Derivatives of the androstane series

Conclusions 1. The synthesis of 17-hydroxyandrostano[3,2-c]pyrazole and of cholestano[3,2-c]pyrazole has been effected by the reaction of the corresponding 2-hydroxymethylene-3-oxosteroids with hydrazine hydrate.2. The mechanism of the formation of these pyrazoles has been studied. It has been shown that the reaction takes place in two stages, regardless of the substituent at C₁₇ of the steroid molecule, with the formation of the 2-hydroxymethylene-3-hydrazone and its dehydration to form the pyrazole derivative.Khimiya Prirodnykh Soedinenii, Vol. 6, No. 1, pp. 31–33, 1970     

Synthesis of derivatives of the androstane series

Summary Hydrazones and symmetrical dihydrazones of 2-methyltestosterone and its 17-methyl and 17-ethyl derivatives have been synthesized.Khimiya Prirodnykh Soedinenii, Vol. 2, No. 5, pp. 354–359, 1966     

Derivatives of the sym-octahydroacridine series

4,5-Dihydroxy-, 4, 5-diacetoxy-, 4,5-dichloro-, and 4-hydroxy-5-oxo-sym-octahydroacridines and the N-oxides of 1,2,3,4,7,8-hexahydroacridine and of 4,5-dihydroxy-sym-octahydroacridine have been synthesized. The dehydration of 4,5-dihydroxy-sym-octahydroacridine has led to 1,2, 7,8-tetrahydroacridine. The latter adds two molecules of hydrogen to the double bonds and also one molecule of acetoacetic ester with the formation of, respectively, sym-octahydroacridine and 3-[acetyl(ethoxycarbonyl)methyl]-1,2,3,4,7,8-hexahydroacridine.For part IV, see [12].     

Derivatives in the sym-octahydroacridine series

A number of previously unknown 4, 5-diarylideneoctahydroacridines have been synthesized by the condensation of sym-octahydroacridine with aromatic aldehydes, and their fluorescence has been described.For part III, see [1].     

Synthesis of c-17 trans β-lactams of the androstane series

3,3′-Ethylenedioxyandrost-4-en-17β-ol 1 was converted into the ethyl ester 2 by reaction with potassium metal and ethyl chloroacetate. The ethyl ester 2 on reaction with hydrazine gave the hydrazide 3 . Condensation of 3 with aryl aldehydes gave the Schiff bases 4 . The reaction of Schiff bases 4 with mono-chloroacetyl chloride in the presence of triethylamine afforded the β-lactams 5 .     

Distinction between 17-epimeric hydroxy steroids of the 3,17-dioxygenated androstane series by chemical ionization

The distinction between 17-epimeric 3,17-dioxygenated hydroxyandrostanes has been made by comparison of both their methane or ammonia positive and OH^? negative chemical ionization (CI) mass spectra. In the methane or ammonia positive CI, the 17α-configuration in the eight stereoisomeric 5ξ-androstane-3ξ,17ξ-diols can be determined by the relative abundances of the ion [MH? 2 H₂O]⁺. In the ammonia CI spectra, the ion [M+NH₄? H₂O]⁺ possesses only a low abundance, but a comparison of the relative rates of the loss of water v. the loss of ammonia from [M.NH₄]⁺ in the second field-free region allows a clear distinction to be made between the 17α- and 17β-series. In the OH^? negative CI mass spectra, the 5ξ-androstane-3-one-17ξ-ols produce an intense ion [M? H? H₂O]^? in the 17α-series only.     

Translational energy release and stereochemistry of steroids. 14. Epimeric dihydroxy steroids of the androstane series

The stereochemistry of dihydroxy steroids, both the mode of the A/B ring junctions and the configuration of OH groups, may be determined from translational energy (T50%) measurements for the loss of a CH.3 radical, from the ratios of metastable-ion peak heights to those of the main beam (determined for the dehydration reactions), and by comparing unimolecular and collision-induced, mass-analysed ion kinetic energy spectra of the new main beam of [M-H2O]+ ions (i.e. those formed via dehydration of metastable molecular ions of epimeric hydroxy steroids in the first field-free region of a double-focusing mass spectrometer.     

Synthesis of 14,16-dien-17-yl acetates of androstane series. NMR and mass spectrometry data

On the basis of dehydroepiandrosterone through the Δ¹⁴- and Δ¹⁵-androst-17-ones a series of androsta-14,16-dienyl acetates was obtained, the key compounds in the synthesis of 14-substituted steroids. By the methods of two-dimensional NMR spectroscopy the structure of compounds was proved and a full assignment of signals in the ¹H and ¹³C NMR spectra was performed. With the use of tandem mass spectrometry the main directions of fragmentation of protonated molecules of the synthesized ketones and dienyl acetates were studied.     

Synthesis of derivatives of the androstane series. XXI. Synthesis and properties of some N-acylated androstano[3,2-c]pyrazoles

A method has been developed for synthesizing acylsteroidopyrazoles in which the acyl residues are radicals of natural amino acids. The compounds synthesized possess a high anabolic action and a low toxicity.Khar'kov Scientific-Research Institute of Endocrinology. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 76–81, January–February, 1981.     

Lipase-Catalysed Regioselective Deacetylation of androstane derivatives

A series of acetoxy derivatives of androstane was deacetylated in organic solvents by several lipases. The most satisfactory results were obtained with lipase from Candida cylindracea (CCL) and Candida antarctica (CAL). In some derivatives, CCL and CAL showed an overwhelming regioselectivity towards the removal of the 3β- or the 17β-acetyl group (see Table 2). Three new steroid derivatives were obtained through this approach. A hypothetical rationale for the behaviour of these enzymes is given.     

Gas-liquid chromatographic studies of reactions and structural relationships of steroids. Part III. 11alpha-hydroxysteroids of the androstane and pregnane series.

Qualitative and quantitative effects of classical reactions on steroids observed by gas-liquid chromatography (GLC) under standardized conditions, including the double internal-standard technique, are reported. Simple procedures applicable to nanogram amounts of reactants which afford excellent yields of the major products are described. Reactions studied include the Wolff-Kishner removal of keto groups, their conversion into hydroxyl groups with sodium-ethanol or sodium borohydride and into dioxolone derivatives with ethylene glycol; the conversion of hydroxyl into keto groups with chromium trioxide and to trimethylsilyl (TMS) ethers by hexamethyldisilazane; the hydrolysis of dioxolone and TMS derivatives by H+. Gas-liquid chromatograms of reaction mixtures of single- and multistep reactions readily provide information on the effects on the 11alpha-hydroxy and other functional groups at positions 3 and 17 (androstane series) and positions 3 and 20 (pregnane series), and the retention times of many steroids unavailable from commercial or other sources. GLC data analysis provides relationships between steroid structure and retention time from which methods for the computation of retention times and for steroid identification are designed. The accuracy of the calculation methods is demonstrated.     

1H and 13C NMR spectral assignment of androstane derivatives

(1)H and (13)C NMR spectroscopic data for 5alpha-androstanes and halo-5alpha-androstanes with different substituents at positions C-3, C-9, C-11 and C-17 were examined and assigned by a combination of 1D and 2D NMR experiments. The substituent effects on the (13)C chemical shifts were compared with those of epi-androsterone, used as a reference compound. The coupling constants (n)J((19)F,(13)C) were measured for compounds 6, 8, 11 and 14.     

On the Synthesis of Chloro Derivatives of Five-Membered Heterocyclics via the Lithium Derivatives

In connection with our ¹³C NMR investigations we were interested in obtaining pure samples of 2- and 3-chlorofuran and 2- and 3-chloroselenophene. While direct chlorination with molecular chlorine or other chlorinating agents can successfully be used for the preparation of 2-chlorothiophene,¹ we could not reproduce either yields or isomeric purity in the corresponding chlorination of selenophene.^2,3