Steroids early history

P. A. Lehmann, Early history of steroid chemistry in Mexico the story of three remarkable men , Steroids, 1992, 57, 403 108. 

This section describes the early history leading to creation of the steroid industry, provides an account of key processes used in the manufacture of the oral contraceptives and anti-inflammatories currently marketed in the United States and highlights the creation of diverse biological activities by molecular manipulation of the steroid molecule. The section concludes with an outline of a few of the synthesis challenges faced and overcome in the manufacture of betamethasone anti-inflammatories. 

For early history of the topic see Trost, B. M. The Juvenile Hormone of Hyalophoria Cecropia Acc. Chem. Res. 1970, 3, 120 and references cited therein. See also, Rees, H. H. Goodwin, T. W. Molting Hormones Biochem. Soc. Trans. 1974, 2,1027-1032. Karlson, P. Sekeris, C. E. Ecdysone, an Insect Steroid Hormone, and its Mode of Action Recent Progress in Hormone Research 1966, 22, 473 95. 

Treatment with steroids may initially evoke euphoria. This reaction can be a consequence of the salutary effects of the steroids on the inflammatory process or a direct effect on the psyche. The expression of the unpredictable and often profound effects exerted by steroids on mental processes generally reflects the personality of the individual. Psychiatric side effects induced by glucocorticoids may include mania, depression, or mood disturbances. Restlessness and early-morning insomnia may be forerunners of severe psychotic reactions. In such situations, cessation of treatment might be considered, especially in patients with a history of personality disorders. In addition, patients may become psychically dependent on steroids as a result of their euphoric effect, and withdrawal of the treatment may precipitate an emotional crisis, with suicide or psychosis as a consequence. Patients with Cushing s syndrome may also exhibit mood changes, which are reversed by effective treatment of the hypercortisolism. 

European Company to produce insulin and important suppliers of oestrone,274 Lederle,275 and Roussel Uclaf and Schering AG in Europe.276 Another development arising from this early research on steroids was Barton s pioneering studies in conformational analysis. The reminiscences include those by Fried on the discovery of the fluorosteroids at the Squibb Institute for Medical Research in New Jersey,277 and of studies of the biochemistry of steroid hormones linked to genetics and the history of cancer.278 Clearly, the problems of unravelling the complex mechanisms of steroid action have aroused considerable interest.279... 

An elevation of the partial pressure of carbon dioxide (Pco2) greater than 45 mm Hg suggests that bronchospasm is the most likely cause of hypercarbia therefore, bronchodilators should be used aggressively. If the patient has a prior history of clinical bronchospasm, steroids should be added immediately steroids should also be considered if the patient has a history of hay fever or eczema and obvious bronchospasm with the current exposure. Occasionally, positive pressure ventilation may also be necessary. Interstitial lung water (early pulmonary edema) may trigger bronchospasm in individuals who are otherwise hyperreactive (such as those with cardiac asthma). Steroids are not primarily useful in this circumstance. 

Bronchospasm is an early and prominent complication of chlorine exposure. Aggressive bron-chodilator therapy (a combination of adrenergic agent and theophylline) is appropriate. Steroids are used if the patient has a history of hyperreactive airways. Bronchodilators are used at least until the antibiotics are discontinued and there is no further evidence of clinical response (eg, as indicated by laboratory testing). Steroid doses should be tapered as rapidly as clinical circumstances warrant after the first 3 to 4 days of (uncomplicated) recovery. Superinfection may complicate prolonged steroid therapy. 

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 (1938). 

The history of cytochrome P450 (P450) really began with studies on the metabolism of drags, carcinogens, and steroids. The early research in these fields necessarily involved animal models, but the intent was always to imderstand the human systems in the context of the enzymes catalyzing the observed transformations. 

As mentioned earher, the history of P450 research can be traced to early studies on the metabolism of drags, carcinogens, and steroids. Application in these areas was remarkable in the period 1985 to present, and each area will be treated separately. Overall, the P450 field can be considered a model for how basic research can lead to important developments for human medicine. Defects in several of the P450s have been hnked to serious human diseases (Table 9.3). 

Deoxycholic acid was an important starting material for the early synthesis of cortisone and other cortical steroids. It was obtained principally from cholic acid by selective oxidation and subsequent Wolff-Kishner reduction. Cholic acid was obtained from beef bile which also contains substantial amounts of deoxycholic acid. The history of this period of steroid investigation is reviewed by Fieser and Fieser (1). 

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