Synthesis of Aspirin and Heroin

The story of these two medicines speaks of the great desire and efforts of chemists, at the end of the 19th century, to synthesize new substances that would be used for treatment. Until then, only active principles isolated from drugs or substances obtained synthetically, with the same chemical structure as known active principles, were used. After a certain time, the conditions for the synthesis of new drugs were created. One of the ways was the modification of the chemical structure of the already known active principles, and the other was the synthesis of new substances by chemical reactions of then available organic compounds.

Aspirin (acetylsalicylic acid) is one of the greatest pharmacological achievements of the 20th century. and the most widely used drug worldwide. Vjekovi su prošli od otkrića ljekovitih svojstava preteče ovog lijeka do razvoja savremenog farmaceutskog proizvoda. Iako je Aspirin sintetisan 1897.godine, istorija upotrebe salicilne kiseline datira još od prije 3500 g.p.n.e., kada su Sumerani i Egipćani a kasnije čuveni ljekari drevne Grčke i Rima upotrebljavali koru vrbe protiv bola, povišene temperature i određenih upalnih procesa. U 18. vijeku (1763. g) prvi put su naučno potvrđena dejstva osušene kore vrbe. Početkom 19. vijeka (1828. g) izvršena je ekstrakcija salicina kao aktivnog sastojka, a zatim, 10-ak godina kasnije, naučnici su uspjeli da hemijskim reakcijama salicin prevedu u salicilnu kiselinu. Nakon otkrivene hemijske strukture (1859.g.), salicilna kiselina je uspješno dobijena i sintetskim putem. Uvođenje salicilne kiseline kao lijeka u terapiji prouzrokovalo je pojavu neželjenih efekata, koji su se manifestovali u vidu jake iritacije želuca, mučnine i povraćanja. Ovi neželjeni efekti su predstavljali veliki problem kod osoba koje su svakodnevno koristile ovaj lijek, što je ograničavalo njegovu primjenu.

German chemist and pharmacist Felix Hoffman, after successfully completing his doctorate, begins his working life at the Bayer company. Hoffman's father had rheumatoid arthritis accompanied by severe pain, and his already deformed joints made it very difficult to function. He used salicylic acid, which he had a hard time tolerating because of the side effects. His father's suffering motivated Hoffmann to conduct independent research on the synthesis of new drugs that would be safe for the treatment of everyday pain. He experimented the most with the acetyl group, adding it to various substances in the hope of improving their effects or reducing toxicity. It was stimulated by the synthesis of phenacetin, the first synthetic drug of the Bayer company, which was obtained by acetylation of the by-products of the production of synthetic dyes. Hoffman hypothesized that salicylic acid would be more tolerable if it were more soluble in stomach acid. To achieve this more soluble form, he replaced the hydrogen from the hydroxy group on the benzene ring of salicylic acid with an acetyl group. This reaction produced acetylsalicylic acid with the desired therapeutic effects and mild, tolerable side effects.

After studies confirmed the effectiveness and safety of acetylsalicylic acid, the Bayer company began production of a new drug called Aspirin, whose name comes from acetyl ("A") and Spirea, the name of a genus of shrubs that was the source of salicylic acid. Since then, Aspirin has become synonymous with the Bayer company and at the same time the most famous drug in the world. Its importance has not diminished even today, on the contrary, different forms of Aspirin have been developed and the indications for the prevention of diseases of the heart and blood vessels have been expanded. Aspirin will probably be the medicine of the future because research is underway on its effect on dementia, cardiac diseases and cancers.

Only 15 days after the synthesis of Aspirin, Felix Hoffmann performs the acetylation of morphine alkaloids. Morphine is the first isolated alkaloid with a strong analgesic effect. However, the use of morphine is limited because it leads to addiction. Hoffmann had the goal of synthesizing a substance that would retain its therapeutic effect without manifesting addiction. By acetylating morphine, he obtained diacetylmorphine, whose effect he tested on animals and volunteers from the Bayer company. After the application, the Bayer workers felt "heroic, heroic" (heroisch) after which they named this substance Heroin. The first results of testing the effectiveness and safety of Heroin were so promising that it was considered a miracle drug. Indeed, it was more effective than morphine in pain therapy, so it was presented at the Congress of German Naturalists and Physicians (1898) as a safe, non-addictive alternative to morphine. Since 1899 Bayer produces large quantities of Heroin for 23 countries of the world, and the largest consumer was America, which had the largest number of morphine addicts, primarily veterans of the Civil War. Before Heroin's extreme addiction was recognized, it was widely marketed by Bayer and other companies to suppress coughs, relieve labor pains and severe war injuries, prepare patients for anesthesia, and control certain mental disorders. However, three years later, the first cases of heroin tolerance were reported, followed by numerous cases of strong addiction, which is why Bayer in 1913 ceases its production.