Morphine alkaloids

Opium alkaloids (morphine, codeine), acetylmorphine, oxyco-deinone, brucine, phenylbutazone, ketazone, trimethazone... 

Apomorphine hydrochloride (44 Apokyn Bertek, 2004), is a semisynthetic derivative of opium alkaloid morphine (43) isolated from poppy (Papaver somniferum), and it has long been known for its erectile activity at the effective dose of 2-6 mg physicians discovered the effect over 100 years ago, but found the drug, at a much higher dose (ca. 200 mg), to be more suitable for poison victims as an emetic because it also causes serious nausea and vomiting. Apomorphine exerts its erectile effect at the central nervous system the drug has been found to be a non-selective dopamine agonist which activates both Di-like and D2-like... 

The most widely used agonists in medical practice are the opium alkaloids morphine and codeine. However, semisynthetic derivatives (hydromorphone, oxymorphone, hydrycodon, oxycodone), whose use is even preferred in certain cases, and strong, purely synthetic compounds (methadone, meperidin, fentanyl, sufentanyl, and others) have found wide use. 

The opium alkaloid morphine is representative for this group of opiates and also for other opioid analgesics. Morphine is a full agonist for both the jx and the k receptors. It is used to relieve severe acute pain, or chronic pain in terminally ill patients. Its oral bioavailability varies from 15% to 35% and its... 

Hydrogenated derivatives of the monocyclic and bicyclic oxazines and thiazines are also very well established compounds and a number are so familiar that they too have trivial names. Tetrahydro-l,4-oxazine, for example, is better known as morpholine, a name first allocated to it because of a supposed, but erroneous, relationship to the alkaloid morphine. By analogy the corresponding thiazine is called thiomorpholine or sometimes thiazane. 

The opium alkaloids morphine, codeine, and thebaine have a phenanthrene nucleus (Figure 11.10 and Figure 11.11). 

Opium alkaloids and derived phenanthrene alkaloids morphine, hydromorphone (Dilaudid), oxymorphone (Numorphan), oxycodone (dihydroxycodeinone, a component of Percodan, Percocet, Roxicodone, Tylox)... 

A total of more than 20 total syntheses have been described which aim to generate the most important members of the morphinan-type alkaloids, morphine and codeine. These long-standing efforts in alkaloid synthesis have been primarily due to the exceptional pharmacological importance of both compounds, as the most efficacious therapies for pain and cough, respectively. 

Overman et al. exercised the CBS reduction strategy during synthesis of the natural opium alkaloid (—)-morphine (50)21 (Scheme 4.3q). Enantioselective reduction of 2-allylcyclohex-2-en-l-one (51) with catecholborane in the presence of the (R)-oxazaborolidinc catalyst (l )-28a provided the corresponding (S)-cyclohexenol 52 in greater than 96% ee. Condensation of this intermediate with phenyl isocyanate, regioselective catalytic dihydroxylation of the terminal double bond, and protection of the resulting diol afforded 53 in 68% overall yield from 51. The ally lie silane 54 for the upcoming iminium ion-ally lsilane cycliza-tion step was obtained in 81% yield by a stereoselective Sn2 displacement of allylic carbamate. 

The opium poppy Papaver somniferum contains two useful analgesic alkaloids, morphine and codeine, as well as thebaine, which not only may be... 

S)-Reticuline is also the precursor for the biosynthesis of benzophenanthri-dine (e.g. sanguinarine, marcarpine), protoberberine, berberine, palmatine) and morphinan alkaloids (morphine, codeine) (see next few paragraphs). 

The alkaloid morphine is isolated from the opium poppy, Papaver somniferum. 

Opium poppy Papaver somniferum L., Papaveraceae) is one of the most important medicinal plants and has been cultivated since early centuries. Opium, the dried cytoplasm of a specialized internal secretory system called the laticifer, is normally collected from the unripe capsule. It is the source for the commercial production of medicinally important alkaloids, morphine, codeine, thebaine, noscapine and papaverine [130, 131], Fig. (61). Morphine, which has strong addictive property, is still the most effective analgesic for the treatment of mortal cancer patients in modem medicine. Codeine is commonly used as an antitussive. However, field cultivation of this plant has been limited since 1953 by the United Nations Opium Conference Protocol to prevent narcotic crimes. Therefore, establishing tissue culture technique for the production of morphinan alkaloids seems to be desirable not only for medicinal purpose but also for decreasing abuse of opiates. 

For the identification of a number of opium alkaloids (morphine, codeine, thebaine, noscapine, papaverine, cryptopine, narceine) and heroin, 3-0-acetylmorphine, 6-0-acetylmorphine and acetyl codeine, Viala et al. 7 made use of three gas chromatographic columns of different polarities (SE-30 3 %, OV-1 2 % and OV-1 2 % plus Igepal 0.2 %).They obtained reliable separation and identification in this way, which was based on the difference in the retention times in the three columns. 

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