Morphine natural opium alkaloids

Natural opium alkaloids codeine phosphate hydromorphone hydrochloride morphine hydrochloride morphine sulfate oxycodone hydrochloride oxymorphone hydrochloride... 

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. 

Opioids are analgesics that work by binding to the opioid receptors found on neurons in various areas of the brain and spinal cord as well as intramural plexuses that regulate the motility of the gastrointestinal and urogenital tracts. Opiates are by definition limited to natural opium alkaloids and their semi-synthetic derivatives. Morphine,... 

Opioids. Morphine [57-27-2] C yH NO, (8) the most prevalent and analgesicaHy potent of the naturally occurring opium alkaloids (qv), has been used as an anesthetic premedication for over one hundred years (93). It has also been used as an iv analgesic for the last four decades, and, since 1969, in high doses as an anesthetic agent (117). 

An alkaloid is a complex organic chemical substance found in plants, which characteristically combines nitrogen with other elements, has a bitter taste, and typically has some toxic, stimulant, analgesic effects. There are many different alkaloids, 30 of which are found in the opium plant. While morphine is the most important alkaloid in opium—for its natural narcotic qualities as well as providing the chemical structure for heroin—another alkaloid, codeine, is also sought after for its medicinal attributes. Other alkaloids include papaverine, narcotine, nicotine, atropine, cocaine, and mescaline. While the concentration of morphine in opium varies depending on where and how the plant is cultivated, it typically ranges from 3 percent to 20 percent. 

The history of the opium alkaloids is too well known to warrant repetition here, but the analgesics based on morphine (l)are too important to be left out of an account of natural products as leads. Thus we shall summarize the clinically more important developments... 

Many alkaloids have pronounced biological properties, and many of the pharmaceutical agents used today are derived from naturally occurring amines. Morphine and related alkaloids from the opium poppy, for instance, are used for pain relief atropine from the flowering plant Atropa belladonna, commonly called the deadly nightshade, is used as an anti-spasmodic agent for the treatment of colitis and ephedrine from the Chinese p smt Ephedra sinica is used as a bronchodilator and decongestant. 

Papaveretnm. Concentrated opium Omnopon Pantopon. A mixture of the hydrochlorides of the opium alkaloids in their approximate natural proportions. Contains approx 50% morphine, 3% oodeine, 20% noscapine, and S% papaverine. Exhibits biological action of morphine and other alkaloids present in opium. Clinical evaluation in intravenous analgesia I. A. Catling et aL, Brit. Med. J. 281, 478 (1980). 

A natural product is a compound synthesized by a plant or an animal. Alkaloids are natural products that contain one or more nitrogen heteroatoms and are found in the leaves, bark, roots, or seeds of plants. Examples include caffeine (found in tea leaves, coffee beans, and cola nuts) and nicotine (found in tobacco leaves). Morphine is an alkaloid obtained from opium, the juice derived from a species of poppy. Morphine is 50 times stronger than aspirin as an analgesic, but it is addictive and suppresses respiration. Heroin is a synthetic compound that is made by acetylating morphine (Section 30.3). 

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... 

Morphine is a naturally occmring alkaloid from the opium poppy seed. Modern formulations employ synthetic morphine. Major and minor sites of morphine activity include spinal and supraspinal opioid receptors. Morphine binds to and activates mu, kappa and delta receptor subtypes. 

As pointed out earlier, the structural diversity of this class of tyrosine-derived secondary metabolites arises from different aryl coupling reactions. The biosynthetic pathway to alkaloids of the protoberberine skeleton, as well as the aporphine and morphine skeleton, is outlined in Scheme 12.4 [14]. While protoberberine [18] and aporphine alkaloids [19-21] are obtained from (S)-reticuline (19), opium alkaloids are biosynthesized from the enantiomeric (/ )-configured natural product (20). 

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