Alkaloids scopolamine

S. Wada, T. Yoshimitsu, N. Koga, H. Yamada, K. Oguri, H. Yoshimura, Metabohsm in vivo of the Tropane Alkaloid, Scopolamine, in Several Mammaban Species , Xenobiotica 1991, 21, 1289-1300. 

Furthermore, central-acting antimuscarinic drug are effective in the treatment of motion sickness. In this indication the alkaloid scopolamine has been shown to be effective. It can be applied orally, intra venously or via a transdermal therapeutic system. 

Atropa belladonna plants have been transformed with an H6H clone from H. niger. A. belladonna normally produces high levels of hyoscyamine, the precursor for the more pharmaceutically valuable alkaloid scopolamine (Fig. 3b). However, after transformation with the H6H gene, transgenic A. belladonna plants were shown to accumulate scopolamine almost exclusively (164). Additionally, the levels of tropane alkaloid production in a variety of hairy root cultures were altered by overexpression of methyltransferase putrescine-N-methyltransferase and H6H. Overexpression of both of these enzymes in a hairy root cell culture resulted in significant increases in scopolamine production (164, 165). Fluorinated phenyllactic acid substrates... 

There are considerable literatures on the production of tropane alkaloids in tissue and cell cultures derived firom various parts of intact plants [4]. In a number of cases, root differentiation is required for enhanced tropane alkaloid biosynthesis [3, 5]. The production of the economically valuable tropane alkaloids, scopolamine and hyoscyamine, by these cultures has not been commercially successful, however, root cultures are so far the best system to investigate the production and biosynthesis of tropane alkaloids. 

The genus Duboisia consists of three species, D. leichhardtii F. Muell, D. myoporoides R. Br. and D. hopwoodii F. Muell. The leaves of the former two species are a major source of the tropane alkaloids, scopolamine and hyoscyamine [1]. The alkaloid content in Duboisia can be affected by the environment, and a seasonal decline was noted in the scopolamine content between May and September in Australia [18]. Callus and root cultures of Duboisia have been studied with a view to developing a new method to obtain tropane alkaloids more efficiently and the results obtained supported the view that root organ culture is so far the best system for the production of tropane alkaloids [5]. Therefore suitable culture conditions for growth and alkaloid production must be established. 

Opticaiisomerism. Atropine (4-6) is the racemic form of hyoscyamine, which is the (S)-(-)-tropyl ester of 3a-tropanol (2). The carbon a to the carbonyl group is asymmetric. (5i)-(-)-Hyoscyamine is more active than R)-(+)-hyoscyamine as an anticholinergic (Table 3.11). The alkaloid scopolamine (7) is the (S)-(-)-tropyl ester of scopine (8) again the ( S)-(-) isomer is more active than (/ )-(+) isomer in its anticholinergic activities. 

S,B,RSP,yoh,Cinchona alkaloids,scopolamine, emetine,caffeine Detection with conductance detector... 

K Hagemann, et al. Monoclonal antibody based enzyme immunoassay for the quantitative determination of the tropane alkaloid, scopolamine. Planta Med 58 68, 1992. 

It may be mentioned in passing that comfrey was cited as a folkloric herb with curative powers but it is not mentioned that toxic PAs are a component (e.g., in Hoffman, 1999, pp. 76,90). As for alkaloids, among the anticancer agents mentioned are the Vinca alkaloids used successfully against childhood leukania, and the alkaloids scopolamine and hyoscyamine that occur in the mandrake root (and in other plants, such as henbane). 

Alkaloids (most alkaloids are pharmacologically active and many are of therapeutic value) Tropane alkaloids Scopolamine, apoatropine and atropine Adsorption Partisil Diethyl ether/ methanol (90 10) plus one per cent diethylamine... 

The isolation of the levorotatory hyoscine from the mother liquors from the preparation of i-hyoscyamine from Hyoecyamus muticu L. was reported in 1881. From early analyses (20) the new base was assigned the formula CitHjsOjN but this was subsequently revised to Ci7H2i04N (25, 52). In 1892 a second alkaloid, scopolamine (52), with the formula Ci7Hji04N, was isolated from Scopolia atropoides Bercht and Presl. However, the conversion of hyoscine and scopolamine to the same hydrobromide (25) established that they were one and the same base. 

PMT and H6H, which catalyze the first and last steps, respectively, in the biosynthesis of the tropane alkaloid scopolamine (Scheme 3), were localized to the pericycle in the roots of A. belladonna and Hyoscyamus muticus (Fig. 2A) 132,145). PMT also catalyzes the first step in nicotine biosynthesis (Scheme 3) and has been localized to the endodermis, outer cortex, and xylem in N. sylvestris (244,245). In contrast, TR-I, an intermediate enzyme in the tropane alkaloid pathway, resides in the endodermis and nearby cortical cells (Fig. 2A) (135) thus, intermediates of tropane alkaloid metabolism must also be transportai between cell types. The biosynthesis and storage of acridone alkaloids were also associated with endodermis in Ruta graveolens (246). 

Increasing the concentration of the alkaloid scopolamine in medicinal plants has been the target of much research. First results were obtained in the late 1980s when somatic hybridization was used to increase the content in Datura species, and the transformation of Atropa belladonna with the enzyme hyoscyamine-6-beta-hydroxylase lead to a shift from hyoscyamine to a nearly exclusive production of scopolamine (Figure 2.7) [60]. 

The leaves of the Australian native tree Duboisia myoporoides are the commercial source of the pharmacologically useful alkaloid scopolamine. It is known that this plant contains a 3% of hyoscyamine in October (spring) and this alkaloid is almost complete transformed into scopolamine by April (autumn) [1]. For this reason, it is important to identify the optimum harvest time in order to maximize the yield of the desired compound. 

The operating potential was chosen near the upper plateau of the voltammogram, since this offered the best compromise between a high response and a low background current (+1.2 V vs. SCE, saturated calomel electrode, similar to +1.2 V vs. Ag/AgCl). The structurally related alkaloids scopolamine arid apoatropine were also oxidized at this potential. The lower limit of the linear dynamic range was 2.9 ng for atropine. EC offered at least a tenfold lower detection limit and wider linear response than UV at 220 nm. 

The current status of knowledge of the biosynthesis of the tropane alkaloids is almost paradoxical our understanding of the mechanisms by which plants assemble the tropane nucleus (1) still leaves much to be desired whilst some of the late events in the formation of one particular tropane alkaloid, scopolamine (2), are understood in great detail. Applications of this knowledge in the sense of metabolic engineering of medicinal plants have even been described [5]. 

The most noted representative of this group is the alkaloid scopolamine (27), whose name comes from the species of the genus Scopolia from where it was originally isolated [30]. 

Tropine [6.66) is a precursor for the more extensively oxygenated alkaloids, scopolamine [6.73) and meteloidine [6.75), presumably by... 

Hyoscyamine 6j8-hydroxylase (H6pH) is a 2-ODD enzyme that catalyzes a critical step in the biosynthesis of the tropane alkaloid scopolamine (Fig. 3) in members of the Solanaceae [82],... 

Galenical preparations such as tinctures, dried extracts, and mixtures of Atropa belladonna, Hyoscyamm niger, and Datura stramonium, still find clinical use, but most physicians prefer the pure alkaloids. Scopolamine (5), which is (-)-hyoscine, is more active than (-l-)-hyoscine, while the anticholinergic affects of atropine are almost entirely due to (—)-hyoscyamine (6) which forms 50 per cent of the natural racemate. 

In general,the alkaloids isolated from the leaves had a higher specific activity than those obtained from the roots. Removal of the flowers increased the level of activity in the root alkaloids. Scopolamine had a lower activity than hyoscyamine, consistent with it being formed from the latter alkaloid). 

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