Charney / Herzog Microbial Transformations of Steroids

A Handbook
1. Auflage 2014
ISBN: 978-1-4832-6155-3
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 742 Seiten

Microbial Transformations of Steroids: A Handbook aims to provide those who wish to use microbial transformations of steroids with a single source book starting from 1937 to the present. The handbook first offers information on the history of the microbial transformations of organic compounds, including earliest works on the study of nonsteroids and steroids; significance of discovery of anti-inflammatory action of cortisone; first hydroxylations and dehydrogenations; manufacture of natural and synthetic corticosteroids; and trends in research. The text then ponders on chemical classification of microbial transformations of steroids, as well as the role of enzymes in microbial transformations and the classes of reactions. The publication elaborates on the construction and use of the table. Topics include order of the table, nomenclature, description of the transformation leading to the product, yield, organism, and constants. The book also focuses on taxonomy and use of the table, including system of classification, specific notes on divisions of the table, and source of cultures. The handbook is a valuable source of data for readers interested in the microbial transformations of steroids.

Autoren/Hrsg.

Charney, William

Herzog, Hershel L.

Leseproben

CHAPTER I Introduction
Publisher Summary
Microbial transformations of organic compounds have been known in an empirical way from the dawn of history. In almost every civilization, primitive or advanced, man has practiced the fermentation of fruit, grain, or milk to obtain intoxicating and nourishing dietary factors. The rational application of these early techniques could come only after the scientific practice of organic chemistry and microbiology was begun. A sufficient understanding had developed by 1857 to provide the necessary background for the work of Louis Pasteur on the fermentation of sugar to lactic acid and ethanol. The most in the history of microbial transformations of steroids had been the synthesis of the hormones of the adrenal gland and of their more powerful and therapeutically selective synthetic analogs. Studies of the composition of steroids in bovine and other mammalian adrenal glands by Kendall, Reichstein, and Wintersteiner, and their respective collaborators, begun in the early 1930s, which led eventually to the isolation, characterization, and structural proof of cortisone. This chapter discusses the significance of discovery of anti-inflammatory action of cortisone, first hydroxylations and dehydrogenations, and manufacture of natural and synthetic corticosteroids.
Microbial transformations of organic compounds have been known in an empirical way from the dawn of history. In almost every civilization, primitive or advanced, man has practiced the fermentation of fruit, grain, or milk to obtain intoxicating and nourishing dietary factors. Evidence of wine production from as early as approximately 3000 B. C. has been found in excavations at Lachish and other sites.1 The rational application of these early techniques could come only after the scientific practice of organic chemistry and microbiology was begun. A sufficient understanding had developed by 1857 to provide the necessary background for the work of Louis Pasteur on the fermentation of sugar to lactic acid and ethanol. Herein was elucidated for the first time the concept that individual microbial species were responsible for discrete chemical alterations of selected substrates.2345 These experiments and their publication have been called “the birth of microbiology.”5 EARLIEST WORK - NONSTEROID
After Pasteur and until the end of the 19th century, few studies of the application of microorganisms to organic chemistry were carried out. None of these were of an intensive, systematic nature, which might have emphasized the broader possibilities of a fusion of the two sciences, 6, 7 although Brown recognized that such possibilities did exist. He gave individual examples of the oxidation of secondary alcohols to ketones and of primary alcohols to aldehydes and carboxylic acids. Beginning in 1896, Bertrand carried out extensive studies of the simple, oxidative process resulting from the action of Acetobacter xylinum on a series of polyhydric alcohols, and thereby established the generality of the illustrated scheme.8 9 10 As “Bertrand’s rule” was finally elaborated, it was shown that a pair of adjacent, cis, secondary hydroxyl groups, next to a primary hydroxyl group, suffice to establish conditions favorable for the oxidation.11 The reaction eventually became important for the conversion of sorbitol to l-sorbose,12 an intermediate in the manufacture of vitamin C. Dihydroxyacetone, which has been used extensively in recent times to tan human skin in vivo (for cosmetic reasons), can also be made on a commercial scale in the same way.13 A favored organism for these reactions is Acetobacter suboxydans. Following the work of Bertrand, the next major development in the field arose from the finding of Lintner and von Liebig14 that a fermenting yeast reduced furfur-aldehyde to the alcohol. Neuberg and his school explored the application of yeasts to a wide variety of substrates. Their studies are summarized in extenso by Fischer (F-245) and Stodola.15 EARLIEST WORK - STEROID
Steroidal substrates were used first, in 1937, by Mamoli and Vercellone (M-550, M-551), who began by extending the findings of the Neuberg school. They showed that fermenting yeast may be used to reduce 17-ketosteroids to 17ß-hydroxysteroids. This method had some passing importance in the manufacture of the male hormone, testosterone (M-543), and later of the female hormone, estradiol (W-1085), but was superseded by more convenient and efficient nonenzymatic procedures. Through the use of impure yeast cultures, Mamoli and Vercellone (M-538, M-540, M-542, M-552) discovered a useful class of sequential oxidation-isomerization reactions which they later attributed correctly to the action of the bacterial contaminants (M-553). A representative transformation of this type (including a hydrolysis step, as well) is the conversion of 3ß, 21-dihydroxy-5-pregnen-20-one 21-acetate to deoxycorticosterone by Corynebacterium mediolanum (Corynebacterium helvolum) (M-541, M-546). Schering (USA) employed a similar process to manufacture Reich-stein’s Compound S (17a, 21-dihydroxy-4-pregnene-3, 20-dione) for a time. It is now clear that nonenzymatic methods are more efficient for the synthesis of Compound S. Mamoli and his colleagues also recognized a class of bacterial reductions, which they attributed to an anaerobic bacterial species identified as Bacillus putrificus. Althrough this culture has since been lost, the same (5ß) and related (5a) reductions have been demonstrated with a variety of aerobic and anaerobic microbial species and have some academic interest since they parallel normal modes of mammalian metabolism of 3-keto-?4-steroids. Considered in the historical context, the timing of Mamoli’s pioneering application of microbial methods to the organic chemistry of steroids was logical. Just a few years earlier the correct structure of the steroid nucleus had been established. In 1935 testosterone was isolated from steer testis by Laqueur and was shown to be a powerful male hormone in a variety of animal tests. The structure was established by Butenandt and Ruzicka during the same year. The possibility of important medical application was on the horizon. We appreciate the element of inevitability in the development of microbiological transformations in the steroid field, arising as it did from the knowledge of the chemistry of yeasts developed by Neuberg and from the availability of 17-ketosteroid intermediates. The period from 1940-1949, following the early efforts of the Mamoli school, was rather quiet with respect to the further evolution of microbial transformations. Economic incentive for further study was absent because adequate nonenzymatic methodology had been devised for the synthesis of testosterone and related male hormone products, and estradiol. Also, the war disrupted scientific activity in Italy and Germany, where all the work had been done. Nevertheless, key observations which foreshadowed the subsequent explosive growth of the field were made. Horvath and Kramli (H-406) in 1947 reported the 7-dehydrogenation of cholesterol with Azotobacter sp. and in 1948 (K-474, K-475) they reported the 7-hydroxylation of cholesterol with Proactinomyces sp. These reactions, both novel at this time, were the first examples of what later proved to be the most important contributions of microbiology to steroid chemistry. There was no basis, at the time these observations were made, to appreciate their future import. Turfitt (T-1029, T-1030, T-1031, T-1032, T-1034) studied the use of steroids, as a sole source of carbon for microbial growth, and the steroid transformation products produced thereby. The key observations he made, which lay fallow until greater understanding of the field developed [cf. the work of Whitmarsh (W-1111) and particularly of Sih and his collaborators (AP-79, AP-83, AP-95) were that cholestenone and 3-keto-4-cholenic acid were transformed by Proactinomyces erythropolis, albeit to a very minor degree, into 3-keto-4-androstene-17ß-carboxylic acid. The idea which this illustrated was that cholesterol conceivably might be transformed by a microbiological degradative method into useful steroid entities of substantially lower molecular weight.16 SIGNIFICANCE OF DISCOVERY OF ANTIINFLAMMATORY ACTION OF CORTISONE
The most important chapter in the history of microbial transformations of steroids has had to do with the synthesis of the hormones of the adrenal gland and of their more powerful and therapeutically selective synthetic analogs. Studies of the composition of steroids in bovine and other mammalian adrenal glands by Kendall, Reichstein, and Wintersteiner, and their respective collaborators, begun in the early 1930’s, led eventually to the isolation, characterization, and structural proof of cortisone...