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 of the 11β-hydroxymethyl-androst-4-en-3,17-dione

The 11β-hydroxymethyl-androst-4-en-3,17-dione 5 was prepared within five synthetic steps starting from the commercially available adrenosterone with an overall yield of 24%. The 11-ketosteroid 1 was subjected to a Peterson methylenation. The subsequent hydroboration/oxidation sequence in position 11 was regio- and stereoselectively conducted using the borane-methyl sulfide complex at 0 °C. The target molecule was then obtained by deprotection using in situ generated TMSI.     

Simple Synthesis of 17α,20β-Dihydroxypregn-4-en-3-one

Reduction of 17-hydroxyprogesterone (1) with NaBH ₄ produces 17,20-dihydroxypregn-4-en-3-one (2) and pregn-4-en-3,17,20-triol (3)     

Synthesis of 19-hydroxypregn-4-en-20-one and 19-hydroxy-5β-pregn-3-en-20-one that selectively bind to membrane progesterone receptors,and assessment of their immunomodulatory effects

Russian Chemical Bulletin - A new approach to the synthesis of isomeric 19-hydroxypregn-4-en-20-one (1) and 19-hydroxy-5β-pregn-3-en-20-one (2), the selective ligands of membrane progesterone...     

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.     

Synthesis of nitrogen-containing derivatives of 17(20)-pregnenoic, 17β-hydroxypregnanoic,and 17α-hydroxypregnanoic acids as new potential antiandrogens

A general scheme for the synthesis of oxazoline and benzoxazole derivatives of [17(20)E]-21-norpregnene differing in the structure of the steroid moiety as well as amides of 17β-hydroxy-3-oxopregn-4-en-21-oic and 17α-hydroxy-3-oxopregn-4-en-21-oic acids was developed. The scheme involved synthesis of the steroid building blocks (appropriately protected derivatives of pregn-17(20)-en-21-oic, 17β-hydroxypregnan-21-oic, and 17α-hydroxypregnan-21-oic acids) and subsequent transformation of these building blocks into the target compounds. Following the developed scheme, synthesis of new nitrogen-containing steroid derivatives exhibiting antiandrogenic activity was enabled.     

Selective synthesis of the two main progesterone metabolites, 3α-hydroxy-5α-pregnanolone (allopregnanolone) and 3α-hydroxypregn-4-en-20-one,and an assessment of their effect on proliferation of hormone-dependent human breast cancer cells

Russian Chemical Bulletin - A directed synthesis of two progesterone metabolites, allopregnanolone and 3a-hydroxy-pregn-4-en-20-one, from Δ16-pregnanolone and progesterone, respectively, was...     

Transformed steroids. 190. Influence of Co-complexation on the epoxide ring opening of 17β-ethynyl-16α,17α-epoxyandrost-4-en-3-one on reacting with pyridine hydrofluoride,pyridine hydrochloride,and pyridine thiocyanate

The epoxide ring opening of 16,17-epoxy-17-ethynylandrost-4-en-3-one and its dicobalt hexacarbonyl complex on reacting with Py·HF, Py·HCl, and Py·HSCN was studied. The results of these reactions and the structure of the end products depend not only on the complexation of the acetylene bond, but also on the nucleophilic reagent used. On the basis of the reaction of a Co-coordinated 16,17-epoxy-17-ethynylandrost-4-en-3-one there has been developed a preparative method for the synthesis of pregn-4-ene-3,20-dione-[17,16-d]-1,3-oxazolidin-2-one.N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117913 Moscow. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 11, pp. 2661–2666, November, 1992.     

Mass spectrometric characterization of isomeric terpenoic acids from the oxidation of α-pinene, β-pinene, d-limonene, and Δ3-carene in fine forest aerosol

In this study, we present liquid chromatographic and mass spectral data for predominant terpenoic acids formed through oxidation of α-pinene, β-pinene, d-limonene, and Δ(3)-carene that occur in fine forest aerosol from K-puszta, Hungary, a rural site with coniferous vegetation. Characterization of these secondary organic aerosol tracers in fine ambient aerosol is important because it allows one to gain information on monoterpene precursors and source processes such as oxidation and aging processes. The mass spectral data were obtained using electrospray ionization in the negative ion mode, accurate mass measurements, and linear ion trap tandem mass spectrometric experiments. Emphasis is given to the mass spectrometric differentiation of isobaric terpenoic acids, such as, e.g. the molecular weight (MW) 186 terpenoic acids, cis-pinic, cis-caric, homoterpenylic, ketolimononic, and limonic acids. Other targeted isobaric terpenoic acids are the MW 184 terpenoic acids, cis-pinonic and cis-caronic acids, and the MW 204 tricarboxylic acids, 3-methyl-1,2,3-butanetricarboxylic and 3-carboxyheptanedioic acids. Fragmentation pathways are proposed to provide a rational explanation for the observed isomeric differences and/or to support the suggested tentative structures. For the completeness of the data set, data obtained for recently reported lactone-containing terpenoic acids (i.e. terpenylic and terebic acids), related or isobaric compounds (i.e. norpinic acid, diaterpenylic acid acetate, and unknown MW 188 compounds) are also included, the rationale being that other groups working on this topic could use this data compilation as a reference.     

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 Hydroxylated Sterols(Ⅱ)--Synthesis of 24-Methylenecholest-4-en-3β,6α-diol

In our study on the soft coral,Alcyonium patagonicum,a new hydroxylated sterol,24-methylenecholest-4-en-3β,6α-diol(1) exhibiting a potent activity to murine leukemia cells(IC50=1 μg/mL) has been isolated[1] and synthesized[2,3].As a part of our studies on the relationship between the chemical structure and the biological activity of the hydroxylated sterols,the synthesis of 24-methylenecholest-4-en-3β,6α-diol(2) is reported here.     

Study on the tetracyclic diterpenoids 4.The solvolysis of methyl 14-β-mesyloxy-ent-kaur-15-en-19-oate

Grandiflorenic acid(1),possessing potent contragestational activity,is an ent-kauranediterpenoid.It has been isolated from Mexical medicinal plant zoapatle(Montanoa tomento)In connection with our synthetic work on ent-kaurane diterpenoids,we are interested in theconversion of stevioside(2)occurred abundantly in Stevia rebaudiana into grandiflorenic acid     

Functionalization of alkanes and cycloalkanes by superelectrophiles. 15. Carbonylation of cycloheptane,cyclooctane, and isomeric monoalkylcyclohexanes with CO in the presence of CBr4·2AlBr3 to form individual esters of tertiary carboxylic acids of the cyclohexane series

Cycloheptane, methylcyclohexane, cyclooctane, and ethylcyclohexane were selectively carbonylated with CO. The reactions of cycloalkanes with CO at –40 °C in the presence of the superelectrophilic system CBr₄·2AlBr₃ in CH₂Br₂ followed by treatment of the reaction mixtures with alcohols afforded esters of 1-methylcyclohexanecarboxylic acid (in the reactions of cycloheptane and methylcyclohexane) or esters of 1-ethylcyclohexanecarboxylic acid (in the reactions of cyclooctane and ethylcyclohexane) in 70—80% yields with respect to CBr₄·2AlBr₃. The reaction of 1,3-dimethylcyclohexane at –40 °C and the reactions of cyclooctane and ethylcyclohexane and at –20 °C proceeded nonselectively to form four isomeric esters C₈H₁₅COOR.     

A versatile and straightforward approach to the 21-oxidation of β-substituted and α,β-unsaturated 20-oxosteroids

21-Hydroxylation and acetoxylation of 20-oxosteroids, either α,β-unsaturated or β-substituted, were successfully achieved through oxidation of the corresponding silyl enol ethers withm-CPBA followed by smooth hydrolytic cleavage of the 21-alkylsilyloxy derivatives. These conditions, which have not been previously used to synthesize such compounds, allow a high degree of regio and chemoselectivity and are specially useful for the chemical synthesis of 16α,21-dihydroxy-20-oxosteroids.     

Synthesis of (E)-prop-1-ene-1,3-diyldibenzene derivatives via direct decarboxylative coupling of α,β-unsaturated carboxylic acids with benzyl boronic acid pinacol ester

The first copper-catalyzed cross-coupling reaction between benzyl boronic acid pinacol ester and α,β-unsaturated carboxylic acids was described. The ready availability of the starting materials and excellent E selectivity make this protocol a safe and operationally convenient strategy for the efficient synthesis of (E)-prop-1-ene-1,3-diyldibenzene derivatives.     

IBX in an ionic liquid: eco-friendly oxidation of 17α-methylandrostan-3β,17β-diol, an intermediate in the synthesis of anabolic oxandrolone

An easily available hypervalent iodine(V) reagent, 2-iodoxybenzoic acid (IBX) immobilized in the ionic liquid [bmim][Br] was found to be an efficient and eco-friendly protocol for the oxidation of 17α-methylandrostan-3β,17β-diol (1). At ambient temperature oxidation of 1 with IBX gave mestanolone (2) in good yield and with an increased stoichiometric amount of IBX, oxidation adjacent to the carbonyl functionality (α,β-unsaturation) occurred to give dehydrogenated 17β-hydroxy-17α-methyl-Δ¹-androsten-3-one (3) as the major product in a one-pot reaction. The product is easily obtained by extraction with diethyl ether and evaporation of the solvent.     

New variants in the total synthesis of 14β-hydroxy-17α,R-8α,9β-estradiol derivatives

Two procedures were developed for the synthesis of 17-alkyl-8,9-estra-1,3,5(10)-triene-3,14,17-triols from 3-methoxy-estra-1,3,5(10),8(9),14(15)-pentaene-17-one (1) using photosensitized oxidation by atmospheric oxygen or ionic hydrogenation in the presence of oxygen. It was shown that 17-hexynyl-8,9-estra-1,3,5(10)-triene-3,14,17-triol (23) and its 3-methoxy derivative (26) inhibit K⁺,Na⁺-ATPase, with inhibition degree increasing on introduction of an oxygen-containing substituent into position 17. For the first time steroids were found with ₂-adrenoblocking action.Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 1, pp. 207–212, January, 1993.     

Molecular motions and the structure ofβ-cyclodextrin inclusion complexes with ferrocene, [3]-ferrocenophane-1,3-dione and ruthenocene

Spin-lattice relaxation time measurements in laboratory and rotating frames as well as proton second moment analysis have been used to investigate molecular motions in -cyclodextrin (CD) and its solid inclusion complexes with the title organometallic compounds. Different dynamical processes have been identified in the host lattice along with high mobility of the ferrocene and ruthenocene guest molecules. The Arrhenius parameters of all motions were obtained. The assumption based on the second moment measurements was made about the axial structure of the ferrocene complex and the equatorial one of the ruthenocene complex at low temperatures. The bridged ferrocenophane molecule was shown to be rigid on the NMR time scale. The ternary inclusion complex of -CD with ruthenocene and iodine was also studied and no evidence of redox reactions was observed.     

Synthesis and Crystal Structure of a Novel 14,20-Annulated Pentacyclic Steroid 17(S)-Methyl-13β-hydroxyl-14(R),20(S)-epoxy-pregn-4-en-3-one

The title compound 17(S)-methyl-13β-hydroxyl-14(R),20(S)-epoxy-pregn-4-en-3-one was synthesized by an improved tandem reaction, and its structure was determined by IR, NMR, HR MS and X-ray single-crystal diffraction. The crystal belongs to orthorhombic, space group P212121 with a = 10.55248(15), b = 12.14700(16), c = 14.56841(18) ?, V = 1867.39(4) ?3, Z = 4, Dc= 1.175 g/cm3, μ= 0.604 mm-1, F(000) = 720, the final R = 0.0400 and w R = 0.1072 for 3610 observed reflections with I 2σ(I).