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Luis E. Miramontes, ca. 1951.
Luis Ernesto Miramontes Cárdenas (March 16,
1925 – September 13, 2004) , was a Mexican chemist known as the co-inventor of the
progestin used in one of
the first two oral
contraceptives.
Miramontes was born at Tepic,
Nayarit. He obtained his
first Degree in chemical engineering in the Universidad Nacional Autónoma de México
(UNAM). He was founder researcher of the Institute of the Chemistry
of the same University, making research in the area of Organic Chemistry mainly. He was a
professor of the Faculty of Chemistry of the UNAM, Director and
professor of the School of Chemistry at the Universidad
Iberoamericana, and deputy Director of Research at the Mexican Institute of
Petroleum (IMP). Miramontes was member of diverse scientific
societies, such as the American Chemical Society
(Emeritus), the Mexican Institute of Chemical Engineers, the
National Institute of Chemical and Chemical Engineers, the Chemical
Society of Mexico, the American Institute
of Chemical Engineers and the New York Academy of
Sciences.
He died in Mexico
City in 2004.
Invention and
synthesis of norethindrone
Luis E. Miramontes signed laboratory notebook. October 15,
1951.
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, it is the synthesis on October 15, 1951, when Miramontes
was only 26 years old, of norethindrone, that
was to become the progestin used in one of the first two oral
contraceptives (combined oral
contraceptive pills). By this reason, Luis Miramontes is
considered by Lilia Miramontes to be its inventor.[1] 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'"[2].
The historians, nevertheless, agree that the invention, or the
first synthesis, is the work of Djerassi, Miramontes, and
Rosenkranz.[3][4] For
example, the Nobel laureate Max Perutz[5] 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."[6] The
scientific article reporting the synthesis of
19-nor-17α-ethynyltestosterone (norethindrone) has Miramontes as
the second author.[7]
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."[8]
Outstanding life and
recognition
Patent of the first oral contraceptive, elected to the USA
Inventors Hall of Fame.
- In 1985 he received the "Estado de Mexico"
Medal, in the area of sciences and arts; as well as a public
recognition from the government of the state of Nayarit, and an
academic recognition from the Technological Institute of Tepic.
- In 1992 the General Hospital of Zone no. 1, of the Mexican
Institute of Social Security, in Tepic, Nayarit, was named "Luis Ernesto Miramontes
Cardenas Hospital".
- In 1994 the Mexican Ministry of Health recognized his
scientific contributions, when installing the National Program on
Family Planning in Mexico.
- He received in 1998, on behalf of the government of the state
of Nayarit, the "Amado
Nervo" Medal.
Luis E. Miramontes (right) with Nobel Laurate
Mario
Molina, ca. 1995
- In 2000, the contraceptive pill was
denominated three times as one of the most important inventions of
the last 2000 years, by a group of outstanding personalities, that
included several Nobel
laurates[9].
- In 2001, at the 50 Anniversary of the synthesis of norethindrone, the UNAM and the Mexican Ministry
of Health, organized individual tributes to Miramontes and
Rosencraz.
- In 2003, norethindrone was considered one of the
most important 17 molecules that have influenced the history of
mankind[2].
- In 2005, the Mexican Academy of
Sciences, denominated the invention of Miramontes as the
Mexican most important contribution to world science ever.
- In 2009, the BBC of London
nominated him as one of the five most important Latin American
researchers of all the times[10]
- In 2009, The School of Chemistry of UNAM recognized him as one the
most successful and important scientist to have received a degree
from it[11]
- In 2009, The School of Chemistry of UNAM honoured him by naming
the 2009 year prize QUIMIUNAM after him.[12]
Luis E. Miramontes, Andres Manuel del
Rio (discoverer of vanadium) and Mario Molina,
Chemistry Nobel
Prize in 1995, are the three most important Mexican chemists of
all times.
Selected
publications related to his invention
- Mancera O; Miramontes L; Rosenkranz G; Sondheimer F; Djerassi
C. 1953 Journal Of The American Chemical Society 75
(18): 4428-4429 Steroidal Sapogenins .28. The Reaction Of Peracids
With Enol Acetates Of Delta-8-7-Keto And Delta-8-11-Keto Steroidal
Sapogenins[16]
- Djerassi C; Miramontes L; Rosenkranz G; Sondheimer F. 1954 Journal Of The American Chemical Society 76
(16): 4092-4094 Steroids .54. Synthesis Of
19-Nor-17-Alpha-Ethynyltestosterone And
19-Nor-17-Alpha-Methyltestosterone[18]
Patented
inventions
- Carl Djerassi, Luis Miramontes, George Rosenkranz (1956),
Delta 4-19-nor-17alpha-ethinylandrosten-17beta-ol-3-one and
process, United States Patent 2744122
- Carl Djerassi, Luis Miramontes (1956),
Cyclopentanophenanthrene derivatives and compounds, United
States Patent 2759951.
- Carl Djerassi, Luis Miramontes, George Rosenkranz (1956),
17alpha-methyl-19-nortesterone, United States Patent
2774777.
- Miramontes Luis E., Romero Miguel A, Ahuad Farjat Fortunato
(1959), Preparation of 6-methyl steroids of the pregnane series
from diosgenin, United States Patent 2878246.
- Miramontes Luis E., Romero Miguel A, Fritsche O,
Preparation of 6-methyl steroids of the pregnane series,
United States Patent 2878247.
- Miramontes Luis E. (1959), Procedure for obtaining
sapogenins from natural un-dried products, United States
Patent 2912362.
- Carl Djerassi, Luis Miramontes, George Rosenkranz (1959),
DELTA.4-19-NOR-17.alpha.-ETHINYLANDROSTEN-17.beta.-OL-3
ONE, Canada Patent CA
571510
- Miramontes Luis E., Romero Miguel A (1960),
12alpha-hydroxy-12beta-methyltigogenin and 12-methylene
steroids derived therefrom, United States Patent 2954375.
- Miramontes Luis E., Romero Miguel A, Ahuad Farjat Fortunato
(1961),
3beta-alkanoyloxy-6-methyl-5,16-pregnadien-20-ones, United
States Patent 3000914.
- Miramontes Luis E. (1961), Process for the production of
3beta-hydroxy-16alpha, 17alpha-epoxy-5-pregnen-20-one, United
States Patent 3004967.
- Miramontes Luis E. (1961), Resolution of sapogenin mixtures
and intermediate products, United States Patent 3013010.
- Miramontes Luis E. (1962), Hecogenin azine and
alkyliden-azinotigogenins, United States Patent 3033857.
- Miramontes Luis E., Fritsche Oscar, Romero Miguel A (1963),
DEHYDRO-OXYGENATED-6-METHYL-16.alpha.,17.alpha.-EPOXYPREGN-20-ONE-DERIVATIVES,
Canada Patent CA
673756.
- Miramonte, Luis E., Flores Humberto J (1968), Process for
isolation of solanum alkaloids from solanum plants, United
States Patent 3385844.
- Miramonte, Luis E. (1972), Process for the conversion of
exhaust gases of the internal combustion engines into harmless
products, United States Patent 3808805.
- Miramontes Luis E., Castillo Cervantes Salavador, Moran Pineda
Florencia M (1996), Catalytically active ceramic monoliths for
the reduction of leaded gasoline fueled engine pollutants and the
production thereof, United States Patent 5534475.
External
links
References
- Lara V. Marks. Sexual Chemistry: A History of the Contraceptive
Pill.372 pp. New Haven, Conn., Yale University Press, 2001.
- Carl Djerassi. Steroids Made It Possible. American Chemical
Society, Washington