How it began
On October 15, 1951, at the laboratories of Syntex S.A. in Mexico City, the 26-year-old Mexican chemist Luis Miramontes completed the synthesis of norethindrone, also called norethisterone. He worked under Carl Djerassi, an Austrian-born American chemist, and the Syntex director George Rosenkranz, who wanted a progesterone that could be taken as a pill. Miramontes carried out the last step, adding a carbon-carbon triple bond.
Before it existed
Progesterone was already used in medicine, for example to prevent certain types of miscarriage, but it had to be injected to work. Syntex was a Mexican company that produced low-cost hormones from the wild Mexican yam Dioscorea mexicana, known locally as barbasco, which contains large quantities of a precursor that can be turned into several hormones.
How it works
Norethindrone is a modified progesterone made from the yam-derived precursor. It was designed to survive the digestive tract and to have more biological activity than progesterone itself, so it works when taken by mouth. Its chemical name is 19-nor-17-alpha-ethynyl testosterone.
Who pushed back
A year after Syntex reported norethindrone, chemists at the American firm Searle reported norethynodrel, which differs by the position of one double bond and is converted to norethindrone by stomach acid. Gregory Pincus, a co-developer of the first pill, chose Searle's compound, which became the first oral contraceptive approved by the US Food and Drug Administration in 1960. Miramontes remained little known outside Mexico.
Where it stands today
Norethindrone had the longer-lasting impact. Searle's compound is no longer marketed, while in 2018 norethindrone was still the 138th most prescribed drug in the United States. In 2001 the National Autonomous University of Mexico marked the 50th anniversary of the synthesis with Miramontes and Rosenkranz present.
