Scopolamine N-oxide

The derivatives of scopolamine (7) prepared by similar methods are available commercially. These include methscopolamine bromide (12), methscopolamine nitrate, and genoscopolamine (scopolamine N-oxide, 13). 

The N-oxides are converted to the corresponding tertiary bases in vivo. Atropine N-oxide and scopolamine N-oxide are slowly reduced to atropine and scopolamine in the animal body. Therefore, N-oxidation is a convenient technique for prolongingthe duration of the action of the alkaloidal bases. The N-oxides are said to be less toxic. 

Ci7H2ftBrN06, Scopolamine N-oxide hydrobromide monohydrate, 37B, 196 C17H32KN3O5S, 4,7,13,16,21-Pentaoxa-1,10-diazabicyclo-... 

Proton61 and carbon-1362 n.m.r. spectroscopy have recently been used extensively for the analysis of tropane alkaloids. The non-equivalence of H-6 and H-7 on the one hand and of H-2 and H-4 on the other in atropine and scopolamine is due to the non-symmetrical shielding by the tropic acid moiety. The configuration of A-substituents, e.g. N-oxides, has been determined by studying the deshielding of the 6- and 7/3-hydrogens. All of these results should be useful for the identification of new tropane alkaloids and other related systems in the future. 

There is less information about the metabolism of other tropane alkaloids but for those that are esters (e.g. hyoscyamine, scopolamine) hydrolysis of the ester bond takes place to some extent, yielding bases, which may be further transformed [45, 46], Rabbit serum has been found to have esterases that are relatively specific for esters of tropic acid, and this may account for the ability of rabbits to feed with impunity on leaves of Atropa belladona [47]. Mice transform released tropic acid to a glucuronide [48]. Oxidation also occurs, both in rats and humans, with the production of N-oxides and oxidative removal of the N-methyl group to make nor-derivatives [45,46]. 

V-Oxides of T5- and T6-type Alkaloids (T7-B). Two isomeric V-oxides of hyoscyamine (isomer 1 with equatorial N" -0 isomer 2 with axial N -0") were isolated from five famous species of the Solanoideae which have been widely used as medicinal plants Atropa belladonna, Hyoscyamus niger, Scopolia carniolica (Hyoscyameae clade), Mandragora officinarum (Mandragoreae clade), and Datura stramonium (Datureae clade) (Philippson and Handa 1975b). In addition, isomer 1 of the V-oxides of scopolamine (hyoscine) was identified in the same species with the exception of M. officinarum. It may be assumed that these compounds are also present in other species in minor concentrations they might have been overlooked in other studies on tropane alkaloids of the classical tertiary amine type due to the fact that the identification of V-oxides needs different methods. It may be added that also anisodamine V-oxide was identified in one species Physochlaina alaica). 

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