Papaver species

With a morphine biosynthetic gene in hand, we believed we could begin to address the question why only P. somniferum produces morphine, while other Papaver species such as P. rhoeas, P. orientale, and P. bracteatum do not. Unexpectedly, we found that the codeinone reductase transcript was present to some degree in all four species investigated. A review of the literature revealed no alkaloids reported in P. rhoeas for which codeinone reductase should participate in the synthesis. Similarly, P. orientale accumulates the alternate morphine biosynthetic precursor oripavine, but codeinone reductase is not involved in the biosynthesis of oripavine, acting instead after this alkaloid along the biosynthetic pathway to morphine.22 P. bracteatum produces the morphine precursor thebaine as a major alkaloid. As for oripavine in P. orientale, codeinone reductase would act in P. bracteatum after thebaine formation on the pathway to morphine. It appears, therefore, that the reason that P. rhoeas, P. orientale, and P. bracteatum do not produce morphine is not related to the absence of the transcript of the morphine biosynthesis-specific gene codeinone reductase. The expression of codeinone reductase may simply be an evolutionary remnant in these species. 

The presence of pavines and isopavines has been used to provide assistance for taxonomic classifications, and to determine intergeneric and phylogenic relationships in the genera Papaver and Argemone. The results of extensive chemical research on Papaver species demonstrated that morphologically distinct sections are also chemically distinguishable by virtue of their alkaloidal profile (170). Out of nine well-defined sections of Papaver, the Section Scapiflora, which displays... 

It has been suggested that the presence of (—)-amurensinine (25) as the main alkaloid in various Meconopsis species indicates the relationship of this genus with Papaver species of the Section Scapiflora 80). By way of parallel thinking, the genus Roemeria, which is known to produce isopavine bases, can be interrelated with the Papaver species of the Section Scapiflora as well as with Meconopsis species. 

Papaver Alkaloids.—Biosynthesis of morphine (36) occurs, in Papaver somniferum, through reticuline (33) by way of thebaine (35). The sequence from (35) to (36) involves, inter alia, two O-demethylations, with that at the methoxy-group at C-6 occurring first.1,2 Confirmation that the other methoxy-group is not demethylated first in this Papaver species obtains from the failure to detect oripavine (37), which is found in other Papaver species, as a natural constituent of P. somniferum. The experiment involved attempted isolation of radioactive (37), using inactive alkaloid as carrier, following a feeding experiment with radioactive reticuline (33).37... 

Ziegler, J. Voegtlander, S., Schmidt, J., Kramell, R., Miersch, O., Ammer, C., Gesell, A. and Kutchan, T.M. (2006) Comparative transcript and alkaloid profiling in Papaver species identifies a short chain dehydrogenase/reductase involved in morphine biosynthesis. Plant.., 48,177-92. 

Ziegler J, Diaz-Chavez ML, Kramell R, Ammer C, Kutchan TM. Comparative macroarray analysis of morphine containing Papaver somniferum and eight morphine free Papaver species identifies an O- methyltransferase involved in benzylisoquinoline 40. biosynthesis. Planta 2005 222 458-471. 

Quinoline alkaloids of Turkish Papaver species 02PAC557. 

P. somniferum andP. setigerum (Section Mecones). It follows that not all Papaver species are capable of demethylating and hydrogenating thebaine to codeine and morphine. 

Papaver Alkaloids.—It is well established that the 1-benzylisoquinoline skeleton [as (70)] found in the alkaloids of Papaver species, amongst many others, arises from two molecules of tyrosine, with dopamine serving as an intermediate for one half of the skeleton (see Scheme 11). In spite of the extensive and fruitful studies on H. Rosenberg and S. J. Stohs, Phytochemistry, 1974,13,1861. 

Production of Alkaloids by Cell Cultures of Papaver Species ... 

In conclusion, undifferentiated cell cultures of Papaver species do not produce morphinan alkaloids. On differentiation laticifers are formed this is probably an important factor for the production of morphinan alkaloids, but other, still unidentified, factors also play a role. On the other hand, differentiation is not necessary for the production of sanguinarine (see Section VI,F). 

Papaver species. The P. a. are soluble in hot acetone and readily soluble in chloroform. 

Mecambrine C, H,7N03 295.34 178.5- 179.5 -116 (CHCI3) Meconopsis cambrica, Papaver species 1093-07-8... 

Muramine C22H27NO5 385.46 176-177 Papaver nudicaule and Papaver species, Glaucium viteliinum, Argemone munita, A. squarrosa 2292-20-8... 

Norreticuline is not a precursor for papaverine. The problem of the ease of A -demethylation in Papaver species is still not completely solved since labeled ( )-reticuline was not incorporated in papaverine while (+)-laudanosoline, which possesses the same absolute configuration as (—)-nor-laudanosoline, was incorporated. It is known that in some cases iV-demethyla-tion definitely does occur since morphine is metabolized to normorphine. ... 

In modem medicine, mily the purified opium alkaloids and their derivatives are commonly employed. Although the ripe poppy capsule can contain up to 0.5 % total alkaloids, opium represents a much concentrated form and up to 25 % of its mass is composed of alkaloids. Of the many (>40) alkaloids identified, some six represent almost all of the total alkaloid content. Actual amounts vary widely, e.g., morphine (4-21 %), codeine (0.8-2.5 %), thebaine (0.5-2.0 %), papaverine (0.5-2.5 %), noscapine (narcotine) (4—8 %), and narceine (0.1-2 %). A t3q>ical commercial sample of opium would probably have a morphine content of about 12 %. Powdered opium is standardized to contain 10 % of anhydrous morphine, usually by dilution with an approved diluent, e.g., lactose or cocoa husk powder. The alkaloids are largely combined in salt form with meconic acid, opium containing some 3-5 % of this material. Meconic acid is invariably found in opium but, apart from its presence in other Papaver species, has not been detected elsewhere. It gives a deep red-colored complex with ferric chloride, and this has thus been used as a rapid and reasonably specific test for opium. Of the main opium alkaloids, only morphine and narceine display acidic properties, as well as the basic properties due to the tertiary amine. Narceine has a carboxylic acid function, while morphine is acidic due to its phenolic hydroxyl. This acidity can be exploited for the preferential extraction of these alkaloids (principally morphine) from an organic solvent by partitioning with aqueous base (Table 15.6). 

It is because, in the event, secondary metabolites derive from but a handful of primary metabolites along pathways involving generally the simplest reactions in organic chemistry and little rearrangement, that speculation about their biosynthesis can be so accurate. Also invaluable in this regard, is the identification of metabolites of similar structure in the same, or related, species. Thus benzyl-isoquinoline alkaloids [as (2.7)] and morphine (2.2) are both found in Papaver species. It follows reasonably that morphine derives from a compound type of (2.7) (Section 6.3.4). 

TABLE I. Possibilities for synthetical heroin manufacture from Papaver species... 

Meconopsis comprises some 40 species which are mainly indigenous to China and the Himalayas. Protopine (3), protoberberine (5), benzophenanthridine (6), isopavine (13) and aporphine alkaloids (Fig. 2) have been isolated from a small number of species. Rhoeadine alkaloids, which are present in Papaver species, also occur in Meconopsis and their distribution appears to be limited to these two genera (Slavik and Slavikova 1977). The sole European representative, M. cambrica growing in England produces magnoflorine (4) as the major alkaloid, together with protoberberine (5), proaporphine (14) and promorphinan alkaloids (15) (Hemingway et al. 1981). 

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