Steroids obtaining

The stereochemistry of the product resulting from the reaction of a 17-keto steroid with ethylidenetriphenylphosphorane is different from that of the 17-ethylidene steroids obtained by dehydration of 17a-ethyl-17/ -hydroxy compounds, Wolff-Kishner reduction of A -20-keto steroids or by sodium-alcohol or sodium-ammonia " reductions of 17-ethynyl carbinols. These latter products have generally been assumed to possess the trans configuration (C-21 methyl away from the bulk of the ring system) because of anticipated greater stability. The cis configuration for... 

Withanolides. Withanolides are Cis-steroidal lactones that are isolated from the Solanaceae plant family. Withanolides are characterized by an ergostane-type skeleton, the Cl 7-side chain of which is transformed into a six-member lactone ring. The withanolides and the related crgostancs arc tile only known natural steroids obtained Ifum the same family dial have representatives with both a- and -orientations of the Cl7 side chain. 

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

Fig. 15.13) is an anti-inflammatory steroid obtained in one of the early approaches aimed at integrating ester moieties into steroid structures. Metabolism studies on fluo-cortolone revealed a number of oxidative and reductive metabolites in human urine (124), including fluocortolone-21-acid, an inactive metabolite. Synthesis and pharmacological evaluation of its different ester derivatives yielded fluocortin butyl (30, Vaspit, Novo-derm, Varlane), the butyl ester of a C-21 car-boxy steroid (125-128). The ester is an antiinflammatory agent of rather weak activity, and any portion absorbed systemically follow-ingtopical application is hydrolyzed into inactive species. 

Nuclear Magnetic Resonance. Ziircher s massive compilation of chemical shifts of 18-H and 19-H signals, and increments produced by structural features in the steroid nucleus, is augmented by the publication of similar data for 344 steroids obtained by microbiological hydroxylations, and subsequent transformations. The compounds are mainly 5a-androstane derivatives, and include hydroxy- and oxo-functions at almost all the ring positions, as well as their derivatives and polyfunctional compounds. Solvent shifts are also reported. A set of diagrams illustrates the profiles and chemical shifts of signals due to methine protons in the C/fOH system at all the main steroid positions. ... 

Steroids are animal hormones. However, their potential as pharmaceutical products could not have been realized while their manufacture depended on methods such as the extraction of estrone (13) from the urine of pregnant mares Cholesterol (14) and bile acids were better sources, but one of the initial steps in the requisite conversion involved oxidation with chromic acid, a transformation which was not efficient. Not until Marker realized in the early 1940s that progesterone (15) and testosterone (16) could be readily synthesized from diosgenin (17), a plant steroid obtained from a... 

Chlorotestosterone, 4-chloro-l 7fi-hyilroxyan-drost-4-en-3-ona an anabolic steroid obtained by partial synthesis from testosterone. Esters of 4-C. are used therapeutically, e.g. in convalescence, and for treatment of inflammation and tumors. 

Currently, steroids are still important in drug discovery, medicinal chem-istiy, and chemical biology. Many FDA-approved drugs are steroid based and are used to treat an assortment of medical ailments such as inflammation, allergic reaction, heart disease, cancer, and metabolic disease and have found applications in other important health-related areas that include contraception and fitness. Despite advancements in steroid synthesis that have resulted in synthetic strategies for their construction, the steroid-based drugs are obtained using semisynthesis from natural steroids obtained from plant and animal sources. 

The (20S, 22J )-steroid obtained in this way is an attractive intermediate for brassino-type steroids. 

H. Rosenkrantz and L. Zablow, Comparison of Infrared Absorption Spectra of Steroids Obtained on Solid Films and Mulls and in Solutions, Anal. Chem. 25, 1025, 1953. 

Calciferol is the anti-rachitic steroid obtained artificially. It was first regarded as being identical with vitamin D, and ergosterol was accepted as being the natural provitamin. However, in 1934, Waddell found that both irradiated cholesterol and cod-liver oil concentrates were more effective than calciferol, when given in equivalent dosage to rachitic chickens, and now it is believed that several different vitamins of the D type exist, including D, the anti-rachitic factor in natural liver oils, Dg, or calciferol, and Dg, the factor obtained from 7-dehydrocholesterol, which is its provitamin in crude cholesterol. 

The first section of this chapter is devoted to a statement of the problem of total synthesis and to a historical review. In the second section, the synthetic aspects of the formation, of the steroid skeleton and the introduction of functional groupings are considered. The third section is devoted to an analysis of certain problems connected with the formation of centers of asymmetry during total synthesis. Since the experimental material is summarized in detail in Chapters II-IV, in these sections, essentially, we give only references to the appropriate schemes of synthesis. Finally, in the fourth section of this chapter, the main features of the nomenclature of the synthetic steroids obtained by total synthesis are briefly discussed. 

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