1950

Cortisone

Edward Calvin Kendall (1886–1972), Philip Showalter Hench (1896–1965), Tadeus Reichstein (1897–1996), Percy Lavon Julian (1899–1975), Kenneth Callow (1901–1983), Lewis Sarett (1917–1999), Max Tishler (1906–1989), John Warcup Cornforth (1917–2013)

The complex steroid ring system was an excellent proving ground for synthetic chemistry, and the products were in great demand, so steroid chemistry and steroid biology were exciting fields for discovery during the 1950s. When American chemist Edward Calvin Kendall, American physician Philip Showalter Hench, and Swiss chemist Tadeus Reichstein discovered the structures of cortisone and the adrenal corticosteroids and realized their far-reaching effects on the body, their value as drugs became very clear. Indeed, cortisone was successfully tried early on to treat rheumatoid arthritis.

But synthesizing the steroids strained the abilities of industrial chemists. In the 1940s, American chemist Percy Lavon Julian found routes from soybean compounds, following up on Russell Marker’s yam-derived syntheses, and he later famously improved the cortisone route by avoiding a step using the highly toxic (and highly expensive) osmium tetroxide. In England, Australian-born chemist Sir John Warcup Cornforth and biochemist Kenneth Callow found a progesterone route for the drug firm Glaxo from compounds in the sisal plant.

Pharmaceutical company Merck’s early cortisone process (discovered by American chemist Lewis Sarett and requiring over thirty steps) probably set the contemporary record for the longest industrial synthetic route—one that would be tried only for a very high-value product. One intermediate was a bright red dinitrophenylhydrazone, similar to the compounds produced by Emil Fischer from carbohydrates and in Sanger sequencing from proteins. A widely told story has American chemist Max Tishler, Merck’s director of process chemistry, coming into a lab to find a red liquid spill and shouting, “I hope that’s blood!” In 1951, though, a team at pharmaceutical company Upjohn found that microbial cultures oxidized progesterone to a perfect starting material for cortisone. They stunned Mexican pharmaceutical firm Syntex with an order for ten tons of progesterone and competed with Merck’s cortisone chemistry, producing a drug that is still used to treat a wide array of conditions.

An old-fashioned assay for cortisone in blood samples, 1952. (Note the forest of separatory funnels.)