Z-Ecgonine

When heated with mineral acids Z-cocaine is hydrolysed into Z-ecgonine (p. 96), benzoic acid and methyl alcohol and a like change takes place with baryta water. If the alkaloid is boiled with water, methyl alcohol is split off and a new base, benzoyl-Z-ecgonine is formed, which in turn can be hydrolysed by acids or alkalis into Z-ecgoninc and benzoic acid. Cocaine is, therefore, methylbenzoyl-Z-ecgonine. 

Z-Ecgonine, CgHigOgN. HjO. This substance was first obtained I Lossen as the final basic hydrolytic product of the action of acids c cocaine, and is obtainable in like manner from several of the alkaloii occurring with cocaine (see above). It crystallises from dry alcohol i monoclinic prisms, m.p. 198° (dec.), 205° (dry), [a]n — 45-4°, is soluble i water, sparingly so in alcohol, insoluble in most organic liquid Eegonine forms Salts with bases and acids the hydrochloride crystallis... 

The by-products in the crude extract from South American coca are removed by oxidation (below 5°) of a solution of the extract in 3% sulfuric acid with saturated permanganate solution. After filtration the base is liberated and crystallized from ether (239). The i-ecgonine, formed by hydrolysis of the esters in the preliminary extraction, may be converted to Z-cocaine by esterification (CHjOH) and benzoylation of the ecgonine methyl ester. A process has been developed whereby cinnamylcocaine and the truxillines are converted to Z-ecgonine methyl ester which in turn is converted by benzoylation to Z-cocaine. 

The stepwise hydrolysis is completed by boiling benzoyl-Z-ecgonine with dilute hydrochloric acid. 

The preparation of a number of 0-acyl derivatives of Z-ecgonine prove the presence of an alcoholic hydroxyl in this base. Furthermore, the original base may be dehydrated to anhydroecgonine, a product which is unsaturated towards permanganate and bromine. Dihydroanhydroecgonine... 

Cinnamyl-Z-ecgonine has been obtained by acylation of Z-ecgonine with cinnamic anhydride. Esterification of this cinnamyl-derivative with methanol gave cinnamylcocaine (103). After the physical properties of cinnamylcocaine had been established it was subsequently isolated from Java coca leaves (109) and from Erythroxylum monogynum Roxb. (77). It has been reported (77) that cinnamylcocaine is devoid of mydriatic and anaesthetic properties. 

Two more acyl derivatives of Z-ecgonine methyl ester have been isolated from Java and Peruvian coca leaves (104). The mixture of these two, at first known as cocamine, is present to the extent of 0.6% in these leaves. Hydrolysis (HCl) of cocamine gave methanol, f-ecgonine, and a separable... 

The recovery of i-cocaine from crude extracts has been increased by hydrolysis of the truxillines and cinnamylcocaine in methanolic sulfuric acid and benzoylation of the resulting Z-ecgonine methyl ester (125). 

Gray (20) has studied the effect of the replacement of the methyl ester of cocaine by other esters on anesthetic activity. The ethyl ester of benzoyl-Z-ecgonine, called cocethyline or methylcocaine, had been made earlier (21, 22) and had been found to possess typical cocaine-like action. 

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