A-Ecgonine

The configuration of Willstatter s a -cocaine has now been shown to be 3j8-benzoyloxy-3a-methoxycarbonyltropane by adopting the method of oxazine formation of the nor derivative of a -ecgonine methyl ester. This latter had been obtained from tropinone by the cyanohydrin route. Obviously the cyanide ion attacks the ketone from the a-direotion in contrast with metalloorganic compounds, which carry out nucleophilic attack from the nonhindered jS-position (130). 

A number of a-methyl-tropic esters of tropine and -tropine, together with their methiodides and decamethylene di-iodides, have been prepared (102) showing some atropine-like effect. Derivatives of a-ecgonine methyl ester have also been synthesized, e.g., benzilic and p-aminobenzoyl esters and decamethylene salts. a-Ecgonine itself, if injected, proved a potent local anesthetic agent (103), at variance with earlier findings (104). 

Cocaine is the oldest of the local anaesthetics. It is a central nervous system stimulant and is habit-forming. See ecgonine. 

Thus the ecgonin methyl ester fragment J ean elearly be reeognised only the link to the O atom still remains to be established. The attaehment of the O atom is identified by the large ehemieal shift value (Sfj = 5.59) of the proton on the same earbon atom. The parts A and J then give the skeleton K of eoeaine. 

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... 

Willstatter and Bode converted tropinone into (/(-ecgonine by treating sodium tropinone with carbon dioxide and sodium, when it yielded sodium tropinonecarboxylate. This on reduction with sodium in alcohol gave some dZ-i/i-ecgonine (p. 97), which on esterification with methyl alcohol and benzoylation yielded a dhcocainc. A simpler synthesis of ( -eegonine was achieved by Willstatter and Bommer, and reference is made on p, 80 to this and other processes, some of which have been protected by patents. These improvements having enabled the prepara-... 

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. ... 

Oxidation of ecgonine (2) by means of chromium trioxide was found to afford a keto acid (3). This was formulated as shown based on the fact that the compound undergoes ready themnal decarboxylation to tropinone (4)The latter had been obtained earlier from degradative studies in connection with the structural determination of atropine (5) and its structure established independently. Confirmation for the structure came from the finding that carbonation of the enolate of tropinone does in fact lead back to ecgonine. Reduction, esterification with methanol followed by benzoylation then affords cocaine. 

Alkaloids, e.g. cocaine, ecgonine, benzoylecgonine, ecgonine methyl ester 280 °C, 8 min or 260°C, 10-30 min Pale blue induced fluorescence (Xn > 390 nm, cut off filter), fluorescence amplification by a factor of 2 on dipping in liquid paraffin solution detection limits <10 ng. [13]... 

Fig. I Fluorescence scan of a chromatogram zone with 300 ng each of ecgonine methyl ester (1), cocaine (2), ecgonine (3) and benzoylecgonine (4) per chromatogram zone.

Phthalate esters are widespread contaminants and the dialkyl phthalates are hydrolyzed before degradation of the resulting phthalate (Eaton and Ribbons 1982), which is discussed in Chapter 8, Part 3. For dimethyl phthalate, dimethyl terephthalate, and dimethyl isophthalate only partial hydrolysis may take place (Li et al. 2005). Cocaine is hydrolyzed to benzoate and ecgonine methyl ester by a strain of Pseudomonas maltophilia (Britt et al. 1992). 

Dissolve 1 g coca paste in 10 ml 3% sulfuric acid, cool to 0° and add with stirring 8 ml 6% KMn04 and 10% sulfuric acid, 1 ml at a time over one hour. Let stand /a hour and add powdered oxalic acid with stirring until the precipitate which has formed dissolves. Extract two times with ether, basify the aqueous solution with NH4OH and extract four times with 18 ml ether. Dry and evaporate in vacuum the ether to get cocaine. The aqueous solution contains ecgonine, which can be converted to cocaine as shown below. 

Dissolve 8.66 g ecgonine in 100 ml methanol and bubble dry HCI gas through for Vi hour. Let stand two hours at room temperature and then reflux gently for V2 hour. Evaporate in vacuum, basify with NaOH and filter to get 8.4 g methylecgonine (V) (recrystallize-isopropanol). 4.16 g (V) and 5.7 g benzoic anhydride in 150 ml benzene with CaCI2 tube to exclude water and gently reflux four hours. Cool in ice bath, acidify with HCI and dry, evaporate in vacuum (or extract with ether, basify with NaOH, saturate with K carbonate and extract with CHCl3 dry and evaporate in vacuum) to get 6 g red oil which precipitates (VI) with addition of a little isopropanol. 

The Peruvian coca leaves, because of their richness, are commonly used in the extraction process as described in 1 or 2. When the dried coca leaves have a low cocaine content, the ecgonine process is preferred. Normally, it takes approximately 100 pounds of dried leaves to produce one pound of cocaine. 

As you can see, this is quite a chore. The coca leaves give ecgonine, which as you can see, is only a jump away from cocaine. If you can get egconine, then dissolve 5 7 g of it in 100 ml of ethanol and pass (bubble) dry HCl gas through this solution for 30 min. Let cool to room temp and let stand for another V/i hours. Gently reflux for 30 min and evaporate in vacuo. Easily the residue oil with NaOH and filter to get 8.4 g of methylecgonine, which is converted to cocaine as in the cocaine step above. 

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