Tropeines

FLUORINECOMPOUNDS,ORGANIC - FLUORINATED AROMATIC COMPOUNDS] (Volll) (m-Hydroxybenzoyl)tropeine [52418-07-2]... 

The names, formulae and structures of these alkaloids are given in the following table. The esters of tropine or -tropine are known as tropeines or -tropeines respectively. The first eleven items in the table are sometimes called the solanaceous alkaloids, but they are not the only alkaloids, or even the only type of alkaloid, found in the botanical family Solanaceas. They are also sometimes referred to as the mydriatic alkaloids though other alkaloids also exert this action. 

This synthetic tropidine was converted into bromodihydrotropidine by hydrogen bromide in aeetie aeid, and the solution heated with 10 per cent, sulphurie acid at 200-10°, when it passed into -tropine,and, sinee this may be partially converted into tropine by oxidation to tropinone and reduction of the latter by zinc dust and hydriodic acid, this series of reactions affords a complete synthesis of tropine and of the tropeines. Combining the formula given above for tropine with that of tropic acid, atropine and hyoscyamine are represented as follows ... 

The importance of tropinone as a possible starting-point for the production of the therapeutically valuable alkaloids atropine, hyoscyamine, cocaine, tropacocaine and the artificial tropeines (p. 73) led Robinson to consider the possibility of preparing this substance by a simple method. Starting with the idea that the formula for tropinone (XXX) may be regarded as made up of the formulae of the residues of succindialdehyde (XXVII), methylamine (XXV III) and acetone (XXIX), he found that a mixture of these substances in water, when allowed to stand for thirty minutes produced tropinone, which could be detected by means of its characteristic dipiperonylidene derivative (bright yellow needles, m.p. 214°). 

The formula of hyoscine may now be written as tropylscopine (tropylscopeine by analogy with the tropeines) and the relationship of scopine to oscine, teloidine and tropine, the other principal hydrolytic products of this group, are shown by the following formulae. 

Tropeines or (ji-tropeines Benzoyltropine tropacocaine (benzoyl-tfi-tropeine). 

Tropacocaine (Benzoyl-ili-tropeine), CuHj gOgN, was discovered by Giesel in Java coca leaves and has since been found in Peruvian coca. Its preparation from the former source has been described by Hara and Sakamoto, It crystallises in needles, m.p. 49°, is insoluble in water, but soluble in alcohol, ether or dilute ammonia and is generally prepared by benzoylating /t-tropine, and purified as the hydrochloride. Its alcoholic solution is alkaline and optically inactive. The hydrochloride forms needles, m.p. 271° (dec.), and the hydrobromide leaflets. The aurichloride separates in minute yellow needles, m.p. 208°, from hot aqueous solutions the picrate has m.p. 238-9°. When heated with hydrochloric acid or baryta water the alkaloid is hydrolysed to benzoic acid and -tropine. ... 

Mandelyl-ip-tropeine ( 4-homatropine), C gHaiOaN, is a thick uncrystallisable oil. Tropyl-iji-tropeine, 7112303, crystallises in colourless needles, m.p. 86°. 

These results indicate that in these new ester mydriatics, the structural factors, which influence the development of this type of pharmacological action are similar to those made evident by the chemical investigations of Jowett and Pyman and the pharmacological work of Marshall, Dale, Laidlaw and Cushny on the tropeines. The nature of the basic component is obviously important since mydriasis is produced by simple bases such as ephedrine. As regards the nature of the esterifying acid, Jowett and Pyman drew the following conclusions — ... 

I. Tropeines of aliphatic acids exert no mydriatic effect. 

II. The replacement of the benzene residue by that of pyridine in the acyl group of a mydriatic tropeine does not cause the activity to vanish. 

III. In tropeines containing a disubstituted benzene ring, those in which the replacing groups occupy the pam-position have the least mydriatic action thus 0- and m-hydroxybenzoyltropeines are active, but not the p-isomeride. 

IV. No generalisation as to the relation between the mydriatic action and chemical constitution of the tropeines can be made which will explain the observed facts. 

Stereoisomerism in either the alkamine nucleus or the acyl residue has a considerable effect on the pharmacological action of the tropeines and cocaines. Differences in activity of tropine and i/i-tropine and their benzoyl derivatives have been mentioned already, and there seems to be a consensus of opinion that the i/i-cocaines (alkyl- or aryl- acyl esters of 0-ecgonine) are less toxic and more potent local anfesthetics than the corresponding cocaines, derived from 1-ecgonine. ... 

Cushny has compared the action of d- and Z-hyoscyamines with that of atropine, and of d-homatropine with that of dZ-homatropine in antagonising the action of pilocarpine, and finds that the order of activity of the first three is in the ratio 1 40 20, and of the second two in the ratio 4 2-5. He drew attention also to the important influence of the acyl radical in the tropeines, which exercises the maximum effect when it is a hydroxyalkyl aromatic residue and is laevorotatory and in illustration of this point gives the following table of relative activities on the basis of capacity to antagnonise pilocarpine in the salivary fistula dog —... 

Tritopine. See Laudanidine. Tropacocaine, 62, 64, 79, 100 pharmacological action, 106 Tropane, 87, 108 Tropane group alkaloids, 64, 776 pharmacological action, 105 Tropeines, 73, 79, 81 Tropehone, 80 Tropic acid, 72... 

As for the GABAa receptor, positive modulators that enhance glycine receptor activity have been identified. These include alcohols, neurosteroids, tropeines and the divalent metal ion Zn2+, which is highly enriched in some types of excitatory neuron [27], Zn2+ release from such neurons may potentiate glycine receptors at neighboring inhibitory synapses and thus facilitate inhibition following strong excitation. 

The mass spectroscopic fragmentation of phyllalbine gave essentially the same species as did atropine and other tropeines studied by Djerassi et al. (Safi) and controlled by the use of deuterated samples. This will be dealt with further in Section VI. 

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. 

The rates of hydrolysis of epimeric benzoyl and p-nitrobenzoyl- -tropeines and those of their methiodides have been determined (9). 

Since tropine esters show smaller rates than -tropeines and since boat conformations of the six-membered ring are postulated, these facts were attributed to the hydroxyl group hindered in the former case by a neighboring N-CH3 group. Thus configurations opposite to those established by chemical means have been ascribed to the epimers. These views have been revised and corrected by the same workers (10). 

Typical physiological effects exerted by tropane bases hitherto known are essentially as follows (l) mydriatic, i.e., parasympathetic blocking, (2) anesthetic, (3) stimulating the central nervous system. Recently (4) ganglion blocking, i.e., curare-like activity, has been detected in some synthetic tropeines. 

Tropacocaine. exo-ti-Methyl-8-azabicyclo[i.2.1 ]-octan-3-ol benzoate laltt5all-iropan-30-ol benzoate ben-zoylpseudotropeine benzoyl-d -tropeine pseudotropine benzoate -tropine benzoate tropacaine. mol wt... 

Apoatropine results from the dehydration (27) (nitric acid, sulfuric acid, acetic or benxoic anhydrides, or phosphorus pentoxide) of atropine. It was proved to be atropyltropeine, for it results from the repeated evapo-ratiiHi of a hydrochloric acid solution of tropine wdth atropic acid (22) or by the action of tropine with o(-phenyl-/3-chloropropionyl chloride and elimination of hydrogen chloride from the primary tropeine (158). 

The hydroxyl of pseudotropine has been esterified with various aliphatic and aromatic acids. These esters are known as the pseudotropeines. Of these, tiglylpseudotropeine is known under the name tigloidine and has been isolated from Duboisia myoporoides R. Br. (222), while benzoylpseudo-tropeine or tropacocaine has been isolated from the leaves of a species of coca grown in Java (120). Tropacocaine (120) and the pseudotropeines (211), unlike atropine and the tropeines, show no mydriatic properties. 

Picrate 218 Tropacocaine (see Benzoylpseudo-tropeine) Tropane (see also Scopolane and Hydro tropidine) Oil, d 4 = 0.9259 172... 

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