On this day in science, 10 August 1897, Bayer chemist Felix Hoffmann recorded the preparation of a chemically pure and stable form of acetylsalicylic acid (ASA), the compound that would later be marketed as Aspirin.
The chemistry of acetylation
During the summer of 1897, Hoffmann was exploring the modification of physiologically active molecules by introducing acetyl groups (CH3CO-), part of a broader medicinal-chemistry strategy aimed at altering properties such as potency and tolerability.
Bayer had already used related chemistry in developing medicines such as phenacetin, introduced in 1888.
From willow bark to salicylates
The medicinal properties of willow had been recognised for centuries.
During the 19th century, chemists increasingly unravelled the chemistry behind these effects. Salicin was isolated from willow, while Hermann Kolbe later developed a synthetic route to salicylic acid, helping make salicylates available on an industrial scale.
Salicylic acid was effective against pain and fever, but the relatively large doses then used, particularly for rheumatic conditions, could be difficult to tolerate.
According to the traditional story, Hoffmann was motivated partly by his father’s difficulty tolerating salicylates.
Acetylating salicylic acid produced acetylsalicylic acid, which proved sufficiently useful and tolerable for Bayer todevelop commercially.
It was launched under the name Aspirin in 1899.
Interestingly, acetylsalicylic acid itself was not completely new: earlier chemists had prepared the compound. Bayer’s important advance was producing a chemically pure, stable form suitable for pharmaceutical development.
The same chemistry, a very different outcome
Within weeks, Hoffmann also prepared diacetylmorphine by acetylating morphine.
The compound had actually been synthesized previously by C. R. Alder Wright in 1874, but Bayer later developed and marketed it under another now-famous name: Heroin.
Two molecules.
One medicinal-chemistry strategy.
Two profoundly different pharmaceutical legacies.
MBH/PS