Tropacocaine

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°). 

Though the dialdehyde-tropinone synthesis does not succeed when the dialdehyde is replaced by a diketone, Blount and Robinson have shown that 1-methyltropinone (XXXV) can be obtained by the interaction of the keto-aldehyde, laevulinaldehyde. Me. CO. CH. CH. CHO, with methylamine and calcium acetonedicarboxylate, and from this by reduction to 1-methyl- -tropine and benzoylation, 1-methyl tropacocaine (b.p. 210°/15 mm. picrate, m.p. 163-4°) has been prepared. 

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. ... 

Tropacocaine (Benzoyl-i/r-tropine). This resembles cocaine in action, but produces local anaesthesia more rapidly and for a shorter time and causes little or no mydriasis. 

Whilst tropyltropine (atropine) is mydriatic, this property is of a low order in benz yltropine and is absent in benzoyl- -tropine. The former is a weak and the latter a potent local anaesthetic. This parallelism in the influence of the tropyl and benzoyl radicals in developing mydriatic and local aniesthetic action respectively, has been shown by von Braun and his co-workers to occur through an extensive series of hydroxyalkylamines in addition to tropine. Considerable modification may be made in the structure of tropine without impairing its capacity for yielding mydriatics anaesthetics. Thus von Braun, Muller and Rath found that e tropyl- and benzoyl-esters respectively of liomotropine (I) and of N-hydroxyalkylnortropanes (III) are comparable with atropine and tropacocaine (derived from tropine (II) and 4-tropine (II) ), respectively... 

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... 

The finding that the benzoyl ester, tropacocaine (14), possessed local anesthetic activity showed that the carbomethoxy group was not required for activity. 

Scheme 12. Kibayashi synthesis of pseudotropine (40) and tropacocaine (43). Reagents i, CCl4-EtOH (3 2), -20°C, 2 weeks ii, H2/Pd-C, MeOH iii, EtOCOCl or PhCH2OCOCl, aq Na2CO3,0°C - RT iv, SOCl2,py, CHC13,0°C - reflux , v, t-BuOK, C6H6-HMPA,0-5°C vi, LiAlH4, THF, reflux vii, (1) H2/Pd-C, MeOH, (2) HC02H, HCHO, reflux.

The use of ultraviolet irradiation to transform cocaine (98), 3a-benzoyloxytropane (14), and tropacocaine (43) to the corresponding N-demethylated products has been described 107). 

The various cocaine precursors and analogs seem not to have been tested for psychedelic activity. Cogentin (benzo-tropane) is hallucinogenic at a dose of about 4 mg. Synthetic compounds which may have activity are -pseudo-cocaine, tropacocaine, eccaine,... 

Hyoscyamine (duboisine) and the racemate atropine are mACh-R antagonists and a number of atropine derivatives also have this property, namely anisodamine (6P-hydroxyhyoscyamine), 7 (3-hydroxyhyoscyamine, hyoscine (6,7-epoxyhyoscyamine or scopolamine), benzoyltropein (tropine benzoate), littorine (tropine a-hydroxyphenylpropionate), tigloidine (pseudotropane tiglate) and tropacocaine (pseudotropine benzoate). The further derivatives apoatropine (a-dehydrohyoscyamine) and tropine are very toxic. 

During a screening of tropane alkaloids in Erythroxylum species from Southern Brazil, Zuanazzi et al. [83] identified a new alkaloid as 3p,6p-ditigloyloxynortropane. The five investigated species were also screened for MEG, tropacocaine, and cocaine. Tropacocaine and MEG were present in two plants but no cocaine was detected in any species. 

The second group comprises one alkaloid, tropacocaine, which is a benzoyl-pseudotropein. This alkaloid is important not merely because of its use in medicine but also because the base pseudotropine is isomeric with the base tropine found in atropine. 

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