Isoquinolines phenanthrene alkaloid

In relation to their chemical structure and action, they can be classified into two categories. The first are phenanthrene alkaloids and are under international control morphine (MO), codeine (COD), and thebaine (TB), which act on the central nervous system and are used as analgesics, narcotics, and potentially addicting compounds (pain relievers). Heroin is synthesized from MO. The second group is isoquinoline alkaloids Papaverine (PV) and narcotine (also known as noscapine). Narcotine acts only to relax involuntary smooth muscles, for which it is considered an antitussive, and lacks addictive, analgesic, respiratory, narcotic, depressant, and sedative properties. Next to MO, which constitute about 10% by weight of raw opium, is the second most abundant alkaloid present in opium. The three last alkaloids (PV, narcotine, and narceine) are not under international control specially, narcotine and narceine which have scarcely any medical or other uses. Consequently, the five economically significant alkaloids of opium are MO, COD, TB, PV, and narcotine. 

In some alkaloid reference volumes, alkaloids such as berberine and related molecules have been classified as benzo[r]phenanthrene alkaloids. We have chosen to classify these alkaloids, for the purposes of this review, as isoquinoline-derived alkaloids, which are discussed in Section 7.9. Isoquinoline is the largest constituent of these alkaloids that falls into a trivial classification, which was the basis of our decision. 

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. 

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). 

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

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). 

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). 

The opium alkaloids, which are obtained from Papaver somniferum, contain two groups of compounds compounds with phenanthrene derivatives, consisting of morphine, codeine, and thebaine and compounds with isoquinoline derivatives, consisting of papaverine and noscapine. 

A useful and timely supplementary listing of new aporphines, oxoaporphines, phenanthrenes, and 4,5-dioxoaporphines has appeared.1 The alkaloids of Glaucium species, which include several aporphines and oxoaporphines, have been tabulated2 and a general discussion of the chemistry and biogenesis of isoquinoline alkaloids, including the aporphines, has been presented.3... 

NOSCAPINE (NARCOTINE) As an optically active, laevorotatory substance noscapine is found in opium (2-12%). This alkaloid is, next to morphine, the most plentiful of the opium alkaloids. Structurally it differs from the phenanthrene derivatives morphine and codeine by its phthalide isoquinoline— skeleton. 

The mass spectral behaviour of proaporphine alkaloids has been analysed. Microcrystalloscopic determination of phenanthrene-isoquinolines using antimony acid complexes has been carried out. ... 

Morphine, C17H19NO3, is the principal alkaloid of opium, which contains a large number of substances, such as fats, resins, acids, and gums in addition to twenty alkaloids which have been identified. Opium is the dried juice of the seed capsules of the white poppy. Laudanum is an alcoholic extract of opium. Morphine, which melts at 230°, is used as a narcotic. When distilled with zinc-dust it yields phenanthrene, isoquinoline, pyridine, and pyrrole. 

The regioselective ET-sensitized addition of primary amines has been cleverly employed by Yasuda and co-woikers in the synthesis of isoquinolines and related alkaloids. For example, the DCNB-sensitized photoamination of stilbene with 2-hy-doxypropylamine in an acetonitrile-water solution yields the adduct 98, which is converted to the benzylisoquinoline 99 upon treatment with CFjSOjH, The P-hydroxyl group of ethano-lamine can be replaced with acetal or vinyl groups which also can serve as precursors of the carbocation required for the acid-catalyzed ring-forming reaction. Analogous reaction sequences have been used to convert phenanthrene to aporphines. ... 

Synthetic alkaloid regarded as the parent of the phenanthrene-isoquinoline series. Froehde s rea nt —> green. Mandelin s reagent —>... 

Most of the alkaloids containing an isoquinoline structure that are considered are presented in the following order simple iso quinolines, isoquinolones, and phenethylammonium compounds benzyltetrahydroi-soquinolines bisbenzylisoquinolines and bisbenzyltetrahydroisoquino-lines protoberberines and tetrahydroprotoberberines proaporphines aporphinoids dehydroaporphines 7-substituted aporphines oxoapor-phines phenanthrenes miscellaneous isoquinohne-type alkaloids and nonisoquinoline alkaloids. 

The discovery of morphine marked the begiiming of organic alkaloid chemistry, and the further analysis of papaver alkaloids proceeded quickly. There are over 50 papaver alkaloids in all, nitrogenous organic bases, but they can be divided into two major classes of papaver alkaloids - the isoquinolines and phenanthrenes. The phenanthrenes are the most medically significant, with morphine, codeine, and thebaine acting as important opioid agonists. 

From the benzylisoquinolines are derived all the types of isoquinoline alkaloids found in the Annonaceae (Fig. 3) berberines, aporphines, oxoaporphines, phenanthrenes, cularines, morphinanedienones, isoquinolones, dimethylaminoethyl-benziles and bisbenzylisoquinolines. 

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