Alkaloids hyoscyamine

Duhoisia myoporoides. Yields of 3 per cent., mostly hyoscine, have been mentioned, but great variation in nature of alkaloidal content is on record, e.g., hyoscyamine, -hyoscyamine, hyoscine. Hyoscyamine and norhyoscyamine, but no hyoscine. Hyoscine or hyoscyamine or both. dZ-Hyoscine, tigloidine, valeroidine, poroidine and woporoidine present hyoscyamine and norhyoscyamine absent. The limits of these variations, at least as regards the two principal alkaloids, hyoscyamine and hyoscine, have probably been settled by Hills, Trautner and Rodwell, who confirmed the statement of Barnard and Finnemore that in the northern portion of the distribution area of this plant, it yields mainly hyoscine and in the southern section mainly hyoscyamine. In 54 samples of leaves from individual trees they found 0-9 to 4-0 total alkaloids in those from the northern section, with hyoscine as the chief component, and 1-0 to 2-7 from those of the southern section, with hyoscyamine replacing hyoscine. 

The cholinergic hallucinogens all have common chemical constituents that are responsible for their pharmacological effects (Robbers et al. 1996). These are the tropane alkaloids hyoscyamine, scopolamine (or hyoscine), and atropine (figure 9.16). It is scopolamine, and not atropine or hyoscyamine, which primarily produces the central and hallucinogenic effects because it is the only one that passes the blood-brain barrier sufficiently. However, all three have peripheral effects. Datura stramonium contains 0.1-0.65% tropane alkaloids, which is principally... 

Thus, the anticholinergic activity of the alkaloid hyoscyamine is almost entirely confined to the (—)-isomer, and the (+)-isomer is almost devoid of activity. The racemic ( )-form, atropine, has approximately half the activity of the laevorotatory enantiomer. An anticholinergic drug blocks the action of the neurotransmitter acetylcholine, and thus occupies the same binding site as acetylcholine. The major interaction with the receptor involves that part of the molecule that mimics acetylcholine, namely the appropriately positioned ester and amine groups. The chiral centre is adjacent to the ester, and also influences binding to the receptor. 

The tropane alkaloids (—)-hyoscyamine and (—)-hyoscine are found in the toxic plants deadly nightshade (Atropa belladonna) and thornapple (Datura stramonium) and are widely used in medicine. Hyoscyamine, usually in the form of its racemate atropine, is used to dilate the pupil of the eye, and hyoscine is employed to control motion sickness. Both alkaloids are esters of (—)-tropic acid. 

Nicotine affects the nervous system, interacting with the nicotinic acetylcholine receptors, and the tight binding is partially accounted for by the structural similarity between acetylcholine and nicotine. Curare-like antagonists also block nicotinic acetylcholine receptors (see Box 6.7). There are other acetylcholine receptors, termed muscarinic, that are triggered by the alkaloid muscarine. The tropane alkaloid hyoscyamine (see Box 10.9) binds to muscarinic acetylcholine receptors. 

Tropane alkaloids Hyoscyamine 6/3-hydroxylase Hyoscyamus niger Atropa belladonna... 

Hyoscyamus bohemicus F. W. Schmidt H. niger L. Liang Shi (Henbane) (root, leaf) Alkaloid, hyoscyamine, hyoscine, scopolomine, hyoscypierin, choline, mucilage, albumin.60,144,450 This herb is toxic. Antispasmodic activity. 

N.A. Tropane alkaloids (hyoscyamine, hyoscine), flavonoids, withanolides, coumarins, tannins.100 Treat asthma, coughs, fevers, skin conditions. 

The tropane alkaloids (—)-hyoscyamine and (—)-hyoscine are among the most important of the natural alkaloids used in medicine. They are found in a variety of solanaceous plants, including Atropa belladonna (deadly nightshade), Datura stramonium (thornapple) and other Datura species, Hyoscyamus niger (henbane), and Duboisia species. These alkaloids... 

FIGURE 14.3 The henbane (Hyoscyamus niger Linne), a member of the nightshade family, whose leaves, with or without the tops, constitute the official drug Hyoscyamus and are a source of the valuable medicinal alkaloids hyoscyamine and scopolamine. 

Both untransformed (Hashimofo and Yamada, 1994) and transformed root cultures of Datura, Hyoscyamus, Atropa and Duboisia species (Robins and Walton, 1993) accumulate high levels of fhe fropane alkaloids, hyoscyamine and scopolamine (Fig. 2.3). These medically imporfanf fropane alkaloids present not only an interesting biochemical problem but also a realistic... 

The tropane alkaloids hyoscyamine and scopolamine (Fig. 3a) fnnction as acetylcholine receptor antagonists and are nsed chnically as parasympatholytics. The illegal drug cocaine also... 

Patterson S, O Hagan D. Biosynthetic studies on the tropane alkaloid hyoscyamine in Datura stramonium hyoscyamine is stable to in vivooxidtion and is not derived from Uttorine via a vicinal interchange process. Phytochemistry 2002 61 323-329. 

DI-HETERO-CYCLIC ALKALOIDS Hyoscyamine, Atropine, Tropine... 

Both alkaloids have (+) and (-) forms but only the (-) hyoscyamine and (-) scopolamine are active. The biosynthetic pathway of tropane alkaloids, Fig. (1) is not totally understood, especially at the enzymatic level. Edward Leete has pioneered the biosynthetic studies of tropane alkaloid since 1950"s using whole plants and isotope labels [85-86]. The tropane alkaloid hyoscyamine is bioconverted by the enzyme H6H (hyoscyamine 6p-hydroxylase, EC 1.14.11.11) to scopolamine via 6p-hydroxyhyoscyamine. Hyoscyamine is the ester of tropine and (S)-tropic acid. The (S)-tropic acid moiety derives from the amino acid L-phenylalanine, while the bicyclic tropane ring derives from L-omithine primarily or L-arginine via tropinone. Tropinone is stereospecifically reduced to form either, tropine which is incorporated into hyoscyamine, or on the other hand into pseudotropine which proceeds to calystegines, a group of nortropane derivates that were first found in the Convolvulaceae family [87]. 

Atropine is an ester, and on hydrolysis yields a basic substance, tropine, and optically inactive tropic acid (1). It has been shown that the alkaloid hyoscyamine, which is also obtained from belladonna and is laevo-rotatory, is the ester of tropine with laevo-tropic acid (2), and therefore atropine appears to be racemic hyoscyamine. This view of the nature of atropine has been confirmed by Ladenburg (3), and dextro-hyoscyamine has also been prepared by the union of tropine with dextro tropic acid (4). 

Chapter 6 Datura Alkaloids Hyoscyamine and Atropine C17H2303N M.W. 289... 

The clinically used Solanaceae-alkaloids hyoscyamine, atropine and scopolamine are esters of tropic acid. Since tropic acid has an asymmetric C-atom, these alkaloids occur in L-, D- and DL-forms, the L-form of which is the also most pharmacologically active. 

Alma R. Hutchens Indian Herbalogy of North America cites herbs that, according to medical folklore, are said to act against hydrophobia or rabies, some of which are in common with Heinerman s listing. In addition to rue, there is mention of balsam fir, beech tree, echinacea, henbane, Jimsonweed, rue, skullcap, St. John s wort, and tansy. Jimsonweed and henbane contain the alkaloid hyoscyamine, as do some other members of the family Solanaceae, or nightshade family. The family Solanaceae, incidentally, is well represented in HartweU (1982b). 

Coumarins scopoletin, and 7-0-glucoside Alkaloids hyoscyamine, scopolamine (see Fig. 27,28, Chap. 1 Alkaloid Drugs)... 

Atropine is the racemic form of the alkaloid /-hyoscyamine. The latter is a common tropane alkaloid found in solanaceous plants, such as belladonna (Atropa belladonna), henbane (Hyoscyamus niger), and the deadly nightshade (Datura stramonium). During extraction, Z-hyoscyamine is readily racemized to atropine, which does not occur naturally in more than traces. 

Tropane alkaloids Hyoscyamine 6 -hydroxylase Hyoscyamus niger... 

Scheme 3. Biosynthesis of the tropane alkaloids hyoscyamine and scopolamine, the ca-lystegines, and nicotine. Molecular clones have been isolated for the enzymes shown. Abbreviations CYP82E4, nicotine A-demethylase H6H, hyoscyamine 6jS-hydroxylase ODC, ornithine decarboxylase PMT, putrescine A-methyltransferase TR-I, tropinone reductase-I TR-II, tropinone reductase-II.

Beginning in the nineteenth century, chemists and physicians began extracting and isolating the active principles of these plants. In 1881 the alkaloid hyoscyamine (atropine, belladonna) was isolated from the plants mentioned above. It is now used in medicine. 

In contrast to GC-MS, a wide range of tropane alkaloids, including A -oxides and calystegines, can be analyzed by HPLC without prior derivatization. Enantiomeric separation of atropine 5 and scopolamine 6 racemic mixtures has been also achieved [22]. A number of HPLC methods have been published for routine quantification of the major tropane alkaloids hyoscyamine 1 and scopolamine 6 in plant samples. The use of UV detectors however is limited to compounds with UV adsorbing (aromatic or other) functionality. This disadvantage, however, is easily overcome by using HPLC coupled with MS detectors [22]. A typical HPLC separation of hyoscyamine 1 and scopolamine 6 is presented on Fig. 7.2. 

It should be noted that the two ploidy levels of the transformed root cultures of D. stramonium L. show significant differences as regards the spectrum of the biosynthesized alkaloids. Unlike the diploid, tetraploid-transformed roots biosynthesized ten alkaloids. One of them (entry 15, Table 7.3) was not detected in the diploid root culture of D. stramonium L. The pharmacologically active alkaloid hyoscyamine 1 is the principal alkaloid biosynthesized by both root cultures at 78.8% and 56.6% of the total ion ciuxent in the diploid and tetraploid-transformed roots of D. stramonium L., respectively (entry 9, Table 7.3). In contrast to diploid roots, which accumulate 7.12% apoatropine, the tetraploid-transformed root culture biosynthesize 3-acetoxytropane (28.4%) as a second... 

Cover illustration. Flowers of Ipomoea purpurea (L.) Roth [cultivar Convolvulaceae] (left) and Solandra maxima (Sesse Mocino) PS. Green [Solanaceae] (right). Plotted on the photographs are corresponding constituents the major anthocyanin pigment and the major alkaloid hyoscyamine, respectively. 

Figure 4.1a. Grafting experiments with Solanaceae. Grafting on Datura stramonium roots a—Datura stramonium control on D. stramonium b—Datura tatula on D. stramonium c— Cyphomandra betacea on D. stramonium d—Nicotiana tabacum on D. stramonium. In all cases the aerial part (scion) accumulated tropane alkaloids like Datura stramonium, except in b, where the alkaloid hyoscyamine was converted into hyoscine.

Phenylalanine as a Precursor.— Tropic acid is found in Nature as the add moiety of the ester alkaloids hyoscyamine and hyosdne. A large amount of information, some conflicting, has been published in the past decade on the origin of this relatively simple molecule. We will review these data critically in the hope that it will aid work on the currently unsolved problem of its biosynthesis. It was discovered in 1960 that the administration of [3- C]phenylalanine to intact Datura stramonium plants yielded tropic acid having essentially all its activity at C-2. Later workers confirmed this result in D. stramonium (intact plants) and D. metel (sterile root cultures). It was then established that the other carbons of the phenylalanine side-chain were used for the production of the side-chain of tropic acid. The pattern of labelling found in the tropic... 

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