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The crystal structures of 3β,19-dihydroxyandrost-5-en-17-one, 5, and its monohydrate, [((5).H 2 O]], are reported. The monohydrate, isolated from a solution of 5 in 50% aqueous methanol, recrystallizes in the orthorhombic space group, P2 1 2 1 2 1 , while that of the anhydrous compound, isolated from solutions of THF, Me 2 CO, EtOAc or dry MeOH, recrystallizes in the monoclinic space group, P2 1 . Apart from the different orientation of the 3-HO group, the conformations of the steroid molecules in 5 and [(5).H 2 O]: are similar. The two-dimensional structure of 5 consists of sheets of molecules formed from strong classical O3-H3⋯O19 (OH) and O19-H19···O3 (OH) , augmented by weaker C-H⋯O hydrogen bonds. Noticeably the presence of the C19 hydroxyl group results in the replacement of the O3-H3⋯O17 (one) hydrogen bonds as the strongest intermolecular interaction found in the stable polymorphs of the mono-hydroxylated compound, 3β-hydroxyandrost-5-en-17-one (dehydroepiandrosterone). An additional structural difference between 3β-hydroxyandrost-5-en-17-one and 3β,19-dihydroxyandrost-5-en-17-one is that the steroid molecules are most strongly linked head-to-tail in the former but head-to-middle fashion in the latter. In the three dimensional structure of [((5).H 2 O]], each steroid molecule is directly connected to another by a O19-H19⋯O3 (OH) hydrogen bond and indirectly to two others via the water molecule. Each water molecule forms three hydrogen bonds, namely O3-H3⋯Ow, Ow-Hw1⋯O17 and Ow-Hw2⋯O19. As found for most hydrated steroids, the hydrate molecules have strong influences on the structure. In addition to the reporting of the crystal structures of 5 and [(5).H 2 O], we report on a survey of the crystal structures of related di- and tri- hydroxy-17-one derivatives as well as solvated compounds., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The crystal structures, Hirshfeld surface analyses and electrostatic potential surfaces of the di- and tri-hydrates of (5α,17E)-17-hydrazonoandrostan-3-ol, 3, namely [3·(H 2 O) 2 ] and [3·(H 2 O) 3 ], are reported. The trihydrate, isolated from a solution of 3 in moist methanol, recrystallizes in the orthorhombic space group, P2 1 2 1 2 1 , while that of the dihydrate, isolated from a 1:1 aqueous methanol solution, recrystallizes in the monoclinic space group, P2 1 . The asymmetric unit of the trihydrate involves one steroid and three water molecules, while that of the dihydrate has two similar but independent steroid molecules and four hydrate molecules. Very similar conformations are found for the steroid molecules in both hydrates. As expected, the different mole ratios of water: steroid have major influences on the structures. In both cases, complex crystal structures are constructed from various classical hydrogen bonds, involving the hydrate molecules and the hydroxy and hydrazonyl moieties of the steroid. In the trihydrate, there are no direct connections between the steroid molecules, instead the water molecules link the steroid molecules, with only weak van der Waals forces between the steroid molecules. There are some direct links between the steroid molecules in the dihydrate, involving OH(steroid hydroxyl)⋯O(steroid oxo) hydrogen bonds, in a head to head fashion, and OH⋯N(hydrazonyl) hydrogen bonds, in a head to tail fashion. However, the major occurrence throughout the structure is of steroid molecules linked by water molecules., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Drostanolone is one of the most frequently detected anabolic androgenic steroids in doping control analysis. Here, we studied drostanolone urinary metabolic profiles using liquid chromatography quadruple time of flight mass spectrometry (LC-QTOF-MS) in full scan and targeted MS/MS modes with accurate mass measurement. The drug was administered to one healthy male volunteer and liquid-liquid extraction along with direct-injection were used to analyze urine samples. Chromatographic peaks for potential metabolites were identified with the theoretical [M-H](-) as a target ion in a full scan experiment and actual deprotonated ions were analyzed in targeted MS/MS mode. Eleven metabolites including five new sulfates, five glucuronide conjugates, and one free metabolite were confirmed for drostanolone. Due to the absence of useful fragment ions to illustrate the steroid ring structure of drostanolone phase II metabolites, gas chromatography mass spectrometry (GC-MS) was used to obtain structural details of the trimethylsilylated phase I metabolite released after enzymatic hydrolysis and a potential structure was proposed using a combined MS approach. Metabolite detection times were recorded and S4 (2α-methyl-5α-androstan-17-one-6β-ol-3α-sulfate) and G1 (2α-methyl-5α-androstan-17-one-3α-glucuronide) were thought to be new potential biomarkers for drostanolone misuse which can be detected up to 24days by liquid-liquid extraction and 7days by direct-injection analysis after intramuscular injection. S4 and G1 were also detected in two drostanolone-positive routine urine samples., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The preparation of novel steroidal heterocycles containing the 7-aryl-substituted 1,2,4-triazolo[1,5-a]pyrimidine moiety fused to the 16,17-positions of the steroid nucleus is described. The Aldol reaction of 4-aza-androst-3,17-dione (1a) and dehydroepiandrosterone (DHEA, 1b) with aromatic aldehydes was catalyzed by KF/Al(2)O(3) to give the corresponding 3-oxo-4-aza-5α- and 3β-hydroxy-5-en-16-arylidene-17-ketosteroids (2a-r). Subsequently, the intermediates 2a-r reacted with dinucleophilic 3-amino-1,2,4-triazole in presence of t-BuOK to afford the title compounds (3a-r). All the synthesized heterosteroids are new and are currently being evaluated for their biological activities., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Methyldrostanolone (2alpha,17alpha-dimethyl-17beta-hydroxy-5alpha-androstan-3-one) was synthesized from drostanolone (17beta-hydroxy-2alpha-methyl-5alpha-androstan-3-one) and identified in commercial products. Cultures of cryopreserved human hepatocytes were used to study the biotransformation of drostanolone and its 17-methylated derivative. For both steroids, the common 3alpha- (major) and 3beta-reduced metabolites were identified by GC-MS analysis of the extracted culture medium and the stereochemistry confirmed by incubation with 3alpha-hydroxysteroid dehydrogenase. Structures corresponding to hydroxylated metabolites in C-12 (minor) and C-16 were proposed for other metabolites based upon the evaluation of the mass spectra of the pertrimethylsilyl (TMS-d(0) and TMS-d(9)) derivatives. Finally, on the basis of the GC-MS and (1)H NMR data and through chemical synthesis of the 17-methylated model compounds, structures could be proposed for metabolites hydroxylated in C-2. All the metabolites extracted from hepatocyte culture medium were present although in different relative amounts in urines collected following the administration to a human volunteer, therefore confirming the suitability of the cryopreserved hepatocytes to generate characteristic metabolites and study biotransformation of new steroids.

The ability of a genus of cephalosporium-like fungus isolated from soil, Acremonium strictum PTCC 5282, for hydrocortisone biotransformation has been investigated. This potential had not been previously examined. The fermentation yielded 11beta,17beta-dihydroxyandrost-4-en-3-one, 11beta,17alpha,20beta,21-tetrahydroxypregn-4-en-3-one and 21-acetoxy-11beta,17alpha,20-trihydroxypregn-4-en-3-one. Each microbial metabolite was purified and characterized using spectroscopic methods.

A new convergent synthesis of the antitumor steroid formestane (4-OHA) 5 has been performed from the easily available epimeric mixture of 5 alpha- and 5 beta-androst-3-en-17-one 1a and 1b in order to attempt a yield improvement. A two-step oxidative route followed by base-catalyzed isomerization was applied to the 5 alpha- and 5 beta-epimers 1a and 1b, either as a mixture or separately, leading to the title compound 5. From epimer 1a an efficient process was attained to prepare the desired aromatase inhibitor formestane. Epimer 1b led to the formation of the same compound 5. Additionally, 1b have also been converted in 5 beta-hydroxyandrostane-3,17-dione 12 and androst-4-ene-3,17-dione 13, revealing an unexpected reactivity of the 3 beta,4 beta-epoxy-5 beta-androstan-17-one intermediate 6 formed from 1b during the first oxidative step with performic acid. Cleavage of the epoxide 6 led to the trans-diaxial and the trans-diequatorial vic-diols 7 and 8 and to the 1,3-diol 9. The formation of the abnormal products 8 and 9 were investigated through X-ray and deuterium labeling studies. Diol 8 was formed through a trans-diequatorial epoxide ring opening and the 1,3-diol 9 was formed through an intramolecular rearrangement involving a 1,2-hydride shift. All the vic-diols 3, 7 and 8 formed, proved to be good precursors for the synthesis of the target compound 5.

16alpha-Hydroxymethyl-5alpha-androstane-3beta,17beta-diol and 16beta-hydroxymethyl-5alpha-androstane-3beta,17beta-diol, were obtained from reduction of 16-acetoxymethylene-5alpha-androstan-17-one. The corresponding 16alpha,17alpha- and 16beta,17alpha-hydroxymethyl isomers were obtained by neighboring group participation of the 16- and 17-acetates, respectively. The reactions involving carbocation formation also led to ring D rearrangement products.

The synthesis and biological evaluation of 4-thiosubstituted derivatives of 1,4-androstadienedione, 4,6-androstadienedione, and 1,4,6-androstatrienedione as inhibitors of aromatase are described. Inhibitory activity of synthesized compounds was assessed using a human placental microsomal preparation as the enzyme source and [1 beta-3H]androstenedione as substrate. Under initial velocity assay conditions of low product formation, the inhibitors demonstrated potent inhibition of aromatase, with apparent Kis ranging from 9.8 to 137 nM and with Km for androstenedione being 38 nM. However, unlike other 1,4-androstadienediones and 1,4,6-androstatrienediones in which time-dependent inactivation was observed, the 4-thiosubstituted analogs were found to be competitive inhibitors and did not produce any time-dependent inactivation of aromatase.

The molecular structure of 3,3-difluoro-5 alpha-androstane-17 beta-ol acetate was analyzed by 1H, 13C, and 19F nuclear magnetic resonance (NMR) techniques; two-dimensional NMR was used to assigned 1H and 13C resonances. The 1H NMR spectrum in deuterated chloroform shows three sharp singlets (delta = 0.74, 0.79, and 2.00 ppm) integrating for three protons each, an isolated triplet at 4.55 ppm integrating for one proton, and overlapping multiplets between 0.72 and 2.12 ppm integrating for 31 protons. The 13C spectrum shows 18 resonances between 10 and 55 ppm, and three additional resonances at 82.9, 124.0, and 171.5 ppm. The 19F[1H] spectrum shows two sets of doublets (observed 2J = 150 Hz) at 5.00 and -4.80 ppm. Multiplets arising from 19F-13C J-coupling provide the starting assignment for all resonances by means of 1H homonuclear correlation (COSY) and 1H-13C heteronuclear correlation spectroscopy.

Carbon-13 nuclear magnetic resonance spectra for 31 3 beta-hydroxy and acetoxy androstane derivatives bearing vicinal oxygenated functions at ring D with and without oxygenated functions at C-6 are reported. Relative substituent effects are discussed.