Morphinandienone

The synthesis of morphinandienone (22) and aporphine (23) derivatives has been achieved photochemically through irradiation of diazo compound (21) 40) ... 

The anodic oxidation of 1-benzyltetrahy-droisoquinoline derivatives produces morphinandienones according to Scheme 120 [81, 226-233]. 

The solvent may influence the course of such coupling reactions. Thus N-trifluoracetyl-l-benzyltetrahydroisoquinolines (82) cyclize on anodic oxidation in acetonitrile to neospirodienones (83), whereas morphinandienones (84) are formed in methanol-acetonitrile [Eq. (70)].147... 

The use of 2 -nitro or 2 -N-acetylamino substituents leads to cleavage at C-l. The trifluoroacetylation of amino group, however, changed the course of the reaction and the products were not morphinandienones but neospirodienones. This change of the reaction course may be initiated by rearrangement of the intermediate morphin-andienone-type cation. The addition of methanol to the reaction system as a nucleophile, however, makes it possible to trap the intermediate cation before its rearrangement. But the para-para coupling pattern is retained 10). 

The morphinandienone alkaloids themselves can also be electrochemically oxidized. A cyclic voltammogram of morphinandienone (R1, R2 = CH3) 17 in acetonitrile at platinum shows the anodic peaks at 1.15 V and 1.33 V vs. Ag/Ag+. Its preparative anodic oxidation at 1.2 V in CH3CN/0.2 M HBF4 gives trans-10-hydroxy-O-methyl-... 

The borane complex 75 when treated either with BF3OEt2 at room temperature followed by hydrogenation over Pt in methanol or with 1 N NaOH in methanol followed by reduction with sodium borohydride gave the tetrasubstituted dibenzazonine 76 in 75% yield (Scheme 20). This result supports the hypothesized intermediacy of JV-methylneospirinedienones in the acid-catalyzed rearrangement of morphinandienones to dibenzazonines, as in Scheme 16. On the other... 

Morphinandienones have also been synthesized by the oxidation of mono-phenolic benzylisoquinolines with vanadium oxyfluoride in trifluoroacetic acid, other products of the reaction being proaporphines, and similar oxidations have been accomplished with phenethylisoquinolines.183 The same reagent will oxidize the lactam (150) to the dienone (151), which is an analogue of dehydrometatheb-ainone, and the same cyclization may be effected by electrochemical oxidation.184... 

A record number of new aporphine alkaloids, sixteen, has been isolated and characterized during the year under review. Even better methods for the synthesis of aporphines in high yields have been developed,1-3 and an interesting relationship between aporphines, morphinandienones, neoproaporphines, and spirinedienones has been pointed out.1 A novel and unusual alkaloid is eupolauramine (70), which is structurally related to the aristolactams but which incorporates an additional nitrogen atom in ring A.4... 

Floripavidine (9) is a glycosidic aporphine found in Papaver floribundum. Its hydrolysis gives L-rhamnose and N-methylasimilobine.10 The trunk bark of the northern Indian tree Litsea sebifera has yielded the new aporphine litseferine (10) together with the new morphinandienone sebiferine.11... 

Reticuline has been biotransformed into the morphinandienone pallidine, the aporphine isoboldine, and the protoberberines coreximine and scoulerine by rat liver enzyme 37 and the use of isolated enzymes in the formation of natural products, including aporphines, has been reviewed.38... 

Chlorination and bromination of iV-formyl- and N-ethoxycarbonyl-nor-reticuline have been shown to give 8,6 -dihalogenated compounds32 and anodic oxidation of the bridged hexamethylene diether of reticuline has been found to give the proerythradienone (17) and the morphinandienone (18).33... 

W. A. Ayer, Alkaloids (London) 6,252-255 (1976) see also earlier volumes. Morphinandienone alkaloids ... 

The Pschorr reaction(33) has been useful in securing morphinandienones, many of which are difficult to obtain by phenolic oxidation. The f -(-)-2 -aminobenzylisoquinoline (20) was diazotized and the diazonium salt non-catalytically decomposed with heat to salutaridine (19) (Scheme 2.3). 

Other important mammalian benzylisoquinolines which thus far have escaped detection in mammals are (5)-reticuline and its (R) enantiomer TIQ 121b, shown in Fig. 29. The latter compound is required for the biosynthesis of morphinandienones in the opium poppy, and its possible role in biosynthesis of mammalian morphine is discussed in Section IV. 

Exciting new developments have occurred related to the synthesis of aporphines. It has been conclusively shown that VOF3-TFA oxidation of N-formylnorlaudanosine (15) provides in high yield the neospirinedienone (17) via the morphinandienone intermediate (16) which undergoes loss of the original C-6 methyl substituent (Scheme 1)/... 

A parallel reaction also leading to aporphines through the sequence morphinandienone-> neoproaporphineaporphine is the cone. HCl catalysed rearrangement of ( )-0-methylflavinantine (21) to l,2-dihydroxy-9,10-dimethoxyaporphine (22) in a remarkable 98% yield. Catechol 22 was then O-methylated to glaucine (20). Yet another example is the transformation of ( )-O-methylsalutaridine (23) to a mixture of corydine (24) and O-methylcorydine (25) (Scheme 3). ... 

Another interesting finding is that electrolytic oxidation of laudanosine (15b) in TFA affords a 17% yield of glaucine (20) the presumed intermediate again being a morphinandienone. ... 

In view of this demonstrated facile in vitro conversion of morphinandienones to aporphines, there is now a strong possibility that morphinandienones may as well be in vivo precursors of aporphine alkaloids. ... 

For the acid catalysed conversion of the morphinandienone isosalutaridine to a base believed to be 2,10-dimethoxy-3,9-dihydroxyaporphine, see B. Frank, H. I. Lubs, and G. Dunkelmann, Angew. Chem. Intemat. Edn. 1967,6, 969. 

The one and only morphinandienone, (+)-milonine (8,14-Dihydromorphinandienone) (54), was isolated from the dried leaves of Cissampelos sympodialis, a plant used in medicine in northeastern Brazil [50]. Blasko and Cordell reviewed morphinandienone, homomorphinandienone, and other related alkaloids with respect to isolation, structure, elucidation, spectroscopy, and synthesis [94],... 

Recently, we found that TFA treatment in CH2CI2 of o-quinol acetates 66 and 69 derived from 64 and 65 at low temperatures gave the corresponding ( )-morphinandienones 220 and 221 besides ( )-apor-phines 68 and 70 (Scheme 23). The ratio of morphinandienone and aporphine was approximately 1 1 in the reaction of o-quinol acetates 66 and 69 in acetonitrile at -25°C for 5 min (43). 

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