17a-acetoxy-16,16-dimethyl-8-aza-D-homogona-1,3,5(10),9(11),13,17-hexaen-12-one, the product of acylotropic rearrangement at interaction of 16,16-dimethyl-8-aza-D-homogona-1,3,5(10),9(11),13-pentaene-12,17a-dione with acetic anthydride

On interaction of 16,16-dimethyl-8-aza-D-homogona-1,3,5(10),9(11),13-pentaene-12, 17a-dione with acetic anhydride acylotropic rearrangement occurs with the formation of a single product, viz. 17a-acetoxy-16, 16-dimethyl-8-aza-D-homogona-1,3,5(10),9(11),-13, 17a-hexaen-12-one. The effect of sodium acetate and of acetic acid concentration on the result of the reaction has been studied. The structure of the product was confirmed by data of elemental analysis, IR, UV,¹H, and¹³C NMR spectroscopy, mass spectrometry, and also X-ray structural analysis. Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Minsk 220141. Scientific Research Institute of Physicochemical Problems, Belarussian State University, Minsk 220080. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1376–1387, October, 1999.     

Perfluoro-1,3,5-tris(p-oligophenyl)benzenes: Amorphous Electron-Transport Materials with High-Glass-Transition Temperature and High Electron Mobility

Perfluoro-1,3,5-tris(p-quaterphenyl)benzene (PF-13Y) and perfluoro-1,3,5-tris(p-quinquephenyl)benzene (PF-16Y) have been synthesized and characterized. They showed higher glass transition temperatures compared with perfluoro-1,3,5-tris(p-terphenyl)benzene (PF-10Y). Organic light-emitting diodes were fabricated using these materials as the electron-transport layers. PF-13Y and -16Y are better electron transporters than PF-10Y. The electron mobilities of PF-10Y and Alq₃ were measured by the time-of-flight technique. PF-10Y showed higher electron mobilities (10⁻⁴ cm²/V s) and weaker electric field dependence compared with Alq₃.     

Structure and reactivity of steroids—VI : Long range effects in a series of Δ1,3,5(10)-estratriene compounds

The kinetics of the oxidation of 17β-hydroxy-Δ^1,3,5(10)-estratrienes which differ in D ring size, in C₃, substituent and in the character of fusion of the B and C rings by CrO₃ in AcOH has been studied. An increase in size of the D ring in the substrate diminishes reactivity of the 17β-hydroxy group in the oxidation. It has been found that the reactivities of the 17β and 17β-hydroxy groups of the Δ^1,3,5(10)-estratriene derivatives depend upon the electronic nature of the substituent at C³, explained by a long range effect operating from the A to D ring. The pK'a's of phenolic steroids have been measured and it was shown that introduction of the Δ⁸⁽⁹⁾ double bond increases the degree of dissociation of the phenolic hydroxyl. Expansion of the D ring and also reduction of the 17(17a)-keto group to 17β (17aβ) hydroxy group decreases the degree of dissociation of the phenolic hydroxyl as a result of the long range effect from the D to A ring. A linear correlation has been established between the oxidation and dissociation rate constants, confirming the existence of an interaction between C₃ and C_17(17a) at the expense of the long range effects from the A to D ring and vice versa. The long range effect apparently arises from a combination of inductive and conformational effects of the substituent. The kinetics of enzymic oxidation of 17β-hydroxy-Δ^1,3,5(10)-estratrienes by soluble 17β-estradiol dehydrogenase from human placenta has been investigated. In the case of 17β-hydroxy-Δ^1,3,5(10)-estratrienes of natural configuration, a linear correlation has been established between the values of the maximum rate constant and the oxidation rate constant. An assumption can thus be made about the major role of the contribution of the specific reactivity of the substrate to that of the enzyme-substrate complex, involving the size of the D ring and the long range effect of the substituent at C₃ upon the reaction center at C_17(17a). For 17β-hydroxy-Δ^1,3,5,(10)-estratrienes of the 8-isoconfiguration it is the specific reactivity of the substrate that makes the major contribution to the maximum rate values; this specific activity is a result of the substrate's configuration, which is responsible for the stability of the enzyme-substrate complex.     

Benzene ring assembly promoted by a camphor derived palladium complex

Trans-[PdCl₂L₂] (1, L=3-NNMe₂C₁₀H₁₄O), under mild reaction conditions, acts as a catalyst for the cyclic trimerization of alkynes. The best performance is achieved for the reaction with PhCCMe that affords 1,3,5-trimethyl-2,4,6-triphenyl benzene with high activity and selectivity (ca. 99%). As a general trend the catalytic activity is higher for internal (PhCCMe, PhCCPh) than for terminal alkynes (HCCPh, HCC^tBu, HCCCO₂Me). Under more drastic experimental conditions the reaction of 1 with PhCCPh yields trans-[PdCl₂(PhCCPh)₂] and no catalytic activity is observed. The molecular structure of 1,3,5-trimethyl-2,4,6-triphenyl benzene was confirmed by X-ray diffraction analysis. The molecules were characterized by ¹H- and ¹³C-NMR spectroscopies, FAB-MS and, in some cases, elemental analyses.     

Intramolekulare Diels-Alder-Additionen in 6-(But-3-enyl)-6-methyl-cyclohexa-2,4-dien-1-on-Systemen; eine neue Synthese von Twistanderivaten

Alkylation of the sodium salt of mesitol with 2-bromomethyl-buta-1,3-diene ( 7 ) in benzene and subsequent refluxing of the reaction mixture gave 7% 2-methylene-3-butenyl-mesitylether ( 8 ), 12% 5-methylene-1,3,8-trimethyl-tricyclo[4,3,1,0^3,7]-8-decen-2-one ( 9 ) and 44% 9-methylene-1,3,5-trimethyl-tricyclo[4,4,0,0^3,8]-4-decen-2-one ( 10 ), a twistane derivative. The same procedure, when applied to the sodium salt of 2,6-dimethyl-4-methoxyphenol, gave in 73% yield a 26:18:54 mixture of 2,6-dimethyl-4-methoxyphenyl-(2-methylene-3-butenyl)-ether ( 11 ), 1,3-dimethyl-8-methoxy-5-methylene-tricyclo[4,3,1,0^{3, 7}]-8-decen-2-one ( 12 ), and 1,3-dimethyl-5-methoxy-9-methylene-tricyclo[4,4,0,0^{3, 8}]-4-decen-2-one ( 13 ). The tricyclic ketones 9 and 10 , or 12 and 13 , were also obtained on heating 8 or 11 respectively at 176° in decane solution. Alkylation of the sodium salt of 2,6-dimethylphenol with 3-butenylbromide in boiling toluene gave 1,3-dimethyl-tricyclo[4,3,1,0^3,7]-8-decen-2-one ( 17 ) as the only tricyclic product in 8% yield. The structures of the twistane derivatives 10 and 13 as well as those of the ketones 9, 12 and 17 were mainly deduced from spectroscopic data. Furthermore, the ketones 10 and 13 could be converted to the twistane derivatives 20 and 22 , possessing C₂-symmetry. On the other hand, compounds 9 and 17 gave only the asymmetric derivatives 18 and 21 .     

Synthesis of 18,19-bisnor-δ1,3,5(10),13(17)-pregnapentaen-3-ol-20-one methyl ethek

Conclusions A method was developed for the synthesis of S-methoxy-^{1,3,5(10),13(17)}-D-homoestrapentaen-Ha-one, from which it was possible to obtain 3-methoxy-18,19-bisnor-_{1,3,5(10),13(17)}-pregnapentaen-20-one, a key compound in the total synthesis of 18-cyanosteroids.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 8, pp. 1844–1848, August, 1973.     

The total synthesis and anti-fertility activity of 6-silasteroids

4,4-Dimethyl-6-methoxy-4-sila-1-tetralone (2) was prepared by a modified literature procedure and converted to 3-methoxy-6,6-dimethyl-6-silaestra-1,3,5(10),8,14-pentaen-17β-yl acetate (5c). Catalytic hydrogenation of 5c gave 3-methoxy-6,6-dimethyl-6-silaestra-1,3,5(10),8-tetraen-17β-yl acetate (6b), and its 14-iso- and Δ^{1,3,5(10),8(14)} isomers, the proportions varying with the catalyst and solvent. Reduction of 6b with lithium-liquid ammonia, and O-demethylation, gave 6,6-dimethyl-6-silaestradiol (8b). Reduction of the 3-methyl ether of 8b with lithium-liquid ammonia-t-butanol and hydrolysis afforded 3-keto-6,6-dimethyl-6-silaestr-1(10)-en-17β-ol (15), which was catalytically reduced to its 1,10α-dihydro derivative 17. The 5,6 SiC bond of 8b, 15 and their derivatives was cleaved by boron tribromide, aq. ethanolic hydrogen fluoride, and other reagents, providing a series of 5,6-seco-6,6-dimethyl-6-silasteroids. X-ray crystallographic analysis of 17 and the 17α-ethynyl derivative of 15 confirmed the stereochemical assignments. None of the compounds which were subjected to uterotropic, anti-uterotropic, or post-coital assays, showed significant activity. A partially completed synthesis of 6-silaestradiol (21a) is described.     

Kinetics of the reactions of O3 and OH radicals with a series of dialkenes and trialkenes at 294 ± 2 K

Rate constants for the gas phase reactions of O₃ and OH radicals with 1,3-cycloheptadiene, 1,3,5-cycloheptatriene, and cis- and trans-1,3,5-hexatriene and also of O₃ with cis-2,trans-4-hexadiene and trans -2,trans -4-hexadiene have been determined at 294 ± 2 K. The rate constants determined for reaction with O₃ were (in cm³ molecule^-1s^?1 units): 1,3-cycloheptadiene, (1.56 ± 0.21) × 10^-16; 1,3,5-cycloheptatriene, (5.39 ± 0.78) × 10^?17; 1,3,5-hexatriene, (2.62 ± 0.34) × 10^?17; cis?2,trans-4-hexadiene, (3.14 ± 0.34) × 10^?16; and trans ?2, trans -4-hexadiene, (3.74 ± 0.61) × 10^?16; with the cis- and trans-1,3,5-hexatriene isomers reacting with essentially identical rate constants. The rate constants determined for reaction with OH radicals were (in cm³ molecule^?1 s^?1 units): 1,3-cycloheptadiene, (1.31 ± 0.04) × 10^?10; 1,3,5-cycloheptatriene, (9.12 × 0.23) × 10^?11; cis-1,3,5-hexatriene, (1.04 ± 0.07) × 10^?10; and trans 1,3,5-hexatriene, (1.04 ± 0.17) × 10^?10. These data, which are the first reported values for these di- and tri-alkenes, are discussed in the context of previously determined O₃ and OH radical rate constants for alkenes and cycloalkenes.     

New analogs of steroid estrogens

Aiming at the investigation of the mechanism of functioning of steroid estrogens a series of compounds with unnatural rings junction was synthesized. All investigated compounds exhibit a reduced uterotropic activity. It was established applying the NMR spectroscopy that 7α-methyl-3-methoxy-D-homo-6-oxa-8α,14β-estra-1,3,5(10)-trien-17a-one existed in solution in two conformations distinguished by the structure of the rings B, C, and D simultaneously. The reaction of 17-methylidene-3-methoxy-6-oxa-8α-estra-1,3,5(10)-triene with hydrobromic acid in acetic acid promotes a rearrangement with the migration of a methyl group into the position 17 resulting in the formation of 17,17-dimethyl-6-oxa-8α-gona-1,3,5(10),13(14)-tetraene derivatives.     

Heterocyclic synthesis using nitrilimines: Part 19. Synthesis of novel 1,3,5-trisubstituted-1,2,4-triazoles

This paper describes the synthesis of a new series of 1,3,5-trisubstituted-1,2,4-triazoles by 1,3-dipolar cycloaddition reaction of C-phenyl-aminocarbonyl-N-arylnitrilimines with guanidine derivatives. The structures of the newly synthesized compounds were elucidated by spectral methods (IR, ¹H NMR, ¹³C NMR and MS spectroscopy) and elemental analysis. The microbial features of the synthesized compounds were studied using well-established methods from the literature.     

△^9^(^1^1^)-雌甾四烯类化合物的硼氢化-铬酸氧化 II

雌甾-11-酮化合物是合成具有强效抗生育活性11-烃基取代在甾体化合物的关键中间体。本文对13β-乙基-3-甲氧基-甾-1,3,5(10), 9(11)-四烯-17β-醇的硼氢化-铬酸氧化反应进行研究, 结果发现产物比较复杂, 在温和条件下, 主要产物为13β-乙基-3-甲氧基-甾-1,3,5(10)-三烯-17-酮-112-硼酸, 增加氧化剂用量, 延长反应时间则得到11,17-二酮。     

Structural analysis and biomedical potential of novel salicyloyloxy estrane derivatives synthesized by microwave irradiation

New estrane salicyloyloxy or D-homo derivatives were synthesized under microwave (MW) or conventional heating from estrane precursors and methyl salicylate. The MW technique provides advantages regarding product yield and reaction time, and represents a more environmentally friendly approach than conventional heating. Considering the biomedical potential of estrane compounds, we evaluated the antioxidant activity and cytotoxicity of synthesized estrane derivatives in a series of in vitro tests, as well as their 3β-hydroxysteroid dehydrogenase/Δ⁵ → Δ⁴ isomerase (3βHSD) and 17β-hydroxysteroid dehydrogenase types 1, 2 and 3 (17βHSD1, 17βHSD2 and 17βHSD3) inhibition potentials. In DPPH tests, 3-methoxyestra-1,3,5(10)-trien-17β-yl salicylate displayed antioxidant potential, while all compounds exhibited OH radical neutralization activity. 3-Oxoestr-4-en-17β-yl salicylate showed strong cytotoxicity against MDA-MB-231 breast cancer cells, while 17-oxoestra-1,3,5(10)-trien-3-yl salicylate, estra-1,3,5(10)-triene-3,17β-diyl 3-benzoate 17-salicylate and 3-benzyloxy-17-salicyloyloxy-16,17-secoestra-1,3,5(10)-triene-16-nitrile showed the strongest inhibition of PC-3 prostate cancer cell growth. 3-Hydroxyestra-1,3,5(10)-trien-17β-yl salicylate was the best inhibitor of 17βHSD2, suggesting potential use in treating pathological conditions associated with estrogen depletion. For 3-methoxyestra-1,3,5(10)-trien-17β-yl salicylate and 3-oxoestr-4-en-17β-yl salicylate, X-ray crystal structure analysis and molecular energy optimization were performed to define their conformations and energy minima. Very good overlap in the region of the steroidal nucleus was observed for the molecular structures of each analyzed molecule in the crystalline state and after energy optimization, while conformer analysis indicates conformational flexibility in the form of rotation around the C17···O2 bond. Structural geometry analysis for these compounds shows that the region of ring A in steroids, and especially the C3 atom functional group, is important structural features concerning antiproliferative activity against MDA-MB-231 cells.

     

Synthesis and characterization of 1,3,5-tris((1/2<Emphasis Type="Italic">H</Emphasis>-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione

2,2′,2″-(2,4,6-Trioxo-1,3,5-triazinane-1,3,5-triyl) triacetonitrile (or tris-(cyanomethyl)-isocyanurate) and 1,3,5-tris((1/2H-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione (or tris-(5-tetrazolylmethyl)-isocyanurate) were synthesized with new methods. High yields, simple methodology, and cheapness are advantages of the methods. Furthermore, 1,3,5-tris((1/2H-tetrazol-5-yl)methyl)-1,3,5-triazinane-2,4,6-trione was synthesized in the less hazardous condition. The compounds were characterized by elemental analysis, IR, ¹HNMR, ¹³CNMR and mass spectroscopic analysis. In addition, DSC/TGA measurements were carried out to determine the thermal behavior of the final product.     

Synthesis of 19,B-Bisnoranalogs of Steroid Androgens with cis-Fused B and C Rings

Reduction by Birch procedure of 3-methoxy-B-nor-8-isoestra-1,3,5(10)-trienes followed by hydrolysis of reaction products furnished 19,B-bisnor-8,10-isoanalogs of steroid androgens. With the use of the correlation NMR spectroscopy a complete assignment of signals in the ¹H and ¹³C NMR spectra was performed for two representatives of this steroid group, and their prevailing conformations in solution were established.     

Accessing highly electron-rich calix[n]arene (n = 4 and 8) derivatives from acid-catalyzed condensation of 1,3,5-tripropoxybenzene

Synthesizing novel electron-rich calix[n]arene derivatives to alter the electronic properties of calixarene-based materials has been one of the long-standing interests. Herein, two new electron-rich calix[n]arenes (n = 4 and 8) with different sizes were synthesized by acid-catalyzed condensation reaction of 1,3,5-tripropoxybenzene and paraformaldehyde. Both derivatives were fully characterized with ¹H and ¹³C NMR, mass spectrometry and X-ray crystallography. Furthermore, their electrochemical properties and oxidized product (cation radicals) have also been investigated.     

Analysis of anomalous vibrational and rotational distributions in the CN(B2Σ+) state produced in the reaction of Ar(3P0,2) metastables with BrCN

The CN(B²Σ⁺ - X²Σ⁺) tail band emission system for μ′ = 11–20 resulting from the energy transfer reaction Ar(³P_0,2) + BrCN in a flowing afterglow apparatus was measured. The vibrational and rotational distributions were determined as a function of argon pressure. Numerous perturbed rotational lines were observed; analysis of the dependences of these lines on argon pressure, with the aid of experimental information already published, led to the following assignments as to the origins of the perturbations: For μ′ = 11, N′ = 20 and μ′ = 13, N′ = 9, the perturbing state is a ⁴Σ⁺; for μ′ = 12, N′ = 10 and 14, μ′ = 14, N′ = 7 and 10, and μ′ = 17, N′ ≈ 17–19 the perturbing state is A ²Π_i. The perturbed rotational line, μ′ = 11, N′ = 20, is found to be the primary source of intensity in the μ′ =11 vibrational band, but in all other cases the perturbed rotational lines do not significantly aid in the populating of the vibrational state. The anomalously high vibrational populations found in the tail band emission system (μ′ = 12, 14, 17 and 18), as well as the significantly high rotational excitations observed in the μ′ = 12–20 vibrational bands, apparently arise directly from the reaction intermediate.     

Nitrene-carbene rearrangement during photolysis of 2-azido-1,3,5-triazines in argon matrices

It was shown using IR spectroscopy and ESR spectroscopy that UV irradiation of 2-azido-4,6-dichloro-1,3,5-triazine isolated in solid argon resulted in triplet 4,6-dichloro-1,3,5-tri-azinyl-2-nitrene (D = 1.384 cm^?1, E = 0.004 cm^?1), whose further photochemical transformation included the consecutive formation of 3-didehydro-1,2,4,6-tetraazepine, 2-chloro-1-diazochloromethyl-2-isocyanocarboimide, and presumably triplet 2-chloro-1-chloromethyl-idene-2-isocyanocarboimide and isocyanodichloroacetonitrile. The photolysis of 2-azido-4,6-dimethoxy-1,3,5-triazine and 2-azido-4,6-di(dimethylamino)-1,3,5-triazine affords photo-chemically stable triplet 4,6-dimethoxy-1,3,5-triazinyl-2-nitrene (D = 1.436 cm^?1, E = 0.0044 cm^?1) and 4,6-bis(dimethylamino)-1,3,5-triazinyl-2-nitrene (D = 1.468 cm^?1, E = 0.0042 cm^?1) as the final products.     

Steroide—XLIV : 1H-NMR-untersuchungen. Konfigurationszuordnung 16,17-disubstituierter steroide

¹H-NMR-spectra of 16,17-disubstituted estra-1,3,5(10)-trienes and androstanes are discussed with regard to the determination of the configuration in the positions 16 and 17. The availability of the coupling constant J_16,17, the chemical shift of the 13β-methyl protons, the chemical shift of the 17-proton and both the chemical shift and the sum of the coupling constants of the 16-proton is investigated for the elucidation of unknown configurations at C-16 and C-17. 16β,17α-Configuration of the substituents was found to be distinguished from the other three configurations by a low coupling constant J_16,17 (≦2 Hz). For the determination of the other configurations the coupling constant J_16,17 was also used together with the other data. Esterification of the 17-hydroxy group or its reaction with trichloracetylisocyanate caused a low field shift of the 17-proton depending on the configuration of the substituents in the positions 16 and 17. This is an additional possibility for the configurational assignment.     

Magnetic circular dichroism of some benzene derivatives

The MCD spectra of phloroglucin, 1,3,5-trimethoxybenzene, 1,3,5-tricyanobenzene, 1,3,5-trinitrobenzene, 1,3,5-benzenetricarboxylic acid and 1,3,5-benzenetricarbonyl chloride were measured. For the ¹E′ ← ¹A′₁ transition of phloroglucin or 1,3,5-tricyanobenzene and the ¹E′ ← ¹A′ transition of 1,3,5-trimethoxybenzene, the Faraday A term was observed and the A/D value was extracted. However, 1,3,5-trinitrobenzene, 1,3,5-benzenetricarboxylic acid and 1,3,5-benzenetricarbonyl chloride showed no magnetic circular dichroism in this spectral region. The magnetic moments in the ¹E′ states of these molecules seem to be quenched by the effects of substituents. The magnetic moments in the ¹E′ states of benzene derivatives are sensitive to substitution in the benzene ring.     

Synthesis in the diazasteroid group. III . Syntheses of the 8,16- and 8,17-diazasteroid systems

By using 3-pyrrolidone derivatives as a source of the D ring, the following five diazasteroids were synthesized: 8,16-diaza-2,3-dimethoxy-15,15,16-trimethylgona-1,3,5(10),13-tetraen-12-one (VII), 8,16-diaza-2,3-dimethoxy-16-acetylgona-1,3,5(10),13-tetraen-12-one (X), 8,17-diaza-2,3-dimethoxy-17-acetylgona-1,3,5(10),13-tetracn-12-one (XI), 8,16-diaza-16-acetylgona-1,3,5(10), 13-tetraen-12-one (XII), and 8,17-diaza-17-acetylgona-1,3,5(10),13-tetraen-12-one (XIII).