Scopine Scopolamine

M. and M. Polonovski found that when scopolamine is treated with hydrogen peroxide, there is formed in addition to scopolamine iV-oxide [a]i, — 14° (H2O), [B. HBr, m.p. 153°] the quaternary base scopinium, isolated in the form of its bromide, m.p. 209-10°. The latter is reduced by sodium amalgam to a tertiary base, stereoisomeric with scopine and related to the latter as -tropine is to tropine and, therefore, named -SCOPINE. It yields crystalline salts B. HCl, m.p. 257-8°, aurichloride. 

Sauroxine saururine, 753, 7S4 Saussufea Cappa saussurine, 782 Sceleranecic acid, 605 Sceleratlne, 602, 605 Schcenocaulon officinale, 700 Scopine, 64, 66, 88, 107 -scopine, 89 ncr-0-scopine, 89 Scopolamine, see Hyoscine ... 

Atropine and scopolamine are esters of tropoyl acid—tropine and scopine, respectively. Scopine differs from tropine only in that it has an expoxide bridge between carbon atoms Cg and C7 of tropine. 

As noted from its formula (see Figure 14.2), scopolamine differs from atropine chemically in having an oxygen atom attached to the end carbon atoms of the scopine part of the molecule. Scopolamine is levorotatory but is readily racemized to the t/,/-form designated as atroscine. 

Hyoscine (= 6,7-Epoxytropine tropate Scopine tropate Scopolamine) (tropane)... 

SYNS ATROCHIN ATROQUIN 6-P,7-P-EPOXY-3-a-TROPANYL S-(-)-TROPATE EPOXYTROPINE TROPATE HYOSCIN E (-)-HYOSCINE HYOSOL ISOPTO HYOSCINE 9-METHYL-3-OXA-9-AZATRI-CYCLO(3,3.1.o2. )NONAN-7-OL TROPATE (ester) OSCINE SCOPIXE TROPATE (-)-SCOPOLAMINE TROPIC ACID, ESTER with SCOPINE TROPIC ACID, 9-METHYL-3-OXA-9-AZATR1CYCLO(3.3.1.o2" )NON-7-YL ESTER... 

The amino alcohol derived from scopolamine (7), that is, scopine (8), has the axial orientation of the 3-OH group but in addition has a -oriented epoxy group bridged across the 6, 7 positions. 

The synthesis of scopolamine differs from that of atropine in the synthesis of the amino alcohol, scopine portion of the molecule. Fodor and CO workers (60, 73, 74) have synthesized scopine starting from 6-j3-hydroxy-3-tropanone. Esterification of scopine with 0-acetyltropyl chloride and mild hydrolysis of the acetylsco-polamine give scopolamine. 

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. 

These alkaloids are from a structural point of view, esters between the alcohols such as tropine in e.g. hyoscyamine and scopine in e.g. scopolamine and different ahphatic and aromatic acids, mainly tropic acid. The tropane alkaloids within the family Solanaceae belong mainly to the tropine series, whereas the Coca-alkaloids from the family Erythroxylaceae mainly belong to the pseudo-tropine series. 

The formation of the A-oxide was avoided when trifluoroperacetic acid was reacted with the trifluoroacetate of acetyltropenol (67a, b). Recently it has been shown that hydrogen peroxide in formic acid gave a still better yield of epoxides without detectable A-oxides (67b). Acetylscopine (LXV) has been isolated as the picrate, (m.p. 212°) (67a), identical with the sample obtained from scopine (XLa) (75) hydrochloride by acetyl chloride (67a). The conversion of acetylscopine into ( ) scopolamine (LXV->XLb) has been realized (67b). Hydrolysis with A NaOH in acetone led to scopine (XLa), the hydrochloride of which was acylated, in turn, with acetyltropoyl chloride in nitrobenzene to acetylscopolamine besides a number of by-products. Separation was achieved using cellulose powder chromatography in butanol-A HCl. Acid hydrolysis of this ester with 2A HCl led to ( ) scopolamine hydrochloride (XLb) (67b) identical with the natural... 

An alternative route to scopolamine and hyoscine has been reported. When tropenol is acylated with either racemic or active acetyltropoyl chloride and the respective acetyldehydroatropine or acetyldehydro-hyoscyamine is oxidized with performic acid, there is generated acetyl-scopolamine or acetylhyoscine, respectively (67b). The oxidation of scopine (LXXXIV) to scopinone (LXXXV) has been realized (133). 

LXIV). Scopine is readily converted by either acid or base to scopoline (174). Hence Z-scopolamine must be 1-tropylscopeine (LXVI). 

Synonyms /-scopolamine 6,7-epoxytropine tropate scopine tropate hyoscine 6-j6-... 

Duboisia leichhardtii Roots Pseudotropine Scopine Scopoline Atropine Acetylpseudotropine Acetylscopine Acetylscopoline Scopolamine 324... 

PoETHKE et al. [125, 173] have worked with belladonna herbs and tinctures. They used silica gel G and chloroform-acetone-diethylamine (50 + 40 + 10) as solvent. Oswald and Flhck [151—153] have chromatographed hyoscyamine and other alkaloids from this material, notably belladonnine, apoatropine, aposcopolamine, scopine and scopoline. Six solvents were used, of which the best was found to be butanone-methanol-7.5% ammonium hydroxide (60 + 30 + 10) the Dragendorff reagent was employed for detection. The method was worked out also for quantitative determination (planimetric evaluation) (limit of error 5.8%). A linear relation was found between spot area and amount of alkaloid, provided that the amount of substance did not fluctuate by more than 20%. In this way it was possible to determine the mixture of hyoscyamine and atropine in the presence of scopolamine (hyoscine) in some of the plant organs of Atropa belladonna. Datura stramonium, Hyoscyamus niger and H. muticus [153]. 

Rare Derivatives of Scopolamine (Hyoscine) Not Included in Table 3.1. Another 3-acyloxyscopine derivative, 3-phenylacetoxy-6p,7P-epoxytropane was identified in the seeds of Datura ferox (Vitale et al. 1995). It may be assumed that this metabolite is 3a-substituted since only 3a-acyloxy congeners were found in this species and natural 3P-substituted scopines are unknown in general however, the stereochemistry at C-3 has not yet been determined. 

S)-Hyoscyamine and (6)-scopolamine are esters of the amino alcohols tropine and scopine with ( S)-tropic acid, which is derived from phenylalanine (Fig. 3). The two alkaloids occur exclusively in the Solanaceae family. They act as antagonists of muscarinic acetylcholine receptors (parasympatholytics) and lead to an increase in pulse rate, relaxation of smooth muscles, e.g., in the gastrointestine and the bronchial tract, reduction of salivary, bronchial, gastric, and sweat gland secretion. While hyoscyamine is a central stimulant, scopolamine depresses the central nervous system. 

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