Direct Evidence for a Furtive State in the Degradation of Carbasalatum Calcicum

✍ Scribed by Philippe Ochsenbein; Michel Bonin; Olivier Masson; Denis Loyaux; Gervais Chapuis; Kurt J. Schenk

• Publisher: John Wiley and Sons
• Year: 2004
• Tongue: English
• Weight: 118 KB
• Volume: 43
• Category: Article
• ISSN: 0044-8249
• DOI: 10.1002/anie.200353007

✦ Synopsis

The soothing effects of the bark, leaves, and fruits of species of the Spireae genus were known in a mystical, intuitive manner to our most distant ancestors. [1] The knowledge was then formalized, compiled, and propagated throughout the world by the great physicians and pharmacologists, such as Hippocrates, Theophrastus, Dioscorides, and Galen. After this period, this blossoming area of therapeutics lay dormant for almost two thousand years and its renaissance only began in the early eighteenth century when the English pastor and naturalist Edward Stone published his case-study of the effect of willow bark on patients suffering from agues. Novel insights then followed in rapid succession: in 1838 the Italian chemist Rafelle Piria extracted the active component, salicylic acid (SA), in 1874 Hermann Kolbe published its total synthesis, and by 1899 three derivatives devoid of the unpleasant side effects of the pure acid had been discovered. The most useful of these, acetylsalicylic acid (ASA), turned out to be a wonder drug against a broad spectrum of aches: from fever and heart attacks through to inflammations and gout and nowadays is even used to prevent thromboses and embolisms. Recently, salicylates have also been reported to play a role in the reversal of obesity-induced insulin resistance. [2] However, since ASA is scarcely soluble in water (1 g in 300 ml), it deploys its beneficial effects only after having been attacked by the alkaline media in the duodenal region of the intestine. [3] During these reactions it can cause gastric disturbances in sensitive patients. This can be remedied by elaborating derivatives that are more soluble in water and therefore more easily assimilated in the digestive tract. [3,4] Indeed, improved water solubility and incorporation of biologically active transition metals such as Cu [5] and Zn [6] have often been jointly striven for. To date, about two dozen