The period from late 1949 through 1951 was an extraordinarily productive one in steroid chemistry and especially so at Syntex S.A. in Mexico City. Two of the most important Syntex contributions--the synthesis of 19-nor-17 alpha-ethynyltestosterone (norethindrone) and of cortisone from diosgenin--are described from a historical perspective.
PIP: The pharmaceutical industry contributed more to the published record of steroid research during the 1950s than any industry has ever contributed before to any chemical subdiscipline. Syntex, a research-oriented company in Mexico city, contributed much of the publication of industrial research of steroids. Dr. Djerassi arrived at Syntex in 1949 as associate director of chemical research. He conducted partial aromatization studies leading him to the 1st synthesis of an oral contraceptive (OC) on October 15, 1951. This steroid was 19-nor-17 alpha-ethynyltestosterone, later called norethistrone or norethindrone. Syntex submitted the product to a commercial laboratory in Madison, Wisconsin, for biological evaluation. It was indeed the most active, orally effective progestational hormone at the time. Syntex applied for a patent in November 1951. In November 1954, clinical results of norethindrone used to treat various menstrual disorders and fertility problems was presented. G.D. Searle & Co. filed for a patent for the synthesis of the double bond isomer 13 of norethindrone called norethynodrel in August 1953. Acid or human gastric juice converts norethynodrel into norethindrone. Had it not been for Searle using norethindrone in its antimotion sickness drug, Dramamine, Syntex would have filed suit against Searle. Syntex sponsored contraceptive trials with norethindrone. Various incidents prevented Syntex from obtaining US Food and Drug Administration approval to use norethindrone for contraceptive indications before Searle obtained approval to use norethynodrel. By 1964, 3 companies including Syntex were marketing 2 mg doses of Syntex's norethindrone, the most widely used active ingredient in OCs. Dr. Djerassi also played a key role in the synthesis of cortisone from diosgenin, a chemical derived from Mexican yams. This synthesis was a more economical industrial route to cortisone than previous routes.