Pharmacist Theodor Salzer (1833-1900) and the discovery of bisphosphonates.
Herbert Fleisch, the father of the therapeutic use of bisphosphonates in modern medicine, repeatedly stated in his numerous reviews that bisphosphonates were first synthesized 1865 in Germany by the Russian chemist Menschutkin. He was wrong on two counts. Had Menschutkin synthesized bisphosphonates, as he was a student of Wurtz at the time of the "synthesis", the birthplace of the substances would have been France and not Germany; but he did not. By reacting phosphorous acid with acetyl-chloride he obtained derivatives of pyro-phosphorous and pyro-phosphoric acids (P-O-P backbone) and not bisphosphonates (P-C-P backbone). The discovery of the first bisphosphonate occurred indeed in Germany but some thirty years later and not without some drama. First 1894 the pharmacist Theodor Salzer (1833-1900) described an impurity contained in commercially available phosphoric acid but failed to identify it as acetodiphosphoric acid, a bisphosphonate. 1896, an undergraduate student, Hans von Baeyer working in Munich at the Royal Academy of Sciences in the chemical laboratory of his father Adolf (the 1905 Nobel Prize laureate and discoverer of the barbiturates) synthesized an unknown substance which his famous father summarily rejected as some "Dreck" or impurity. Only due to the tenacity of young Hans work on the matter was continued and the paper describing the synthesis published a year later. The correctness of the chemical structure of the compound as assumed by von Baeyer (and his Ph.D. supervisor Hofmann) was confirmed 1901 by Heidepriem, a Ph.D. student of Hofmann. This short report attempts to shed some light on the life of the lesser known pharmacists and chemists involved in the synthesis of the first bisphosphonate, focusing on Salzer, Heidepriem and von Baeyer.
Florida International University (FIU), Herbert Wertheim College of Medicine (HWCOM), University Park, Miami, 33199 FL, USA. georg.petroianu@fiu.edu
G A
GA
Petroianu
D002621:Chemistry / Q000266:history; D004164:Diphosphonates / Q000138:chemical synthesis / Q000266:history* / Q000627:therapeutic use; D000077406:History of Pharmacy; D049672:History, 19th Century; D010595:Pharmacists
D004164:Diphosphonates