Thebaines, oripavines

The prototypes of rigid opiates all have fused ring structures which may contain three (benzomorphans), four (morphinans), five (morphine) or six (oripavines/thebaines) fused rings. All active opiates in these classes, and in the so-called flexible opiates, exhibit cross tolerance and are reversibly blocked by the opiate antagonist naloxone. 

Analyses of P. orientate from natural habitats showed that the dried latex contained 20% of oripavine (195) and 9% of thebaine (192) (92). Traces of isothebaine (122) were found in plants collected from Khaikhala in northwest Iran. Six different chemotypes of P. orientate were reported (64,93), namely, oripavine, oripavine-thebaine, oripavine-isothebaine, oripavine-aipinigenine, oripavine-thebaine-alpinigenine, and mecambridine-orientalidine-salutari-dine. In all of them, with the exception of one, oripavine was the major alkaloid (82). Feeding experiments in P. orientate with radioactively labeled reticuline and thebaine have demonstrated that oripavine is derived from reticuline and thebaine (93a). Reticuline undergoes racemization in this plant as has been earlier shown for P. somniferum and P. bracteatum. 

Morphine, codeine, oripavine, thebaine Industrial liquors (fiom extraction processes) CD-CZE 100 mM Tris-phosphate (pH 2.8) + 30 mM HP-PCD UV at 214 nm [47]... 

L-Selectride or Super Hydride, 67°, 88-92% yield. Other methods for converting thebaine to oripavine have not been successful. ... 

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. 

N.A. Thebaine, oripavine, morphine, codeine.99-100 Mild sedative to induce sleep in babies, ease cough, relieve pain, narcotic analgesic, antitussive. 

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... 

Oripavine 3-ethyl ether (38), an unnatural analogue of thebaine (35), was found to be metabolized to morphine 3-ethyl ether and to morphine (36). The efficiency of the conversion was comparable to that of natural biosynthesis. (For an examination of other unnatural compounds as substrates for the enzymes of the biosynthesis of morphine alkaloids, see Vol. 4, p. 15.)... 

There are two possible biosynthetic pathways for the conversion of thebaine to morphine, Fig. (67) [148]. One is orthodoxically known in the litreatures [4, 130, 131], that is morphine biosynthesis from thebaine via codeinone and codeine. Another one i.e. the first ever demonstrated by Brochmann-Hanssen in 1984 [149], is the biosynthesis via oripavine and morphinone. The transformed clone could synthesize codeine but lacked morphine though the non-transformed clone obtained from the same plant material accumulated morphine at the latter developmental stage (Table 21). This suppressed morphine content was also observed in the opium derived from the transformed P. somniferum plants that had been... 

Recently the alkaloid oripavine has been shown to have the structure [lxvi] and bears the same relationship to morphine as thebaine does to codeine. On methylation with diazomethane it yields thebaine [96]. 

In 1935 an alkaloid named oripavine having the composition Ci8H2i03N was isolated from Papaver orientale [124] and subsequently from Papaver bracteatum [125], It was shown to contain one —OMe, one —NMo, and one phenolic —OH group [124], and was eventually converted to thebaine [v] by methylation with diazomethane [126] and is in fact 3-0-desmethylthebaine [xxxvn] it bears the same relationship to morphine as thebaine does to codeine. On boiling with... 

Attempts to convert oripavine (the 3-demethylated analogue of thebaine) to an analogue of thebenine failed to give clearly-defined products [26]. 

The oripavines are made from an alkaloid which we have not described so far— thebaine (Fig. 12.26). Thebaine can be extracted from opium along with codeine and... 

Somniferine, O-methylsomniferine, morphine, codeine, papaverine, thebaine, oripavine... 

The opium alkaloid thebaine, although therapeutically useless (causes seizures and has little analgetic action), is important as the chemical starting point for the commercial synthesis of methyldihydromorphinone (Metopon), hydrocodone and hydromorphone, oxy-morphone, and the very interesting oripavine compounds (see later). Since these drugs are modifications of a natural alkaloid, they may be referred to as semisynthetic opiates. 

Alpinigenine (Alkaloid E), bractamine, bracteine [(+ )-orientalinone], braoteoline, coptisine, isothebaine, mecambridine (oreophiline), nuciferine, orientalidine (bractavine), oripavine, oxysanguinarine, papaverrubine B, D, E, protopine, salutaridine, thebaine, and others Alkaloid PO-3, Alkaloid PO-4, Alkaloid PO-5 (alborine. Alkaloid 48,156, 195, 264, 362,... 

Synthesis of thebaine and oripavine from codeine and morphine Barber, Randy B. Rapoport, Henry... 

Kodaira, H. and S. Spector (1988). Transformation of thebaine to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes. Proc. Natl. Acad. Sci. USA 85, 1267-1271. 

Alkaloids Or-1, Or-2, bracteine (= orientalinone), (+)-bracteoline, isothebaine, mecambridine, (-)-orientalinone. oripavtdine, oripavine, papaverrubine C and D, salutaridine, thebaine... 

Recently, Rapoport et al. described a new synthesis of oripavine and thebaine, a practical synthesis of codeine from dihydrothebainone, and the conversion of thebaine to codeine (yield 85% from thebaine) (497, 498). The transformation of thebaine into codeine with sulfonyl hydrazine and later with methyl hypobromite was reported by Krausz (yield 70%) (499) (Scheme 16). 

The quantity of thebaine in P. bracteatum depends on the period of ripening and on the part of the plant. The largest quantity was found in the roots (0.5-1.0%/weight of dry drug) and in the poppy heads (0.23-1.40%) (849). Bohm studied the content of morphinane alkaloids (thebaine, oripavine, and codeine/morphine) in hybrids obtained by hybridization between P. somniferum, P. bracteatum, P. orientale, and P. pseudoorientale and their dependence upon the genetic milieu (847). 

Alkaloids Thebaine, Alpinigenine Oripavine, Isothebaine Isothebaine,... 

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