Ionic liquid-promoted Wagner-Meerwein rearrangement of 16α,17α-epoxyandrostanes and 16α,17α-epoxyestranes

Ionic liquids 1-butyl-3-methylimidazolium hexafluorophosphate ([bmim](+)[PF(6)](-)) and 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim](+)[BF(4)](-)) were found to promote an unusual Wagner-Meerwein rearrangement of steroidal 16α,17α-epoxides leading to unnatural 13-epi-18-nor-16-one derivatives as the main products. These compounds were isolated in good to excellent yields. 16α-Hydroxy-Δ(13)-18-norsteroids, the results of the usual rearrangement, were obtained as minor components of the reaction mixtures. The ionic liquid [bmim](+)[PF(6)](-) was shown to induce C-ring aromatization of 16α,17α-epoxyestranes due to the formation of HF, the hydrolysis product of [PF(6)](-). Increasing amounts of HF and [PO(2)F(2)](-) were detected by (19)F and (31)P NMR when the ionic liquid was reused. The structures of the steroidal products, 16-oxo-18-nor-13α-steroid derivatives, 16α-hydroxy-Δ(13)-18-norsteroids, and C-aromatic compounds were determined by two-dimensional NMR techniques and high-resolution mass spectrometry (HRMS). The ionic liquids were recirculated efficiently.     

Wagner-Meerwein rearrangement of steviol 16α,17- and 15α,16-epoxides

16α,17- and 15α,16-Epoxy derivatives of diterpenoid steviol having ent-kaurane structure were found for the first time to undergo Wagner-Meerwein rearrangement in alkaline medium or by the action of boron trifluoride-diethyl ether complex to give products with ent-beyerane structure. The geometric parameters of steviol 16α,17- and 15α,16-epoxides were determined by X-ray analysis.     

Density and viscosity of 16α,17α-epoxyprogesterone solutions in chloroform

density and viscosity of 16α,17α-epoxyprogesterone solutions in chloroform were determined over the concentration range up to ∼1.9 mol l⁻¹ at temperatures from 287.65 to 321.15 K. The relative viscosity data were correlated using the extended Jones-Dole equation, a good accuracy of the correlation being obtained.     

Transformed steroids. 185. Use of the Nicholas reaction for regio- and stereo-selective transformation of 16α,17a-epoxy-17Β-ethynyl-androstanes into 16α,17α-cis-disubstituted steroids

The HBF₄·Et₂O-catalyzed methanolysis reactions of the 16, 17-oxides of 17-ethy-nylandrost-4-en-3-one and its dicobalt hexacarbonyl complex were studied. It was shown that these reactions proceed with the same regiodirectivity of the oxide ring opening at the tertiary center but with a different mode of stabilization of the intermediates formed. The reaction of the free oxide proceeds without the inclusion of the external nucleophile and is concluded by the Wagner-Meerwein rearrangement; the C¹⁷-carbocation formed in the Co-coordinated oxide is stabilized by the addition of the methoxide ion and the elimination of a proton or of water. The opening of the oxide ring of dicobalt tetracarbonyl 16, 17-epoxy-17-ethynylandrost-4-en-3-one can be realized with decomplexation accompanied by carbonylation and heterocyclization.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp.1180–1184, May, 1991.     

Practical synthesis of 16α-bromo-17α-hydroxysteroids via a Raney Ni-catalyzed bromide exchange reaction

D-ring modified glucocorticoids are attractive synthetic targets owing to their broad application in medicinal chemistry. Herein, we reported a practical synthesis of 16α-bromo-17α-hydroxysteroids from easily available 16β-bromo isomers via a Raney Ni-catalyzed bromide exchange reaction. The catalytic Finkelstein-type reaction features high yield, mild reaction condition, short reaction time and simple operation. The method provided an efficient approach to prepare 17α-hydroxy-15-pregnen-20-ones.     

Regioselective Decomposition of 11-Substituted-16α,17α- methyleneazopregna-1,4-dien-3,20-dione

16α, 17α-Methylenepregnanes are not only the important chemical intermediates but also the excellent pharmaceutical candidates1. In order to study the structural relationship of D-ring of corticosteroid to the antiinflammative activity, 11-substituted-1…     

Reaction of 5β,6β-epoxy-16α,17α-cyclohexapregnane with methylmagnesium iodide

On treatment with methylmagnesium iodide, 3β-acetoxy-5β,6β-epoxy-16α,17α-cyclo-hexapregnan-20-one undergoes 3-O-deacetylation along with the opening of the 5β,6β-epoxide ring to form 5α-methyl-6β-hydroxy steroid and the 6α-methyl-6β-hydroxy isomer, the 20-keto group remaining intact.     

Synthesis of 4-hetero-16α,17α-cyclohexanopregnanes and evaluation of their cytotoxicity against the HeLa cell line

Russian Chemical Bulletin - The oxidation of the ring A of 16α,17α-cyclohexanoprogesterone gave 5-oxo-A-nor-3,5-secopregnan-3-oic acid. The subsequent ring A closure in the latter...     

Autooxidation of Δ17(20)-20-hydroxy derivatives of steroids. Synthesis of 3β-acetoxy-17α-hydroperoxy-16α-methylpregn-5-en-20-one and its reduction to 17α-hydroxy derivative

An efficient procedure was proposed for the synthesis of 3β-acetoxy-17α-hydroperoxy-16α-methylpregn-5-en-20-one. Optimal conditions were found for the combined process including 1,4-addition of methylmagnesium bromide at the Δ¹⁶-20-oxo fragment of dehydropregnenolone acetate and autooxidation of resulting bromomagnesium 3β-acetoxy-16α-methylpregna-5,17(20)-dien-20-olate. The subsequent reduction of the 17α-hydroperoxy group and hydrolysis of the 3β-acetoxy group afforded 17α-hydroxy-16α-methyl-substituted dehydropregnenolone acetate and its 3-hydroxy analog in high yield.     

Synthesis and Transformations of 20-Isoxazolylsteroids with Modified D Ring: I. Synthesis of 16α,17α-Epoxyderivatives

Synthesis of 16,17-epoxy-20-isoxazolylsteroids was carried out starting with dehydropregnenolone acetate. Transformation procedures for preparation therefrom of open-chain compounds were considered. Physico-chemical characteristics of compounds synthesized were investigated.     

The structure of 16, 17β-epoxy-17α-pregn-5-en-3β-ol-20-one monohydrate

The structure of the title compound (1) has been studied by means of X-ray diffraction. The region of cycleD in epoxide1 was compared with that of the 16,17-epoxy derivatives of progesterone and pregnenolone (studied previously) as well as with that of the respective 16,17- and 16,17-cyclopropano analogs. In contrast to the 16,17-epoxy-20-oxo derivatives, in compound1 the electron conjugation of the epoxide ring with the CH₃CO group at C(17) is partly disrupted. Moreover, the steric congestion at C(17) is significantly less pronounced in 16,17-epoxide1 than in its 16,17-counterpart. Both of these factors, especially steric decongestion, are favorable for nucleophilic attack at C(17) in the molecule of1. The X-ray diffraction data do not contradict the previously advanced mechanism of epoxide ring opening in 16,17- and 16,17-epoxy-20-oxo steroids by nucleophilic reagents.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 401–405, February, 1993.     

Transformation of 5α-H-pregn-16-en-3β-ol-20-one into pregn-4-ene-9α,16α,17α-triol-3,20-dione 16,17-acetonide

A preparative method was proposed for the preparation of pregn-4-ene-9,16,17-triol-3,20-dione 16,17-acetonide (2) from 5-H-pregn-16-en-3-ol-20-one (1). The key stage in the proposed sequence of the reactions is the microbiological 9-hydroxylation and introduction of the 4-en-3-one grouping into the molecule of1 by R- and S-dissociative forms of the Rhodococcus sp. strain.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 8, pp. 1898–1901, August, 1992.     

Synthesis and transformations of the 20-substituted derivatives of 16α,17α-epoxy-5α-pregnane-3Β,21-diol-20-ones

A new and more effective sequence of reactions is proposed for the production of 16,17-isopropylidenedioxy-5-pregnane-3,21-diol-20-one. It uses methods previously unused for 5-H-steroids and involves 21-hydroxylation of 16,17-epoxy-5-pregnan-3-ol-20-one with diacetoxyiodobenzene and cis-opening of the obtained 21-hydroxy-16,17-epoxy-5-pregnane-3,21-diol-20-one by acetic acid in the presence of epoxycarbonylhydrazine, followed by condensation of the obtained product with acetone.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1185–1188, May, 1991.     

Synthesis of 5α, 13α, 14α-Androstan-16-One and 5α, 13β, 14β—Androstan-16-One Using a Novel 17–16 Carbonyl Transposition

In the course of current work on the conformational analysis of cis-hydrindanones¹, we required 5α, 13α, 14α and 5α, 13β, 14β-androstan-16-one 5 and 10 the C and D rings of which provide rigid models of the two conformations of cis-hydrindan-2-one.     

Characterization of 17α-hydroxysteroid dehydrogenase activity (17α-HSD) and its involvement in the biosynthesis of epitestosterone

Background  

Epi-testosterone (epiT) is the 17α-epimer of testosterone. It has been found at similar level as testosterone in human biological fluids. This steroid has thus been used as a natural internal standard for assessing testosterone abuse in sports. EpiT has been also shown to accumulate in mammary cyst fluid and in human prostate. It was found to possess antiandrogenic activity as well as neuroprotective effects. So far, the exact pathway leading to the formation of epiT has not been elucidated.     

Conversion of Epiandrosterone Into 17β-Amino-5α-androstane

A new method for synthesizing 17-amino-5-androstane was developed based on tigogenin. The configuration at C-17 was proved by PMR.     

Key structures for the synthesis of steroid antitumor agents. Synthesis of 16-dehydro-17-carbaldehydes of 13β- and 13α-estratriene series

Russian Chemical Bulletin - A convenient preparative synthesis of 3-methoxyestra-1,3,5(10),16-tetraene-17-carb-aldehyde and its epimeric 13α-analog, the key structures in the synthesis of...     

Transformed steroids. 189. Synthesis and transformations of 21-hydroxy-5α-H-pregnane 2′,2′-dimethyl-[16α,17α-d]-thioxalanes

In a continuation of the research on use of 20-keto-16,17-epoxysteroid 20-hydrazones for synthesis of 17-thio analogs of 20-ketosteroid 16,17-acetonides [2, 3], we synthesized 5-H-pregnane-3,16,21-trihydroxy-17-thiol-20-one 16,17-acetonide and found methods for its microbiological dehydrogenation and hydroxylation into ⁴-3-keto-and 9-hydroxy-⁴-3-keto derivatives.See [1] for Communication 188.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 5, pp. 1182–1186, May, 1992.