Pseudo tropine

The different configurations of the salts obtained by var3dng the sequence of alkylation are well illustrated by the reaction of pseudo-tropine (14) with ethyl iodoacetate to give 15, while the opposite order... 

Beweis der Konfiguration des Pseudo-tropins, bezw. des Tropins, by E. Hardegger and H. Ott, Helv. Chim. Acta, 36 (1953) 1186-1189. 

Tropine is optically inactive, and so also is pseudo-tropine the isomerism is dependent on molecular asymmetry (cis-trans isomerism).—(Barrowcliff and Tutin, J.C.S., 95,1909,1966.)... 

It will thus be seen that the tropeines derived from tropine itself have a strong mydriatic action, but only a weak anesthetic action, while their stereo-isomerides, derived-from pseudo-tropine, have no mydriatic action, but are powerful local anesthetics. 

Pseudo-tropine is obtained from tropine by heating it with sodium amylate (10) and it is also obtained from tropinone—... 

Tropacocaine from Pseudo-tropine and Benzoic Anhydride... 

Approximately one mole of pseudotropine is heated with appox. one mol. of water and then refluxed with a slight excess of benzoic anhydride. The mixture is gently refluxed for approx 4 hours. The product is mixed with ether and hydrochloric acid. The aqueous layer is separated and diluted with more water. The aqueous mixture is extracted with half its volume with ether or appropriated solvent. The majority of unchanged pseudo-tropine remains in the aqueous layer. The ether solution is cooled, and the tropacocaine salt precipitated by the addition of an acid. Evaporation of ether will produce more tropacocaine. Refs. Blount 1933... 

Tropine and pseudo-tropine both possess the same structural formula, for, on oxidation, they each 3deld tropinone, whilst the latter, when reduced, gives a mixture of the two hydroxy-bases (Willstatter and Iglauer, Ben, 1900, 33,1170). Willstatter concluded, therefore, that a cis-/rans-isomerism, dependent on the relative positions in space of the hydroxyl and methyl groups, existed between tropine and pseudo-tropine. Objection to this explanation might be made on the ground that no quite parallel case of isomerism seems to have been observed, and it therefore appeared to the present authors that it should not be accepted unreservedly so long as another explanation is possible. 

The tropine molecule contains two similar asymmetric carbon atoms, and the base should therefore be capable of existing in a racemic and an internally compensated form. The possibility of these two optically inactive modifications being represented by tropine and pseudo-tropine had been considered by Willstatter, but he rejected this explanation, as both bases, on oxidation, yielded the same ketone. It seemed to the present authors, however, that the possibility of the difference... 

In view of the above considerations, therefore, it would appear that the formation of pseudo-tropine by the action of sodium amyloxide on tropine might be a process of racemisation, and this seemed to be in harmony with the experimental facts, since the change in question is never complete. Thus, in our experiments on the preparation of pseudo-tropine, about 35 per cent, of the basic product resulting from the treatment with sodium amyloxide was found to consist of an uncrystallisable mixture of tropine and pseudo-tropine, and Willstatter mentions that the yield of pure pseudo-base obtained by him did not exceed 50 to 55 per cent, of that theoretically possible. It appeared, therefore, that, the action of sodium amyloxide on tropine resulted in the formation of an equilibrium mixture of this base and pseudo-tropine, just as the action of alkali on pilocarpine or isopilocarpine results in the production of an equilibrium mixture of these two stereoisomeric bases (Jowett, Trans., 1905, 87, 794). This, however, is not the case, since the change is irreversible, no tropine being formed by the action of sodium amyloxide on pseudo-tropine. 

With the object, therefore, of definitely establishing the configuration of tropine and of pseudo-tropine, we have conducted experiments on the resolution of these bases, and some of their derivatives, by fractionally crystallising their salts with certain optically active acids. It may at once be stated that the results of these experiments point to the conclusion that both the bases in question are internally compensated compounds. The relation between them must, therefore, be of the nature of a cis-trans-isomerism, as concluded by Willstatter. (loc. cit.). Attempts were made to racemise tropine by heating the latter at high temperatures with hydrochloric acid, but these were unsuccessful. Source Barrowcliff 1909... 

Barrowcliff, M. Tutin, F. The Configuration of Tropine and Pseudo-Tropine, and the Resolution of Atropine Journal of the Chemical Society (1909) 1966-1977... 

Merck, F.E. Verfahren zur Darstellung von Pseudo-tropin aus Tropin durch elektrolytische Reduction 1900 DE 115517... 

Derivatives of Tropine and Pseudo-tropine. The configuration of the 3-OH group in the tropine part of the molecule has significant influence on the activity at the muscarinic receptor (Table 3.15). The derivatives of i//-tropine (pseudotropine, 3) are less active the activity ratio for the if/ compound relative to the isomeric tropine varies from 2 to 13, but more information is needed on this point. 

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 molecular structures of most of the calystegines are characterised by an equatorial hydroxyl group at carbon 3, which is the typical feature of pseudo-tropine (12). TRll and the reduction product pseudotropine (Figure 6) had been isolated from H. niger, but could not be integrated into the tropane alkaloid... 

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