Morphinandienones aporphines

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... 

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

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... 

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). ... 

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. ... 

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). 

Some years ago a general synthetic method 52) for the morphinan-dienone-type alkaloids was discovered by modifying the Pschorr reaction which had been used widely for the synthesis of the aporphine alkaloids and this method was applied to a synthesis of the homo-morphinandienone-type compounds. 

Acid-catalysed rearrangement of the quinol ether (91), itself obtained by phenolic oxidative coupling, unexpectedly gave an aporphine which on O-methylation afforded 1,9,10-trimethoxyaporphine (92). Ferricyanide oxidation of reticuline supplied isoboldine and the morphinandienone pallidine. ... 

The conversion of reticuline (41) into protoberberine alkaloids (coreximine and scoulerine), a morphinandienone alkaloid (pallidine), and an aporphine alkaloid (isoboldine) by rat-liver enzyme has been reported. ... 

Since morphinandienones were postulated as intermediates in these transformations, it was only fitting that their acid-catalyzed rearrangement also be investigated. Indeed, it was established that they too lead to aporphines via neoproaporphines as shown below in the case of (9-methylflavinantine (18), the catalyst being concentrated hydrochloric acid. ... 

In view of Kupchan s in vitro synthesis of aporphines via the rearrangement of morphinandienones, it is rational to conceive of a Battersby-Kupchan... 

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