Morphinan isoquinoline alkaloids morphine

Strychnos usambarensis (Loganiaceae) [root] S. Am. Indian poison curare component Derived synthetically from morphine, a morphinan isoquinoline alkaloid from Papaver somniferum (opium poppy) (Papaveraceae) [aerial]... 

Somewhat more effective catalysts are obtained by replacing BINAP with TolBINAP, which is 2,2 -bis(di-p-tolylphosphino)-l,l -binaphthyl.4 The presently preferred catalysts are complexes of Ru(OCOCF3)2 with (R)- or (S)-TolBINAP, obtained by treatment of Ru(OAc)2TolBINAP with 2 equiv. of trifluoroacetic acid. Such catalysts promote hydrogenation of typical enamides in 98% ee and 98% yield. This reaction can be used to provide asymmetric synthesis of isoquinoline alkaloids as well as of morphinans used as substitutes for morphine. 

The role of reticuline as an intermediate in the biosynthesis of the mor-phinan alkaloids (Fig. 2.8) was demonstrated by the isolation both of (S)-and (f )-reticuline from the opium poppy. An excess of the (S)-reticuline over the (f )-isomer was found in opium (poppy latex) obtained from the mature plant, in contrast to the roughly equal amounts of these two isomers that occur in poppy seedlings. Both isomers were found to be incorporated into morphine, the major alkaloid isolated from opium, although incorporation of the (f )-isomer was slightly more efficient. (f )-Reticuline is firmly established in P. somniferum as the precursor of the morphinan-type alkaloids (Loefer and Zenk, 1990). (S)-Reticuline, however, is the central intermediate in isoquinoline alkaloid biosynthesis. It has been postulated that (R)-reticuline is formed from (S)-reticuline by isomerization. This inversion of configuration can be explained by the intermediate formation of the 1,2-dehydroreticulinium ion originating from (S)-reticuline, followed by stereospecific reduction to yield the (R) counterpart. The 1,2-dehydroreticulinium ion is efficiently incorporated into opium alkaloids and its role as a precursor of the morphinan-t)q)e alkaloids has been unequivocally established (De-Eknamkul and Zenk, 1990, 1992). 

Opitim contains 10-25% alkaloids, and the main constituent is morphine. Other than morphine, more than 25 alkaloids are known, and among them are other morphinan-type alkaloids (codeine and thebaine), benzyl-isoquinoline-type alkaloids (papaverine and noscapine), and protopine-type alkaloids (protopine). The biosynthetic precursor of all of these alkaloids is phenylalanine. 

Morphinan alkaloids are the pharmaceutically most important class of isoquinoline alkaloids. Codeine and morphine are found only in Papaver somniferwn and closely related species. Both alkaloids are derived from (R)-reticuline, the absolute stereochemistry of which corresponds with the configuration of morphinan alkaloids. Re-ticuline is therefore an important branch point in isoquinoline bio nthesis. However, either enantiomer of reticulme, when fed separately, is incorporated into morphinan alkaloids essentially to the same extent. The question therefore arises by which mechanism (R)-reticuline is formed within the plant. 

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