Morphinandienone synthesis

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

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... 

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)/... 

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],... 

Bischler-Napieralski and Pictet Spengler reactions continue to serve well for benzylisoquinoline syntheses.76,77 In the latter reaction, use of a-formylphenyl-acetic esters for the non-nitrogen-containing component appears to be advantageous.77 An interesting sequence of reactions (43)—>—>(44) (Scheme 4) has apparently been applied to the synthesis of papaverine [44 R = 3,4-(MeO)2-C6H3CH2 ] and related alkaloids.78 An attempt to convert ( )-reticuline (37 R = H) into a morphinandienone-type alkaloid by enzymic oxidation with... 

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. 

Morphines and Morphinandienones.—Reviews on the alkaloids of the genus Papaver and the family Papaveraceae have appeared, and a recent detailed review of the morphine alkaloids is now available. Reviews on the synthesis of morphinandienone alkaloids have also been published. ... 

A short and efficient synthesis of a morphinandienone involves the electrolysis of the non-phenolic laudanosine (204) at a platinum electrode, to afford a 52% yield of 0-methylflavinantine (205) (Scheme 12). ... 

Development and application of new oxidation systems utilizing oxome-talate catalysts, particularly in direct C—H functionalizations of aromatic compounds and in synthesis of morphinandienone alkaloids 12CPB799. 

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

Miller LL, Stewart RF (1978) Synthesis of morphinandienones, a dihydrophenanthrone, and pummerer s ketemes by anoelic coupling. J Org Chem 43 1580-1586... 

Morphinandienones, recognized as intermediates in the biosynthesis of opium alkaloids (Barton et al. 1965), were obtained in vitro by processes mimicking the plant synthesis (Schwartz and Mami 1975, Szantay et al. 1982, White et al. 1983). When N-formylnorreticuline (39) (Rj = CHO, R2 = H) was brominated at C-6 to (39)... 

Initial investigations in opiate total synthesis at NIH focused on the biomimetic route, shown above and recently studied extensively by Szantay et al. (1983) and Schwartz and Zoda (1981) in which a reticuline derivative (11) is oxidatively cyclized to a salutaridine derivative (12) which would be convertible to thebaine and hence to codeine and morphine. Traditionally, this approach has been complicated by control of the product distribution ratio and the tendency of the desired morphinandienones to undergo secondary transformations. An effective synthesis of reticuline derivatives (Rice and Brossi 1980) was developed as a prerequisite to this approach at NIH, and a simple synthesis of racemic and chiral pavinans and isopavinans (Rice et al. 1980) resulted from these studies, but attempts at development of an oxidative cyclization which would be useful for large scale synthesis were unsuccessful. 

---