reasons which will become clear toward the end of the present chapter. 

The unusual alkaloids imeluteine (99) and rufescine (100), found in Abuta imene and A. rufescens, probably originate biogenetically from decarbonylation of oxo-aporphine precursors. Such an in vivo pathway is supported by the observation that Abuta imene also produces the oxoaporphine homomoschatoline (1,2,3-trimethoxyoxoaporphine). It is unlikely, on the other hand, that azafluoranthenes... 

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