Oripavine

Oripavine, CigHjiOgN (Item 56 list, p. 173). Tliis alkaloid was isolated by extracting the dried leaves, moistened with ammonia, with ethylene dichloride. It crystallises from alcohol in colourless needles, has m.p. 200-1°, [a]o — 211-8° (CHCI3), yields a hydrochloride, m.p. 244-5°, and a methiodide, m.p. 207-8°. The base is soluble in sodium hydroxide solution, giving a crystalline sodium derivative. It contains one hydroxyl, one methoxyl and one methylimiiio group. 

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. 

RNA gel blot analysis of several members of the genus Papaver demonstrated that salutaridinol 7-O-acetyltransferase transcript accumulated in three-week-old seedlings of P. orientale and P. bracteatum, though not in P. atlanticum or P. nudicaule % P. orientale accumulates the alternate biosynthetic precursor oripavine, and P. bracteatum accumulates the morphine biosynthetic precursor... 

Matta [37] used the conjoining of Aa residues to obtain the properties of the charge distributions of the proteins Leu- and Met-enkephalin that consist of five residues, in a study of the agonistic activity of the oripavine PEO and morphine. Assembly of the five residues with the required terminal groups resulted in net charges of +0.051 e and -0.043 e, respectively. 

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

Salutaridine has been isolated from Glaucium vitellinum,109 Papaver brac-teatum,103 P. lasiothrix,103 and P. pseudo-orientale,103 thebaine103 and its methochloride146 from P. bracteatum, oripavine from P. orientale,103 and... 

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.)... 

Oripavine (= Di-0- Generated via cytochrome P450 anticonvulsant, CNS activity, hallucinogen] O-R agonist (p, k, 8)... 

The authors believe that oripavines such as etorphine and the Sandoz peptide FK 33-824 (a compound active at both sites although with /x-preference) owe the universality of their actions to the presence in their structure of all the critical components required for interaction with both fi- and 5-receptors. 

Energy transfer experiments by spectrofluorimetry enable an estimate to be made of the Tyr-Trp separation in Trp4-Met-enkephalin, an analog that is about a quarter as active as the parent in the MVD test. The value obtained (—10 A) is close to the phenol-phenyl separation in a potent oripavine derivative in support of peptide /3rbend conformations.067 ... 

An NIH group has examined irreversible ligands based on oripavine, etonitazene (p. 387), and fentanyl (p. 287), termed FAO, BIT, and FIT, respectively (see 10). Of these, FIT and FAO proved highly selective alkylators of 5-receptors, while BIT was equally specific toward /x-sites.<34) The N-CPM analog of FAO also had 5-selectivity and displayed the properties of a narcotic antagonist as judged by its effect on the adenylate cyclase activity of hybrid... 

In the case of methadone and its congeners, the dual diphenyl system (CPh2) does not lead to specially elevated potencies, and it is possible that one phenyl ring serves as a steric restraint for the other in achievement of an active conformation. High orders of activity are found in oripavine derivatives without inclusion of extra aromatic elements, but all potent derivatives have extensive additional hydrocarbon elements attached to the morphine skeleton. 

C-14 (or equivalently placed) substituents, as in /3-metazocine and isomorphinan, and the C-6/C-14 ethylene bridge of the potent oripavines. 

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