The full structural formula of the complicated cocaine molecule, however, would have to wait over 30 years. Meanwhile, the commercial potential of cocaine was already being exploited.
Angelo Mariana, who was to become the world's first cocaine millionaire, was a Corsican from a long line of doctors and chemists. He moved to Paris in at a time when there was debate about the health-giving properties of coca and cocaine. After studying travellers' reports and the emerging literature, he became a habitual user. He found that the most bitter leaves were the most potent but the least palatable, and that steeping the leaves in Bordeaux wine led to the most agreeable way of preparing a 'tonic'.
With advertising, Vin Mariani became enormously successful, attracting celebrity endorsements from many notables of the day - including, allegedly, Queen Victoria, the Prince of Wales, the Shah of Persia, the writers H. Vin Mariani also claimed support from some doctors, including the young Sigmund Freud, then a Viennese neurologist. He advocated the tonic as a 'cure' for morphine addiction and to 'increase vitality' in a paper published in When he mentioned to colleague, Carl Koller, that cocaine caused numbness of the lips, eyes and mouth, Koller went on to develop its use as a local anaesthetic for eye operations.
With its role in anaesthesia, and widespread commercial and public interest, many chemists turned their attention to solving its structure. Some three years before Lossen had published his molecular formula, he had noted that if cocaine was hydrolysed by dilute hydrochloric acid it gave benzoic acid and another white crystalline material that analysed as C 9 H 15 NO 3.
He named this ecgonine, from the Greek ekgonos , meaning son of or descendant. Completing the equation leads us to conclude that the fragment is methanol, a fact that had to wait until for confirmation.
By this time chemical theory had advanced sufficiently for the 19th century chemists to conclude that ecgonine contained an hydroxyl group which could be esterified with benzoic acid and a -COOH group that could be esterified with methanol. The product from such a double esterification was cocaine. Just three years later, in , Alfred Einhorn showed that cocaine would form a quaternary ammonium salt on treatment with CH 3 I, a characteristic of tertiary amines.
Thus the nitrogen in the molecule is covalently linked to three carbon atoms, not hydrogen atoms. The hydroxyl group in ecgonine behaved like a secondary alcohol, producing a ketone ecgoninone, on oxidation. On gentle heating, this molecule lost its acid grouping to form the recognised product tropinone. Work on these two compounds was going on in parallel with the work on cocaine, often by the same research groups.
This meant that identification of the structure of any of either tropine, tropinone or ecgoninone would enable 'back-tracking' to deduce the structure of cocaine. Most researchers, in fact, focused on tropine, which had first been isolated in by Lossen.
That tropine might contain at least one ring structure was down to Adolf Baeyer. In he had shown that some alicyclic compounds could be dehydrogenated by heating them with zinc dust to give the corresponding aromatic ring species and thus help clarify their structure.
This indicated that part of the tropine molecule and thus part of the cocaine molecule contained a reduced or partially reduced pyridine ring bonded to two connected carbon atoms. In the same year Albert Ladenburg suggested structure 2 for tropine. And, in , this provoked Einhorn to propose a related structure for ecgonine, see 3. However, Carl Liebermann challenged these two structures because he could oxidise both ecgonine and tropine to tropinic acid.
Although this product was still of uncertain structure, it maintained both the ring system and the N-CH 3 grouping but, crucially, contained two -COOH groups. Oxidation of Einhorn's and Ladenburg's molecules would yield corresponding products that only contained one such exocyclic carboxylic acid group. So, in , Liebermann came up with his own versions of tropine 4 and ecgonine 5. Following on Liebermann's heels, Georg Merling suggested two less strained versions of tropine, see 6 and 7.
These and the subsequent structures are written as 'semi three dimensional' structures, though at the time the chemists drew their molecules as planar structures. He adapted Merling's ideas to incorporate this grouping with the carbonyl reduced to CHOH and proposed several structures for tropine, including 8 and 9.
This ruled out structure 9 since the maximum carbocyclic ring that this could yield would only contain six carbon atoms. In fact, structure 8 was the correct formula for tropine and he went on, in , to deduce the structures of ecgonine 10 and cocaine Two tasks remained - confirmation of the structure in two and three dimensions.
If the synthesised target matched the natural product, then the formula could be guaranteed. To complete the three dimensional picture, it was necessary to establish the configurations of the chiral centres within the molecule. This work was done by E. Coca sustains the system in an extraordinary manner under fatigue.
William Lyle, July 28, ; Photographed with 2 coca extract or cocaine bottles and a lozenge tin SydneyPlus Records: aiuy, aiuz, aivb. Title: Standardized fluid extract coca leaves, U. Note Type: Physical Description Notes: Amber glass bottle with a cork stopper; The neck of the bottle measures approx 3 cm in height; The opening is approx 1. Erythroxylacae [new line] Synonyms — Huanuco coca and Truxllio coca.
Anodyne and antispasmodic. It is a powerful nervous stimulant and increases the power of the muscular system to sustain fatigue. It contributes to mental cheerfulness and has been used in the treatment of opium habit, in which, however, it has no value except to antagonize certain heart symptoms. It should, in such cases, never be used as a regular remedy. Chloral is the most direct antagonist. Coca leaves.
William Lyle, July 28, ; Photographed with 2 coca extract or cocaine bottles and a lozenge tin SydneyPlus Records: aiuy, aiuz, aiva. One very popular drink, a wine called Vin Mariani, was endorsed by popular actors, writers, artists, physicians, and even popes.
Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information. Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies.
It is mandatory to procure user consent prior to running these cookies on your website. Cocaine was the first local anesthetic for regional anesthesia. Regional anesthesia involves numbing only part of the body by injecting local anesthetics into or near nerves, where they interrupt the transmission of pain signals to the brain. Cocaine is a derivative of a plant native to South America, Erythroxylon coca , or coca for short. The cultivation of the plant pre-dates the Incan civilization.
Long before the arrival of European explorers, coca was used by indigenous peoples of South America as a remedy for a number of health conditions, including headaches. In , a German chemist, Albert Niemann extracted the active substance from coca leaves and named it cocaine. However, it wasn't until that it became widely known as a local anesthetic. In that year Dr. Karl Koller , a German ophthalmologist, announced his successful use of cocaine as a topical anesthetic for eye surgery.
In Europe and the United States there was an immediate surge of experimentation with cocaine, leading to revolutionary developments in regional anesthesia as well as new surgical procedures. Corporate Author: C. Title variation: Alt Title Title: Boehringer muriate of cocaine bottle.
Publisher: Mannheim, Germany : C. But it was finally Carl Koller who, in , empirically demonstrated the benefits of cocaine use in medicine, most of all in ophthalmology. Subsequently, within a couple of months, the medical world learnt about and got interested in the use of cocaine for local anaesthesia. William Stewart Halsted and his collaborator Richard John Hall began their own research on cocaine injections. Eventually they developed the nerve and regional blocking techniques.
0コメント