Phenanthrene alkaloid

Chemical Class-. Natural opium alkaloid phenanthrene derivative... 

Brand Name(s) Astramorph PF, Avinza, DepoDur, Duramorph PF, Infumorph, Kadian, M-Eslon, MS Contin, MSIR, MS/S, Oramorph SR, Rapi-Ject, RMS, Roxanol, Roxanol-T Chemical Class Natural opium alkaloid phenanthrene derivative... 

Opium is the dried, powdered sap of the unripe seed pod of Papaver somniferum, a poppy plant indigenous to Asia minor. Theophrastus described its medical properties in the third century BC, but the Sumerians, ca BC 4000, probably perceived its utility. Arab physicians knew of the dmg, and Arab traders carried it to the Orient where it was used as a treatment for dysentery. Paracelsus is credited with repopularizing the dmg in western Europe in the early sixteenth century by formulating opium into "laudanum", which is still in use. More than 20 different alkaloids (qv) of two different classes comprise 25% of the weight of dry opium. The benzylisoquinolines, characterized by papaverine [58-74-2] (1.0%), a smooth muscle relaxant, and noscapine [128-62-1] (6.0%), an antitussive agent, do not have any analgesic effects. The phenanthrenes, the second group, are the more common and include 10% morphine (1, = R = H), 0.5% codeine [76-57-3], C gH2 N03, (1, R = H, R = CH3), and 0.2 thebaine [115-37-7], C 2H2 N03, (2). 

Noscapine [128-62-1] (45) is the second most abundant alkaloid found in opium. Unlike most opium alkaloids, however, it has an isoquinoline rather than a phenanthrene ting system. Noscapine was first isolated in 1817 but its antitussive activity was not demonstrated pharmacologically until 1952 (63). Clinical studies have confirmed its effectiveness. It is not a narcotic and has a wide margin of safety when given orally. Death could be produced in rats only with doses > 800 mg/kg (64). Noscapine is isolated from the water-insoluble residue remaining after processing opium for the manufacture of morphine. 

B. HCl, m.p. 242-3°). The methiodide, m.p. 104-7°, of this, on treatment with potassium hydroxide in methyl aleohol, yielded 5 6-pimethoxy-8-vinylphenanthrene, m.p. 86-7°, along with dimethyl-de-iV-methylnorroemerine, oil, [aju + 13-55° (EtOH) the methiodide, m.p. 278°, of this, on like treatment also yielded 5 6-dimethoxy-8-vinyl-phenanthrene, whose identity was established by its oxidation by permanganate to 5 6-dimethoxyphenanthrene-8-earboxylie aeid. Rcemerine is, therefore, 5 6-methylenedioxy-iV-methylaporphine, and this eon-stitution has been confirmed by Marion and Grassie s synthesis of the alkaloid. 

The plant is known elaborate a series of quite unusual phenanthrene alkaloid derivatives, of which aristoliukine-C, aristofolin A and E, aristolochic acid-la methyl ester, and aristolochic acid. Other chemical constituents found in this plant are flavonoid glycosides such as kaempferol-3-O-rutinoside and quercetin kaempferol-3-O-rutinoside (3,4). Exposure to Aristolochiaceae family is associated with the development of cancer in humans. A significant advance is the toxicological effects of aristolochic acid has been provided by the work of Pezzuto et al. They showed that aristolochic acid is a mutagen... 

Salutaridinol 7-0-acetyltransferase catalyzes the conversion of the phenanthrene alkaloid salutaridinol to salutaridinol-7-Oacetate, the immediate precursor of thebaine along the morphine biosynthetic pathway in P. somniferum (Fig. 10.7).26 Acetyl CoA-dependent acetyltransferases have an important role in plant alkaloid metabolism. They are involved in the synthesis of monoterpenoid indole alkaloids in medicinal plant species such as Rauwolfia serpentina. In this plant, the enzyme vinorine synthase transfers an acetyl group from acetyl CoA to 16-epi-vellosimine to form vinorine. This acetyl transfer is accompanied by a concomitant skeletal rearrangement from the sarpagan- to the ajmalan-type (reviewed in2). An acetyl CoA-dependent acetyltransferase also participates in vindoline biosynthesis in Catharanthus roseus, the source of the chemotherapeutic dimeric indole alkaloid vinblastine (reviewed in2). Acetyl CoA deacetylvindoline 4-O-acetyltransferase catalyzes the last step in vindoline biosynthesis. A cDNA encoding acetyl CoA deacetylvindoline 4-0-acetyltransferase was recently successfully isolated.27... 

Several tetra- and pentacyclic systems were prepared from Pro, which was first -substituted with naphthalene or phenanthrene rings whereupon the cyclization took place. Such reactions were used for synthetic ap-proaehes toward alkaloids vinceten from Cynachum vincetoxicum (the tetrahydrobenzo /]pyrrolo[l,2-Z ]isoquinoline system 146) (79LA1212 84AJC819) or tylophorine (65T2573). 

Morphine Morphine, 4,5-epoxy-17-methymorphin-7-ene-3,6-diol (3.1.19), is the oldest and most weU-known analgesic. It is made from opium— the dried, milky sap of unripe opium poppy bulbs, whose analgesic properties have been known for over 3000 years. This plant also contains a large number of other alkaloids that are subdivided into groups of phenanthrenes and benzyhsoquinoline. However, ways of making synthetic morphine have also been proposed. One of the proposed, exquisite, multi-phase methods of morphine synthesis is described below. 

The natural Aristolochia N-containing substances may be divided into three structural types nitrophenanthrenic acids, phenanthrene lactams, and isoquinoline alkaloids. 

Several inhibitors of AChE have been developed for use in treating Alzheimer s disease, which requires that the drugs readily enter the CNS. These inhibitors are structurally unrelated and vary in their mechanism of inhibition, although all are reversible inhibitors. Tacrine (Cognex) is a monoamine acridine. Donepezil (Aricept) is a piperidine derivative that is a relatively specific inhibitor of AChE in the brain, with little effect on pseudo-ChE in the periphery. Galanthamine (Reminyl) is a tertiary alkaloid and phenanthrene derivative extracted from daffodil bulbs that is a reversible competitive inhibitor of AChE it also acts on nicotinic receptors. 

Opium alkaloids are nonpeptide agonists for the opioid peptide hormone receptors. The dried latex of Papaver somniferum (opium), or the seed capsule of the plant itself, are the sources of almost 25 alkaloids. Some simple isoquinolines from opium, like papaverine (5.86), are antispasmodics. The principal alkaloid ( 10% of the total) is morphine (3.11), which is also an isoquinoline (rings C and E) but can addihonally be considered a phenanthrene derivahve (rings A, B, and C). 

Chemical class Piperidine Carbamate Phenanthrene alkaloid... 

The opium is obtained from the opium poppy Papaver somniferum. It contains two type of alkaloids e.g. phenanthrene derivatives (morphine, codeine thebaine) and benzyl isoquinoline derivatives (papaverine and noscapine). 

Opium alkaloids and derived phenanthrene alkaloids codeine, morphine, (Avinza, Kadian, MSContin, Roxanol), hydromorphone (Dilaudid), oxymorphone (Numorphan), oxycodone (dihydroxycodeinone, a component of Oxycotin, Oxydose, Oxyfast, Percodan, Percocet, Roxicodone, Tylox)... 

A very large number of substituted phenanthrenes have been made from stilbenes by this photocydization method, as have more complex polycyclic aromatic compounds by related reactions involving a single cydizatlon (e.g. 3.64 for chrysenes) or two, or more, successive cydizations le.g. 3.65). The reaction can be nicely adapted to provide a route from 1-benzylidenetetra-hydroisoquinolines to alkaloids of the aporphine family (e.g. 3.66). 

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