Luis E. Miramontes - Invention and Synthesis of Norethindrone

Invention and Synthesis of Norethindrone

The scientific contribution of Luis Miramontes is very extensive, includes numerous publications and nearly 40 national and international patents in different areas such as organic chemistry, pharmaceutical chemistry, petrochemistry and atmospheric chemistry and polluting agents. Among his multiple contributions to world science is the synthesis on October 15, 1951, when Miramontes was only 26 years old, of norethisterone (norethindrone), that was to become the progestin used in one of the first three oral contraceptives (combined oral contraceptive pills). By this reason, Luis Miramontes is considered by Lilia Miramontes to be its inventor. Carl Djerassi, Luis Miramontes and George Rosenkranz of the Mexican chemical company Syntex are listed on the patent for norethindrone as its co-inventors. Djerassi "is now known sometimes as the 'Father of the Pill'". The historians, nevertheless, agree that the invention, or the first synthesis, is the work of Djerassi, Miramontes, and Rosenkranz. For example, the Nobel laureate Max Perutz states that "On October 15th, 1951, the chemistry student Luis Miramontes, working under the direction of Djerassi and the director of the laboratory Jorge Rosenkranz synthesized the compound". Djerassi himself affirms that it was, in fact, Miramontes who conducted the very last step of the first synthesis of the compound: "On 15 October 1951, Luis Miramontes, a young Mexican chemist doing his undergraduate bachelor's thesis work at Syntex completed the synthesis of the 19-nor analogue of Inhoffen's compound—that is, 19-nor-17α-ethynyltestosterone or, for short 'norethindrone'—which turned out to be the first oral contraceptive to be synthesized. Lecture audiences are always intrigued when I display a slide showing the carefully dated and hand-written lab protocol of the very last step in that synthesis conducted by Miramontes, in which the elements of acetylene are added to impart oral activity." The scientific article reporting the synthesis of 19-nor-17α-ethynyltestosterone (norethindrone) has Miramontes as the second author. Finally, the very last step of the synthesis method was registered, on October 15, 1951, in page 114 of the Miramontes's personal laboratory notebook (signed).

In a 2006 essay in the FASEB Journal, the director of the Worcester Foundation for Experimental Biology said: "Another aspect of the Nobel Prizes that is a perennial topic of discussion concerns those discoveries, inventions, or advances that go unrecognized altogether. One is the birth control pill. I have just mentioned the Worcester Foundation for Biomedical Research, where pioneering work by Gregory Pincus and M. C. Chang was carried out in the 1950s that led to the first birth control pill. Pincus died in 1967—at the tragic age of only 63, but I doubt that a Nobel Prize would have been awarded in any case. The tributaries flowing into the development of the oral contraceptive were numerous and temporally distributed across two decades, going back to the extraction of a substance from the roots of a jungle plant by Russell Marker that was readily convertible to pregnanediol and then to progesterone in two steps, the subsequent chemical synthesis of progestins by Carl Djerassi, Luis Miramontes, and Alejandro Zaffaroni, and the discovery by Gregory Pincus and M.C. Chang at the Worcester Foundation that a compound sent to be tested by the G. D. Searle Pharmaceutical Company was, contrary to expectations, a potent anti-ovulatory progestin."