Alkaloid properties

The fact that these alkaloids have both phenolic and alkaloidal properties causes some problems in extraction from aqueous media by conventional means, particularly for the secondary amines. Thus schumagnine (33) and A-meth-ylschumagnine (34) were present in the aqueous fraction of the alcoholic extract of S. magnificum but on acidification were taken into chloroform (13). 

The alkaloids are also relevant to drug design. Alkaloids are complex heterocyclic compounds that contain nitrogen and thus have base-like (hence the term alkaloid ) properties they are extremely structurally diverse. Nicotine is one of the simplest alkaloids. Oxidation of nicotine produces nicotinic acid, a vitamin that is incorporated into the important coenzyme nicotinamide adenine dinucleotide, commonly referred to as NAD" (oxidized form). The neurotransmitter serotonin is an alkaloid containing the aromatic indole ring system. 

Although their presentiy accepted stmctures were unknown, they were characterized with the tools available at the time. Because morphine (2, R = H), C22H22NO 3, was shown to have properties similar to the basic soluble salts obtained from the ashes of plants (alkah) it was categorized as a vegetable alkaU or alkaloid, and it is generally accepted that it was for this case the word was coined. 

Both of the alkaloids anhalamine (62) from l ophophora williamsii and lophocerine (63) from l ophocereus schotti were isolated (after the properties of purified mescaline had been noted) in the search for materials of similar behavior. Interestingly, lophocerine, isolated as its methyl ether, after dia2omethane treatment of the alkaU-soluble fraction of total plant extract, is racemic. It is not known if the alkaloid in the plant is also racemic or if the isolation procedure causes racemization. 

Patients receiving monoamine oxidase inhibitors (MAOI) as antidepressant therapy have been especially subject to the hypertensive effects of vasoactive amines (52). These dietary amines have also been impHcated as causative agents ia migraine. Other aaturaHy occurring alkaloids (qv) have been recognized for centuries as possessing neurological stimulant and depressant properties. 

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). 

Chemical Properties. Reactions of quaternaries can be categorized iato three types (169) Hoffman eliminations, displacements, and rearrangements. Thermal decomposition of a quaternary ammonium hydroxide to an alkene, tertiary amine, and water is known as the Hoffman elimination (eq. la) (170). This reaction has not been used extensively to prepare olefins. Some cycHc olefins, however, are best prepared this way (171). Exhaustive methylation, followed by elimination, is known as the Hoffman degradation and is important ia the stmctural determination of unknown amines, especially for alkaloids (qv) (172). 

The early stmctural evideace, physical properties, and aromaticity of isoquiaoline have been discussed at the beginning of this article. Two additional trivial names are encountered occasionally 2-benzaziae and leucoline. The widespread occurrence of this stmcture ia such important alkaloids as those found ia cactus, opium, and curare has created a long-standing iaterest ia its syathesis and properties (4). 

The antimalarial properties attributed to preparations from Dichroa febrifuga by the Chinese were confirmed about 1944 and two alkaloids, febrifugine (999) and isofebrifugine (1000), were isolated eventually. After difficult structural elucidations, syntheses of ( )-febrifugine followed it proved to be half as active as the natural material, itself far better than quinine, but the therapeutic index was disappointingly low (67HC(24-l)490). 

Amethopterin — see Folic acid, 4-amino-4-deoxy-10-methyl-Amicetin isolation, 3, 147 Amicibone properties, 7, 545 Amide alkaloids synthesis, 1, 470 Amides... 

Many classes of natural product possess heterocyclic components (e.g. alkaloids, carbohydrates). However, their structures are often complex, and although structure-based names derived by using the principles outlined in the foregoing sections can be devised, such names tend to be impossibly cumbersome. Furthermore, the properties of complex natural product structures are often closely bound up with their stereochemistry, and for a molecule containing a number of asymmetric elements the specification of a particular stereoisomer by using the fundamental descriptors (R/S, EjZ) is a job few chemists relish. 

The common hemlock, Conium maculatum, contain five alkaloids. Power and Tutin found a similar mixture in fool s parsley, and a volatile alkaloid resembling coniine i.s stated to occur in certain aroids. According to Svagr, water hemlock Cicuta virosa) owes its poisonous properties to toxin and not to cicutine, a name sometimes used as a synonym for coniine. The toxic properties of hemlock juice have been known ftom very early times thus it was the chief ingredient in the poison administered to criminals by the Greeks. The leaves and the unripe fruits are the parts used in medicine. The following are the names and formulae of the alkaloids —... 

HjO), a picrate, m.p. 253° (dec.) and furnishes a dibenzoate, whose sulphate has [a] ° + 52-1° (EtOH) and hydrochloride, B. HCl. 2H2O, m.p. 115° or 205° (dry), + 41-8° (dilute alcohol) and nitrate, B. HNO3, m.p. 197°. On reduction with hydriodic acid and red phosphorus the dihydroxytropane is converted into tropane and on treatment with phosphorus oxychloride it yields a base, CgHjgON, b.p. 188°/752 mm., picrate, m.p. 177° (dec.). This dihydroxytropane is probably represented by formula (XIII).The dibenzoyl-derivative has local ansesthetic properties. The wovaleryl ester is the alkaloid valeroidine found in Duboisia myoporoides (p. 90). 

The Freneh authors realised that in eertain respeets this symmetrical formula, with the two equivalent nitrogen atoms, was difficult to reconcile with certain of the properties and reactions of the alkaloid. ... 

This, on reduction with zinc dust and acetic acid, yielded the corresponding oxime, which was further reduced by sodium amalgam to -3 4 5-trimethoxyphenylethylamine, CgHjj(OMe)3. CH. CH. NHg, and this proved to be identical with mezcaline (I). Like the latter, it behaves on analysis as if it contained the grouping —NHMe but this had already been disproved by Heffter. Interest in the remarkable physiological properties attributed to mezcaline has led to many syntheses of this alkaloid and of its isomerides and analogues. ... 

The first scheme for the separation of the six chief alkaloids of opium, VIZ., morphine, codeine, thebaine, papaverine, narcotine and narceine, is probably that of Plugge. Much later Kljatschkina investigated for each of these six bases the properties by means of which isolation and estimation could probably be effected and, on the basis of the results, devised a plan for such analyses. More recently Anneler has published a detailed account of a scheme with the same objective. l Attention had already been given to complex, systematic analyses of this kind, in connection with examination of the mixtures of opium alkaloids, which have long been in use in medicine in these at first only morphine and other alkaloids were determined, but in the more recent schemes provision is made for the estimation of each alkaloid. ... 

Mention may also be made here of some recent investigations in which comparison of physical properties of the chief opium alkaloids has been... 

Phaeanthine, C3JH42O0N2. (Item 8 list, p. 350.) This alkaloid was isolated by Santos.It has m.p. 210°, [a]u°° — 278° (CHCI3), yields a hydriodide, m.p. 268°, picrate, m.p. 263°, aurichloride, m.p. 170-1°, and a platinichloride, m.p. 280° (dec.), and contains four methoxyl and two methylimino groups. By the Hofmann degradation process it yields an optically inactive methine base A, m.p. 173°, which is oxidised by potassium permanganate in acetone to 2-methoxy-5 4 -dicarboxydiphenyl ether (p. 348). A comparison of the properties of phseanthine and tetrandrine by Kondo and Keimatsu indicates that these two alkaloids are optical antipodes, so that phseanthine will be represented by either (XXXIX) or (XL) as given on p. 348, 1 and of these two formula (R = Me) one must represent oxyacanthine methyl ether and the other berbamine methyl ether (centres of asymmetry d- and 1-) tetrandrine (centres of asymmetry both d-) and phseanthine (centres of asymmetry both 1-). 

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