The Aporphines

Oliveridine is the first C-7 methoxylated aporphine isolated. Several A/ -acetylated noraporphines are now known, all of them originating from Liriodendron species.  

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Tuduranine, CjgHjgOgN. This member of the aporphine group (p. 306) is the most recent addition to Sinomenium alkaloids and was isolated by Goto from the mother liquors of sinomenine. It is crystalline, has m.p. 125° (with softening at 105°), and yields a sparingly soluble hydrochloride, m.p. 286° (dec.), [a] f — 148° (dilute MeOH), is freely soluble in alkali, and gives feeble ferric chloride and diazo-colour reactions and a fuchsin-red colour with formaldehyde and sulphuric acid. It behaves as a secondary base and yields a diacetyl derivative, m.p. 170°, [a] / — 321-71° (MeOH), which does not form a methiodide, but can be hydrolysed to A -acetyl-tuduranine, m.p. 277°, — 395-24°, and this can be methylated to... 

Eximidine, Ci,Hj40N(0Me)3. (Item 36 list, p. 172.) A phenolic base, m.p. 133°, yielding a methiodide, m.p. 218° (dec.). It is isomeric with corydine and possibly belongs to the aporphine group (Manske). ... 

It is convenient at this point to deal with the remaining alkaloids of the aporphine group, viz., domesticine, roemerine and the alkaloids of the Anonaceae, Lauraceae and Monimiaceae. 

Berberine is probably the most widely distributed alkaloid. It and the allied alkaloids palmatine, jatrorrhizine, columbamine and coptisine occur somewhat frequently in the Rhcnadales (list, p. 169) as the tetrahydro-derivatives, but, in the botanical families referred to in the distribution list below, the tetrahydro-derivatives are exceptional and the unreduced alkaloids usual. The associated alkaloids include two members of the aporphine group, domesticine and t odomesticine (p. 315), one member of the cryptopine group, y-homochelidonine (p. 294) and two members of the double woquinoline type, viz., berbamine and oxyacanthine (p. 346). 

Scheme 105. Synthesis of the aporphine alkaloids rugosinone (501) and ledecorine (502). Reagents a, MeOH b, NaOH, EtOH c, LAH d, NaBH e, HCHO then NaBH4.

These transformation reactions are similar in part to those previously observed for laudanosine (201) and for the aporphine-benzylisoquinoline alkaloid thalicarpine (202). Laudanosine underwent regiospecific O-demethylation at... 

Recently, a photosensitized synthesis of phenanthrene heterocycles from 1- and 9-(aminoalkyl)phenanthrenes has been achieved109. Irradiation of l-(2-aminoethyl)phen-anthrene and m-DCNB in 9 1 acetonitrile water solution for 2 hours gives 70% of the aporphine 114 and 15% of the dehydroaporphine 115 with 87% conversion of starting material (equation 50). 

The second dimeric base, (—)-pennsylpavoline (179), was shown to correspond to C-l-demethylpennsylpavine. Specifically, its NMR spectrum was devoid of the 8 3.71 singlet which represents the C-1 methoxyl absorption in (—)-pennsylpavine (178). Evaluation of CD spectra of these novel dimers and comparison with those of the aporphine (+)-A -methyllaurotetanine and the pavine (—)-platycerine led to the assignment of the absolute configurations as depicted in expressions 178 and 179. These dimers are probably derived biosynthetically from the aporphine-benzylisoquinoline dimers, (-)-pennsylvanine and (-)-pennsylvanamine, which were found in the same plant (7,173). 

Presented in this section are only such stereoselective intramolecular coupling reactions in which stereocontrol can be exerted. Coupling reactions like the aporphine ring closure of 2,6,7-trialkyl-l-(3,4-dialkylbenzyl)-l,2,3,4-tetrahydroisoquinoline with vanadium(V) oxytriflu-oride to give l,2,6,10,ll-pentaalkyl-5,6,6a,7-tetrahydro-4/F-naphtho[l,2,3-i/]isoquinoline, will not be dealt with in detail1 2,... 

The intramolecular palladium catalyzed ring closure of the tetrahydro-isoquinoline derivative depicted in 8.41. led to the formation of the aporphine derivative in good yield, which was then converted into racemic aporphine in three steps. In the ring closing step 20 mol% palladium acetate and 40 mol% tricyclohexylphosphine were used as catalyst. The removal of the hydroxyl group was also achieved by palladium catalysis through its conversion to triflate and the subsequent reduction with ammonium formate in the presence of palladium acetate and dppf.53... 

A very large number of substituted phenanthrenes have been made from stilbenes by this photocydization method, as have more complex polycyclic aromatic compounds by related reactions involving a single cydizatlon (e.g. 3.64 for chrysenes) or two, or more, successive cydizations le.g. 3.65). The reaction can be nicely adapted to provide a route from 1-benzylidenetetra-hydroisoquinolines to alkaloids of the aporphine family (e.g. 3.66). 

The photocyclization of stilbenes to phenanthrenes has been used in the synthesis of the aporphine ring system347,348 conversion of the... 

This is a 1,1-spirobenzyl intermediate to what is quite likely the entire family of the aporphines. The "pro" part of the name suggests that this is a biosynthetic precursor to these alkaloids. Very often there is a keto function at the 4-position of the benzyl group (equivalent to a hydroxyl group on the original benzyl), to facilitate the spiro loss of aromaticity needed to achieve this type of coupling. This is directly analogous to the (2,4a) attacks needed to get into the morphinans, where... 

A minor constituent of P. somniferum is the aporphine alkaloid isoboldine (Figure 6.58). Other species of poppy, e.g. Papaver orientale and P. pseudoorientale, are known to synthesize aporphine alkaloids as principal constituents rather than morphinan structures. (Aj-Isoboldinc is readily appreciated to be the product of oxidative coupling of (5)-reticuline, coupling ortho to the phenol group in the tetrahydroisoquinoline, and para to the phenol of the benzyl substituent... 

Northalicarpine (498), C40H46N2Og, from Hernandia peltata Meissner, was identified by MS and FT NMR. It is the first nor aporphine-benzylisoquinoline dimer demethylated on the aporphine (rather than the benzylisoquinoline) nitrogen (549). 

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... 

The readily available reagent diphenyl selenoxide has been used as a mild and selective oxidant in the synthesis of aporphines (and homoaporphines). When the benzylisoquinoline (13) was treated with one equivalent of the reagent at room temperature in methanol, and the product was O- methylated with diazomethane, the aporphine (14) was obtained in 80% yield. The alternative use of chloranil, which is a commonly used oxidant for catechols, yielded less than 10% of (14).20... 

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... 

The conversion of reticuline N- oxide into the aporphine corydine under the influence of cuprous chloride has been described in full.28... 

A new biogenetic route to the aporphines has been proposed which does not involve phenolic oxidative coupling, and which proceeds through the intermediacy of protoberberinium salts.6 The alkaloid polycarpine (44) must be derived biogenetically from palmatine (45), and indeed oxidation of (45) in vitro with m-chloroperoxybenzoic acid, followed by hydrolysis, leads to polycarpine (44). Since it is known that photocyclization of simple benzylisoquinoline... 

The aporphine mustard (62) and closely related analogues have shown significant anti-tumour activity.42... 

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... 

The other known alkaloids that have been isolated from S. venosa include (-)-crebanine, dehydrocrebanine, oxocrebanine, oxostepha-nine, liriodenine, (-)-anonaine, (-)-asimilobine, (-)-nuciferoline, (-)-apoglaziovine, (-)-tuduranine, (-)-mecambroline, (-)-stesakine, (-)-ushinsunine, and (-)-4a-hydroxycrebanine. The two major alkaloids found are the known norproaporphine, ( + )-stepharine, and the aporphine (-)-crebanine (28-32). 

Since previous work on the aporphine alkaloids had shown that the absolute configuration may be determined from the sign of their high-amplitude Cotton effect centered at 235-245 nm and that the positive Cotton effect corresponds to (S) configuration of a twisted diphenyl system, the coincidence of the CD curves of (— )-anhydrolycorine methiodide and (+ )-anhydrolycorine methiodide at 240 nm with those... 

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