The Nobel Prize in Chemistry 1939
Adolf Butenandt, Leopold Ruzicka
The following account of Butenandt's work has been made.
As recently as twelve years ago, very
little was known about the nature of the sex hormones. As regards
the oestrogenic, or follicle, hormone it was established that
extracts from certain organs, e.g. the ovaries and placenta,
bring about the characteristic oestrus phenomena in castrated
female rats. Only a few observations were available concerning
the stability and solubility of their active principles. Further
development in the chemistry of the oestrogenic hormones could
not take place until the purely biological discoveries by Allen
and Doisy in
1923 and by Aschheim and Zondek in 1927 had been made.
Butenandt made the first big step forward in clarifying the chemistry of the follicle hormone in 1929 in Göttingen, simultaneously with Doisy in the United States. Both workers succeeded in isolating from the urine of pregnant women a substance in crystalline form having oestrogenic effects. Butenandt named this substance folliculine, a designation which was later changed to oestrone. He established that its empirical formula was C18H22O2, and that it was an oxyketone.
Shortly after the discovery of oestrone, Marrian in London (1930) isolated from the urine of pregnant women a new hormone which he called oestriol. Butenandt confirmed Marrian's discovery and explained the relationship between the new substance and oestrone. The relation between sterols and oestrogenic substances which had been assumed on crystallographical grounds became probable from the chemical point of view only after Butenandt and Marrian had shown, independently of one another, that only three benzoide double bonds enter into the ring system of these substances.
In 1932, Butenandt was able, from observations made in spectral analysis, and especially on the basis of the then established correct formula of cholesterol to draw up the formulae of the chemical structure of oestrone and oestriol. But there remained the important task of proving the chemical structure of the ring system as assumed by Butenandt. By breaking down the oestriol molecule stage by stage Butenandt proved that both œstrogenic hormones contained a phenanthrene core. At the same time he was able to obtain the same dimethyl phenanthrene from etiobilianic acid, a transformation product of cholic acid. He had thus confirmed the close relationship existing between the follicle hormones on the one hand and the bile acids and sterols on the other.
The second important ovarian hormone, the corpus luteum hormone, was by various workers obtained in crystalline form from corpus luteum in 1931 and 1932. In 1934, Butenandt and Westphal succeeded in producing this hormone, which was given the name progesterone, in a chemically pure form. They also demonstrated its close relationship with pregnanediol, a physiologically inactive dihydric alcohol which Butenandt and Marrian had found independently of one another in the urine of pregnant women. In the autumn of 1934, Butenandt succeeded in converting pregnanediol into progresterone. The synthesis of this important pregnancy hormone from cholesterol was carried out by Butenandt in a simple way in 1939.
The merit of the chemical exploration of the testicular, or androgenic, hormones falls to Butenandt and Ruzicka in common. Butenandt was the first to tackle this problem, and it was only possible to work on it after biological research had found a quantitative test for the determination of these substances - the so-called capon comb test.
Butenandt started with male urine, or alternatively its chloroform extract - approximately 0.8 per thousand dissolved in chloroform. In the process of purification it proved that the male hormone behaved in many respects like oestrone; when he realized this, it made Butenandt's work considerably easier.
When the purification had been successfully accomplished, there presented for the first time a crystalline substance with the physiological properties of a male sex hormone.
Butenandt gave this substance the name androsterone and defined its composition as C19H30O2. It differs from oestrone only in the additional content of 1 methyl group and 5 hydrogen atoms. Butenandt drew up the full constitutional formula in 1934 on the basis of the formula of cholesterol.
Androsterone had been synthesized from epi-cholestanol by Ruzicka, but it soon proved to be not identical with the genuine male hormone from the testicles. For this reason it made a great stir when in 1935 Laqueur and his collaborators isolated from testicular extract a highly active hormonetestosterone.
The close relationship of testosterone to androsterone made it comparatively easy to clarify its chemical composition, and still in the same year 1935 Ruzicka and Butenandt were able, in the same way but independently of each other, to obtain testosterone from trans-dehydro-androsterone.
Butenandt, Ruzicka and others then produced from sterols various new substances which, when tested as male sex hormones, were found to be active in varying degrees.*
* Professor Adolf Butenandt was awarded half of the Nobel Prize in Chemistry for 1939, for his work on sex hormones. Owing to political conditions at the time, Professor Butenandt was prevented from accepting the prize. In 1949 he received the gold medal and the diploma.
The following account of Ruzicka's work has been made.
The higher terpenoids or polyterpenes,
which occur in great variety in the vegetable kingdom, were
originally the main subject of Ruzicka's investigations, and the
extremely difficult determination of their structure has been
made possible through his exceptional experimental skill. The
pioneering work of Ruzicka and his co-workers has led to thorough
investigations of a very large number of important
When studying the natural odorants occurring in musk and civet, muscone and civetone, little known until then, Ruzicka obtained fundamentally new and surprising results during the years 1924-1926. He discovered that the molecule of muscone as well as that of civetone contains one single ring of carbon atoms, the number of which was considerably larger than that in all hitherto known cyclic molecules, larger even than had been considered possible. During his investigations of these odora he synthesized many kindred macrocyclic compounds, and drew attention to the plant-physiologically remarkable fact that these could be prepared from natural fatty acids.
Many interesting relationships exist between the polyterpenes studied by Ruzicka and a series of physiologically and medicinally important groups of compounds, viz. the bile acids, the sterols and the sex hormones. Among the many interesting results obtained by Ruzicka and his collaborators with sex hormones, the preparation of compounds with the same action as male sex hormones is of signal importance. It is his merit that by establishing preparative methods for androsterone and testosterone the technical synthesis of these two hormones has been made possible.
Moreover, the numerous new related compounds prepared by Ruzicka have contributed fundamentally to our knowledge of the physiologically so very important sex hormones, thus creating a sound basis for future investigations *.
At a special ceremony in Zurich the prize was handed over to Professor Ruzicka by the Swedish ambassador Baron H. G. Beck-Friis on January 16, 1940, after a speech ending with the following words:
Professor Ruzicka. On behalf of the Nobel
Foundation and the Royal Swedish Academy of Sciences I convey to you
the most cordial congratulations - to which I may be permitted to
add my own - and at the same time express my hope that you will
be able to extend your research successfully to ever-increasing
fields in the service of mankind.
With this hope I have the honour to present you with the Certificate of the Nobel Prize for Chemistry for the year 1939 and with the Nobel Medal.
* Professor L. Ruzicka was awarded half of the Nobel Prize in Chemistry for 1939, for his work on polymethylenes and higher terpenes. Owing to the war conditions Professor Ruzicka attended the ceremonies later in 1945.
From Nobel Lectures, Chemistry 1922-1941, Elsevier Publishing Company, Amsterdam, 1966
Copyright © The Nobel Foundation 1939