Synthesis of steroid hormones

Conclusions Methods have been developed for preparing steroid hormones (including estrogens, anabolics, contraceptives, and provitamins of the D group), which are important in medicine and veterinary practice, and also insect ecdysis hormones, which are promising materials for use in combating insects that are harmful to crops. A scheme of total synthesis has been developed into a process flow plan and has been put into commercial use. The proposed paths of synthesis also offer the possibility of synthesizing numerous steroid compounds with greatly different types of structure; the properties of these compounds, particularly their physiological action, will be the object of future research.This article is published in accordance with the decision of the editorial board of the journal, July 19, 1980.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 2, pp. 299–317, February, 1982.     

Some heterocyclic sulfonyl derivatives

2,3-Diphenylpyrazine, 3,4-diphenylfurazan and 2-methyl-4,5-diphenyl oxazole react with chlorosulfonic acid to give the sulfonyl chlorides Ia, IIa, IIIa. The chlorides were condensed with nucleophiles to give thirteen derivatives. 4′,4″-bis-Dimethylsulfamoyl-2-methyl-4,5-diphenyloxazole (Illb) was oxidized with bromine to give 4,4′-bis-dimethylsulfamoylbenzil (IV), which by heating with ethylenediamine afforded the 4′,4″-bis-dimethylsulfamoylpyrazine (V). The spectral data of the various compounds are briefly discussed.     

Synthesis of 6,19-cyclopregnanes. Constrained analogues of steroid hormones

A procedure for the synthesis of 6,19-cyclopregnanes is described involving an intramolecular alkylation reaction of Delta(4)-3-keto steroids with a 19-mesylate in the presence of KOH in isopropanol. Three 6,19-cyclopregnanes were prepared (4, 5 ,9); in the rat, 6,19-cycloprogesterone (4) and its 21-hydroxy derivative 5 displaced [3H]-dexamethasone from glucocorticoid receptors, the former compound being more active. Both compounds did not compete with [3H]-aldosterone for kidney mineralocorticoid receptors nor with [3H]-R5020 for uterus progesterone receptors.     

The electronic structure of steroid hormones

Zusammenfassung Es werden erweiterte Hückel-Rechnungen an den Nebennierenrindenhormonen Cortisol, Cortison, Corticosteron, Aldosteron und an den zwei synthetischen Verbindungen Prednison und Dexamethason durchgeführt. Die Gesamtenergie, die Einelektronenenergien, die Ergebnisse der Mullikenschen Populationsanalysen (Nettoatomladungen, Überlappungspopulationen, Außenelektronen-ladungen) und die Dipolmomente werden mitgeteilt und diskutiert.

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The electronic structure of steroid hormones2. The adrenal cortex hormones

Extended Hückel calculations have been carried out on the adrenal cortex hormones cortisol, cortisone, corticosterone, aldosterone and on the synthetic compounds prednisone and dexamethasone. Total energies, orbital energies, the results of Mulliken population analyses (gross charges, overlap populations, frontier electron densities), and dipole moments are presented and discussed.

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Ich danke dem Personal der Abteilung Informatik Rechnerbetrieb des Fachbereiches Kybernetik der Technischen Universität Berlin für die Durchführung der Rechnungen auf der IBM 360/67.     

Research in the field of heterocyclic chemistry. XL. Organic acids as intramolecular condensing agents for arylamide hydroxy acids

It is shown that the basic properties of arylamides of diarylglycolic acids are determined not only by the nature of the aryl radicals of the acid part of the molecule, but also by the extent to which hydrogen atoms of the amino groups are substituted. Formation of carbonium salts of arylamides is considerably influenced by the nature of the solvent. Intramolecular condensation of tertiary arylamides of 4, 4-dimethoxy- and 4, 4-dimethylbenzylic acids gives a number of new 1-alkyl (aryl)-3, 3-diaryloxindoles. Ethyl N-n-propyl- and N-isobutyloxanilate and N,N-diethylamide-4, 4-dimethoxybenzylate are described for the first time.For part XXXIX see [1].     

High-performance liquid chromatographic analysis of steroid hormones

In the present work, a practical, rapid, reliable and isocratic reversed-phase high-performance liquid chromatographic (HPLC) method is described for the qualitative and quantitative analysis of estriol, estradiol-17 beta, estrone, testosterone, and progesterone. Chromatographic separation is complete in 16 min using a mobile phase of 50% acetonitrile (v/v) in water. The order of elution is estriol, testosterone, estradiol-17 beta, estrone, and progesterone; retention times are 2.5, 5.5, 5.6, 6.9, 16.3 min, respectively. Absorbance maxima of individual steroids is the limiting factor in quantitative determination. The recommended wavelengths for UV monitoring are E3 214, E2 280, T 254, E1 214, and P4 254 nm.     

Derivatisation of steroid hormones with t-butyldimethylsilyl imidazole

An efficient procedure for the derivatisation of hydroxyl and alpha,beta-unsaturated ketonic steroids using t-butyldimethylsilyl imidazole is described. The conditions which employ potassium acetate as a basic catalyst result in quantitative formation of BDMS ethers and greater than 96% yield of BDMS-enol ethers. Various mechanisms involving the catalysed and uncatalysed reactions of t-butyldimethylsilyl imidazole with alcohols and enols are also discussed. The mass spectra of the BDMS-enol ethers, in contrast to the BDMS ethers, are dominated by an intense molecular ion, which facilitates the quantitation of these derivatives in biological samples. An example of the method is shown by the determination of 4-androstene-3,17-dione in urine using a stable-isotope internal standard.     

Recent advances in the analysis of steroid hormones and related drugs.

The development during the last 15 years and the state-of-the-art in the analysis of bulk steroid hormone drugs and hormone-like structures and pharmaceutical formulations made thereof are summarized. Other steroids (sterols, bile acids, cardiac glycosides, vitamins D) as well as biological-clinical aspects and pharmacokinetic and metabolic studies are excluded from this review. The state-of-the-art is summarized based on comparisons of monographs in the latest editions of the European Pharmacopoeia, United States Pharmacopoeia and the Japanese Pharmacopoeia. This is followed by sections dealing with new developments in the methodology for the fields of spectroscopic and spectrophotometric, chromatographic, electrophoretic and hyphenated techniques as well electroanalytical methods. The review is terminated by two problem-oriented sections: examples on impurity and degradation profiling as well as enantiomeric analysis.     

Some heterocyclic sulfonyl chlorides and derivatives

The syntheses of 4- and 5-chlorosulfonylfuran-2-carboxylic acid (Ia,IIa), 4-chlorosulfonylfuran-2-carboxamide (Ib), 3,5-dimethylpyrazole and isoxazole-4-sulfonyl chlorides (IIIa,IVa) and 2,4-dimethylthiazole-5-sulfonyl chloride (Va) are described. The sulfonyl chlorides were converted into a range of amides, hydrazides and azides. Condensation of the sulfonohydrazides with β-dicarbonyl compounds, gave the corresponding β-ketohydrazones (VII), which, with the exception of the derivatives (VIIe,f,g,i), were converted to the sulfonylpyrazoles (VIII). The structures and spectral data of these compounds are briefly discussed. The reaction of the sodio derivative of acetylacetone with thiophene-2-sulfonyl chloride (VIc) gave 3-(thiophene-2-sulfonyl)pentane-2,4-dione (XII), which with hydrazine gave 4-(thiophene-2-sulfonyl)-3,5-dimethylpyrazole (XIII). However, the analogous reaction with thiophene-2-sulfonohydrazide (VIa) failed to give the expected 1,4-bisthiophenesulfonylpyrazole.