Papaver somniferum transformation

Biotransformations of morphinan alkaloids have been reported for plant, fungal, and mammalian enzymatic systems with emphasis on rather specific reactions such as the reduction of ketones, N- and O-demethylation, and perox-idative transformations. Furuya et al. used immobilized tissue culture cells of Papaver somniferum to accomplish the selective reduction of codeinone (135) to codeine (136) (207) (Scheme 30). Suspension cultures of a well-established cell line of P. somniferum were grown for one week as a source of cell mass for immobilization in calcium alginate. The cells continued to live in the alginate matrix for 6 months maintaining their biological activity. The reduction of co-... 

Semi-Synthetic Transformations of the Morphine Alkaloids Although it has been synthesised (ref 61), (now by four distinct routes) morphine (63), a powerful analgesic is readily available from the natural source, opium obtained from Papaver somniferum as the major alkaloid present (approx. 10%) and indeed the first to be isolated by Serturner in 1803, while the methyl ether, codeine (64) which comprises only 0.5% is relatively weakly active. Thebaine (65) a third component of opium is non-analgesic but is important as an intermediate for the formation of codeine, a somewhat scarce commodity (ref. 62) but a valuable mild analgesic and anti-tussive in great demand. It is best prepared from morphine by methylation with phenyl trimethylammonium ethoxide the by-product consisting of dimethylaniline (ref.63). 

Transformation of Papaver somniferum L. and enhanced production of isoquinoline alkaloids... 

Figure 4. Regioselective Oxidative Coupling The final step for the completion of the pentacyclic ring system of the morphine alkaloids involves the closure of the C4-C5 ether bridge. Synthetic salutaridine has been transformed in vivo to thebaine, codeine, and morphine in Papaver sominiferum. Reduction of the dienone was proposed,30 and indeed, hydride reduction of salutaridine produces a mixture of two epimeric alcohols. However, upon feeding 7-3H labelled salutaridinol epimers to Papaver somniferum, only the S-isomer was converted into thebaine an indication that the reaction is enzyme mediated.31 >32 This finding contradicted earlier work by Barton in which the configuration of the alcohol was assigned as R (See description of Barton s synthesis, ref. 50).

Park SU, Facchini PJ. Agrobacterium rhizogenes-mediated transformation of opium poppy, Papaver somniferum L., and California poppy, Eschscholzia cahfomica Cham., root cultures. J Exp Bot 2000 51(347) 1005-16. 

Yoshimatsu K, Shimomura K (1992) Transformation of opium poppy (Papaver somniferum) with Agrobacterium rhizogenes MAFF03-01724. Plant Cell Rep 11 132-136... 

Frick, S. et al. (2004) Transformation of opium poppy (Papaver somniferum L.) with antisense berberine bridge enzyme gene (anti-bbe) via somatic embryogenesis results in an altered ratio of alkaloids in latex but not in roots. Transgenic Res. 13, 607-613... 

Brochmann-Hanssen E, Chen CH, Chen CR, Chiang HC (1975) Opium alkaloids, part XVI. The biosynthesis of 1-benzylisoquinolines in Papaver somniferum. Preferred and secondary pathways stereochemical aspects. J Chem Soc Perkin Trans 1 1931-1937 Brochmann-Hanssen E, Cheng CY, Chiang HC (1982) Biosynthesis of opium alkaloids The effects of structural modification of reticuline on racemization and bio transformation. J Nat Prod 45 629-634... 

Coutts IGC, Hamblin MR, Tinley EJ (1979) The enzymatic oxidation of phenolic tetrahydroiso-quinoline-1-carboxylic acids. J Chem Soc Perkin Trans 1 2744-2750 Davis VE, Cashaw JL, McMurtrey KD, Ruchirawat S, Nimit Y (1982) Metabolism of tetrahydro-isoquinolines and related alkaloids. In Bloom F, Barchas J, Sandler M, Usdin E (eds) Beta-carbolines and tetrahydroisoquinolines. Liss, New York, p 99 Furuya T, Nakano M, Yoshikawa T (1978) Biotransformation of (RS)-reticuline and morphinan alkaloids by cell cultures of Papaver somniferum. Phytochemistry 17 891-893 Gates M (1953) Conversion of codeinone to codeine. J Am Chem Soc 75 4340-4341 Graves JMH, Smith WK (1967) Transformation of pregnenolone and progesterone by cultured plant cells. Nature (London) 214 124 8-1249... 

Aberrant Biosynthesis of Unnatural Alkaloids.—Kirby S has demonstrated that the opium poppy Papaver somniferum) is capable of carrying out transformations of unnatural precursors to unnatural alkaloids. The 0natural conversion of codeine into morphine by feeding to the plant a mixture of a [2- H]codeine derivative and [N-methyl- C]codeine. One unnatural transformation which was more efficient than the natural one was the conversion of dihydrodeoxycoddne (10) into di-hydrodeoxymorphine (11) (Scheme 4). Kirby concluded that neither the 6-hydroxy-group nor the 7,8-double bond in codeine is important for binding to the enzyme responsible for demethylation of the 3-methoxy-group of codeine. 

Details of the transformation of thebaine to morphine (Scheme 5) have been worked out by studying the metabolism of potential intermediates in Papaver somniferum. The results obtained (see Table under P. somniferum) are consistent with the sequence thebaine- neopinone- codeinone->codeine->mor-phine. 

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