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.     

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.     

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.     

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.     

Über die Darstellung von 3β, 16α-und 3β, 16β-Diacetoxy-5α-pregnan-20-on

Zusammenfassung Die Synthese von 3, 16-Diacetoxy-5 -pregnan-20-on (VI) aus 3-Acetoxy-5 -pregn-16-en-20-on und eine verbesserte Darstellung von 3, 16-Diacetoxy-5 -pregnan-20-on (III) aus 3-Acetoxy-pregna-5, 16-dien-20-on werden beschrieben.     

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.     

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…     

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.     

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.     

Crystal Structure of 6β,7β,14β-Trihydroxy-1α-acetoxy-7α,20-epoxy-ent-kaur-16-en-15-one

6β,7β,14β-Trihydroxy-1α-acetoxy-7α,20-epoxy-ent-kaur-16-en-15-one was isolated from the natural plant of Isodon japonica (Burm.f), Haravar. galaucocalyx (maxim) Hara. The structure was elucidated by means of spectral and chemical studies. In addition, its crystal was determined by single-crystal X-ray diffraction analysis. It crystallizes in triclinic, space group P1, Z = 2, a = 6.3506(4), b = 13.5766(8), c = 15.2777(9) , α = 80.506(1), β = 83.856(1), γ = 88.307(1)o, C25H36O9, Mr = 480.54, V = 1291.64(13) 3, Z = 2, Dc = 1.236 g/cm3, F(000) = 516, μ = 0.093 mm-1, S = 0.988, the final R = 0.0761 and wR = 0.1955. Flack factor is 0.02(19), and the largest peak and deepest hole on the final difference Fourier map are 0.556 and –0.265 e/3, respectively. The X-ray diffraction shows the existence of intermolecular C–H…O (DA) hydrogen bonds between adjacent molecules.     

Ab Initio Study of Prednisolone, 6α-Fluoroprednisolone, 9α-Fluoroprednisolone,and 6α,9α-Difluoroprednisolone

A theoretical study of prednisolone, 6-fluoroprednisolone, 9-fluoroprednisolone, and 6,9-difluoroprednisolone has been performed at the ab initio HF/6-31G, MP2/6-31G, and B3LYP/6-31G levels. Structural information and the electronic features of prednisolone and its derivatives and the synergistic effect of 6,9-difluoroprednisolone was examined. Contrary to the AM1 and MNDO results, we found 9-fluoroprednisolone is more stable than the 6-fluoroprednisolone. The increased corticosteroid activity of the 6,9-difluoroprednisolone is most likely due to electronic effects, mainly related to the receptor binding.     

Bismuth(III) triflate-catalyzed rearrangement of 16α,17α-epoxy-20-oxosteroids. Synthesis and structural elucidation of new 16α-substituted 17α-alkyl-17β-methyl-Δ-18-norsteroids

The use of bismuth(III) triflate for the rearrangement of 16α,17α-epoxy-20-oxosteroids is reported. The reactions occur under truly catalytic conditions to afford novel 17α-alkyl-17β-methyl-Δ¹³-18-nor products bearing different O-containing substituents at C16. When the reaction is performed in the absence of acylation agent a mixture of isomeric 16α- and 16β-hydroxy derivatives is obtained, whereas when carried out in the presence of such reagents, the reaction selectively affords the corresponding 16α-acyl rearranged products. The chemoselective rearrangement of 5β,6β;16α,17α-diepoxy-20-oxopregnan-3β-yl acetate to afford a ‘backbone’ rearranged product bearing the 16α,17α-epoxide group is also reported. Some mechanistic considerations are provided. All rearranged products were the subject of comprehensive structural elucidation, by the use of X-ray crystallography and 2D NMR.     

Synthesis of symmetrical acetylenic hydrocarbons and their α,ω-di-derivatives from α,α,α-trichloro- and α,α,α,ω-tetrachloro-alkanes

Summary By the action of sodium in xylene on polychloro hydrocarbons containing -CCl₂-CCl₂- or- CC1=CC1-, groupings the corresponding symmetrical acetylenic hydrocarbons containing 10,14, and 18 carbon atoms in the molecule were obtained. From ,-disubstituted tetrachloroalkanes by the same method 1,10-diethoxy-5-decyne, 1,14-diethoxy-7-tetradecyne, and 1,14-bisdiethylamino-7-tetradecyne were obtained.The spectra were determined in the Optical Laboratory of the Institute of Heteroorganic Compounds of the USSR by N. A. Chumaevskii, who we thank.     

Conformation of α,α,α′-Trisubstituted Cyclododecanone

Ten α,α,α′-trisubstituted cyclododecanones were synthesized and characterized by elemental analyses, infrared, 1^H NMR and 13^C NMR spectra, and X-ray diffraction. NMR data could not give conformational information clearly, but some of their ring skeleton conformations of cyclododecanone moiety were showed to remain the unchanged [3333]-2-one conformation with little distortion, while the others were changed to the [3324]-2-one conformation in their crystal structures. These are consistent with the results of molecular mechanics calculation with Sybyl 6.9 software and Tripos force field, and semi-empirical quantum calculation with AM 1 method in Gaussian 98 software. Two geminal substituting groups are located at α-corner carbon atom, and the third group is at α-side-exo carbon atom in both conformations. Both [3333]-2-one and [3324]-2-one conformations are present in a dynamic equilibrium in the solution, but only one preferred conformation exists in the crystal solid.     

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...     

Automatic assembly of skeleton structures. 3. Stereoselective synthesis,stereochemistry, and cyclization ofd,l-α,α'-dioxy-α,α'-di-tert-butylglutaric acid

Stereoselective synthesis of d,l-,-dioxy-,-di-tert-butylglutaric acid hydroxyiminolactonitrile (3) was conducted by the reaction of dipivaloylmethane with HCN in ether. The corresponding hydroxylacetonitrile (4) and amide (5), acid (6), and its ester (7), from which dilactone (8) was synthesized with preparative yields, were obtained from3. Benzyl amide (9) was obtained by the reaction of8 with BnNH₂. The iminolactone structure3 of dipivaloylmethane bis-cyanohyrin, thecis-pseudo-a orientation of the functional substituents in3–7 and9, and the structure of the dilactone8 were confirmed by the¹H,¹³C NMR,IR and mass spectra.For previous communication, see [2].N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 117977 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 7, pp. 1591–1601, July, 1992.