Oriental poppy

FIGURE 47.1 The oriental poppy (Papaver somniferum) from which opium is derived. The unripe pod from which opium juice is obtained is shown together with the flowering plant. 

The medical use of opium as a pain-relieving drug dates back to the third century. Arab physicians used extracts of the oriental poppy to treat diarrhoea and probably introduced it to the Far East. However, because of its erratic absorption from the gastrointestinal tract, its use as an effective analgesic only became possible with the introduction of the hypodermic syringe in the middle of the last century. 

Opium is obtained from the dried juice from the seed capsule of the oriental poppy, Papaver somniferum. The dried juice contains up to 17% morphine and 4% codeine by weight, as well as other, non-additive alkaloids that lack analgesic activity such as noscapine, papaverine, and thebaine. Papaveretum is a standardized preparation of opium containing 50% morphine. 

During the period of growth of the oriental poppy, Papaver orientale, the plant contains appreciable amounts of thebaine, but during late fall, after ripening and dying of the aerial plant, little, if any, of this alkaloid is to be found, but at this time an optically active base, isomeric with thebaine, may be isolated from the root of the poppy. This base, called isothebaine, was first isolated by Gadamer [1-2] as an unidentified phenolic alkaloid and subsequently examined by Klee [3]. It has also been shown to be present in Papaver bracteatum [4],... 

Thebaine occurs in the oriental poppy during the period of vigorous growth, but during the periods of withering and rest of the plant only isothebaine, believed to be 3 5-dimethoxy-4-hydroxyaporphine (but see Chap. XXIV), can be isolated. The latter could arise from [xvi] by elimination of the elements of water. 

I he seeds of the oriental poppy contain morphine. Morphine is a narcotic that has a variety of effects on the body and the brain, including drowsiness, euphoria, mental confusion, and chronic constipation. Although morphine was first isolated in 1805, not until the 1850s and the advent of the hypodermic was it effectively used as a painkiller. During the American Civil War, morphine was used extensively to reheve the pain of wounds and amputations. It was at this time that the addictive properties were noticed. By the end of the Civil War, over 100,000 soldiers were addicted to morphine. 

Two sets of P. orierUale plants were fed separately, one with doubly labeled orientaline and the other with 3A C-reticuline. The former batch of plants afforded radioactive isothebaine (1.6% incorporation) and negligibly active thebaine (<5xl0 % incorporation) whereas the latter batch gave a reverse result. From these, the thebaine was active (0.2% incorporation) and the isothebaine was virtually inactive (<7x 10" % incorporation). Clearly both alkaloids are being biosynthesized at the time of these experiments and the results show that no significant conversion of isothebaine into thebaine occurs. These experiments also demonstrate that biosynthesis in the oriental poppy is directed to different final skeletons at least in part by O-methylation (39). 

For many centuries morphine and codeine, alkaloids found in the oriental poppy plant, have been used as effective painkillers. Codeine, which is structurally similar to morphine, is used in some prescription painkillers and cough syrups. Heroin, obtained by a chemical modification of morphine, is strongly addicting and is not used medically. The structure of the prescription drug OxyContin (oxycodone) used to relieve severe pain is similar to heroin. Today, there are an increasing number of deaths from OxyContin abuse because its physiological effects are also similar to those of heroin. 

Opium is the dried, powdered sap of the unripe seed pod of Papaver somniferum, a poppy plant indigenous to Asia minor. Theophrastus described its medical properties in the third century BC, but the Sumerians, ca BC 4000, probably perceived its utility. Arab physicians knew of the dmg, and Arab traders carried it to the Orient where it was used as a treatment for dysentery. Paracelsus is credited with repopularizing the dmg in western Europe in the early sixteenth century by formulating opium into "laudanum", which is still in use. More than 20 different alkaloids (qv) of two different classes comprise 25% of the weight of dry opium. The benzylisoquinolines, characterized by papaverine [58-74-2] (1.0%), a smooth muscle relaxant, and noscapine [128-62-1] (6.0%), an antitussive agent, do not have any analgesic effects. The phenanthrenes, the second group, are the more common and include 10% morphine (1, = R = H), 0.5% codeine [76-57-3], C gH2 N03, (1, R = H, R = CH3), and 0.2 thebaine [115-37-7], C 2H2 N03, (2). 

Scheme 13) this may not be the case for aporphines with substituents in positions 1,2,10, and 11 [corytuberine type (25e)]. Because of steric factors these aporphines are more likely to be produced via a dienone proaporphine intermediate followed by a dienone-phenol rearrangement. In the second work, the same authors report that orientaline was detected in the opium poppy by an isotope-dilution method based on its biosynthesis from norlaudanosoline (7p) (258). Administration of labeled orientaline (7s) revealed that in P. somniferum this alkaloid was not a precursor of isoboldine (24c), and the experimental results provided no evidence for a pathway involving norprotosinomenine (7t) this route is, however, very likely for P. orientate and P. bracteatum (Scheme 13). 

Earlier work (in summary, 510) has defined with considerable precision how the 1-benzylisoquinoline system is converted by opium poppies into the morphine group of alkaloids. Norlaudanosoline (7p) was the earliest 1-benzylisoquinoline recognized on this pathway, and it was shown to be built from two aromatic units both derivable from tyrosine one of them was dopamine. The nature of the second unit was unknown. Recently, the studies of P. somniferum, P. orientate, and P. bracteatum have shown (339, 511, 511a) (Scheme 17) that (a) the amino acid (c) can act as a specific precursor of morphine (45c) only one enantiomer of c would be expected to be biologically converted (b) the aromatic nuclei of both building blocks for... 

C7H4O7, Mr 200.10, cryst. Crystals of p. a., a component of the latex of opium poppy, have been known since the 19th century to take up a wide range of molecules during growth from solution. Recently, their ability to accommodate structurally dissimilar dyes and to orient the dye molecules similarly within crystal layers has been demonstrated. This ability is useful for studies examining the anisotropic (orientation-dependent) properties of molecules. 

A minor constituent of P. somniferum is the aporphine alkaloid isoboldine. Other species of poppy, e.g., Papaver orientate and P. pseudoorientale, are known to synthesize aporphine alkaloids as principal constituents rather than morphinan structures. (5)-lsoboldine is readily appreciated to be the product of oxidative coupling of (5)-reticuline, coupling ortho to the phenol group in the tetrahydroisoquinoline and para to the phenol of the benzyl substituent. Some... 

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