β-Fur-2-yl-α-halogenacrylonitrile. I. Darstellung von β-Fur-2-yl-ß-aminoacrylonitrilen und β-Fur-2-yl-α-aminoacrylonitrilen

β-Fur-2-yl-α-halogenacrylonitriles. I. Preparation of β-Fur-2-yl-ß-aminoacrylonitriles and β-Fur-2-yl-α-aminoacrylonitriles β-Fur-2-yl-α-halogenacrylonitriles 1 react with secondary amines to yield β-fur-2-yl-ß-aminonitriles 2 and β-fur-2-yl-α-aminoacrylonitriles 3 . The ¹ H-n.m.r. spectra of the E/Z isomers are discussed.     

Furylvinylhalogenide. X [1]. Reaktionen von β-Fur-2-yl-β-chlor-α-cyanacrylsäurederivaten mit Hydrazinen

Furylvinylhalides. X. Reactions of β-Fur-2-yl-β-chloro-α-cyanoacrylic Acid Derivatives with Hydrazines β-Fur-2-yl-β-chloro-α-cyanoacrylic acid derivatives 3 react with hydrazines yielding 3-fur-2-yl-5-aminopyrazoles 5 or 3-fur-2-yl-4-cyanpyrazolin-5-ones 6 . In some cases the β-hydrazino-α-cyanoacrylic acid derivatives 4 , could be isolated.     

β-Fur-2-yl-α-halogenacrylonitrile. IV. Reaktionen von β-Fur-2-yl-α-halogenacrylonitrilen mit Alkoholen und Phenolen

β-Fur-2-yl-α-halogenacrylonitriles. IV. Reactions of β-Fur-2-yl-α-halogenacrylonitriles with Alcohols and Phenols β-Fur-2-yl-α-halogenacrylonitriles 1a – c react with alcohols and phenols to yield β-fur-2-yl-β-alkoxyacrylonitriles and β-fur-2-yl-β-aroxyacrylonitriles 2a – k respectively. With ethylene glycol α-[2-(fur-2-yl)-1, 3-dioxolan-2-yl]acetonitriles 3a, b are formed.     

Synthesen von β-Fur-2-yl-α-halogenacrylonitrilen

Syntheses of β-Fur-2-yl-α-halogenacrylonitriles Syntheses of β-fur-2-yl-α-halogenacrylonitriles 2a–f by Wittig-olefination of furfurales, Hunsdiecker-reaction of β-(5-nitro-fur-2-yl)-α-cyanoacrylic acid 3 , halogenation of β-fur-2-yl acrylonitriles and reaction of furfurales with β-azido-α-halogen-γ-methoxy-Δ^α,β-crotonolactones 9 are described.     

β-Fur-2-yl-α-halogenacrylonitrile. VII. Reaktionen von β-(5-Brom-fur-2-yl)-α-bromacrylonitril mit Mercaptan,Thioharnstoff und Thioharnstoffderivaten

β-Fur-2-yl-α-halogenacrylonitriles. VII. Reactions of β-(5-Bromo-fur-2-yl)-α-bromoacrylonitriles with Mercaptans, Thiourea and Thiourea Derivatives β-(5-Bromo-fur-2-yl)-α-bromoacrylonitrile 1 reacts with ethylmercaptan to yield β-(5-bromo-fur-2-yl) β-ethylthioacrylonitrile 3 . With thiourea β,β′-thio-bis[β-(5-bromo-fur-2-yl)]-acrylonitrile 2 is formed. The pyrimidines 4 and 5 have been prepared by the reaction of 1 with s-methylthiourea and 2-aminothiazole, respectively. The structure of the new compounds were determined by means of x-ray analysis, ¹H-n.m.r., ¹³C-n.m.r. and mass-spectroscopy.     

β-Fur-2-yl-α-halogenacrylonitrile. VIII. Konformationsuntersuchungen an substituierten β-Fur-2-yl-acrylonitrilen

β-Fur-2-yl-β-halogenacrylonitriles. VIII. Investigations of the Conformation of Substituted β-Fur-2-yl-acrylonitriles X-ray analysis, n.m.r.-investigations in the presence of Eu(FOD)₃ and NOE-measurement indicate, that the E-isomer of β-substituted β-fur-2-yl-acrylonitriles exist in the s-cis conformation, whereas the E-isomer of the α-substituted β-fur-2-yl-acrylonitriles prefer the s-trans-conformation. The influence of the configuration and conformation on the chemical shift of the H-3-furan protons is discussed.     

β-Fur-2-yl-α-halogenacrylonitrile. V [1] Darstellung von β-(5-Nitro-fur-2-yl)-α-azidoacrylonitril und β-(5-Nitro-fur-2-yl)-α-aminoacrylonitril

β-Fur-2-yl-α-halogenacrylonitriles. V. Preparation of β-(5-Nitro-fur-2-yl)-α-azidoacrylonitrile and β-(5-Nitro-fur-2-yl)-α-aminoacrylonitrile β-(5-Nitro-fur-2-yl)-α-chloroacrylonitrile ( 1 ) reacts with sodium azide to yield β-(5-nitro-fur-2-yl)-α-azidoacrylonitrile ( 2 ). By Staudinger-reaction β-(5-nitro-fur-2-yl)-α-aminoacrylonitrile ( 5 ) is formed. The ¹H- and ¹³C-n.m.r. spectra of E/Z isomers are discussed.     

Intermediates of Prostanoid Synthesis. Stereospecific conversion of (+)-5β-hydroxycyclopenten-2-yl-1β-acetic acid γ-lactone into (+)-1β-methoxycarbonylmethyl-2β,3β-(p-nitrobenzylidene)-dioxycyclopentan-5-one

Starting from (+)-5β-hydroxycyclopenten-2-yl-1β-acetic acid γ-lactone ( 1 ), (+)-1β-methoxycarbonylmethyl-2β, 3β-(p-nitrobenzylidene)-dioxycyclopentan-5-one ( 7 ) was prepared within 4 steps. Subsequent cleavage of the latter gives (−)-3β-hydroxy-1-methoxy-carbonylmethylcyclopent-1-en-5-one ( 8a ). Hydroxylation of the lactone ( 1 ) was found to give (+)-2β,3β,5β-trihydroxycyclopentyl-1β-acetic acid γ-lactone ( 2a ) with cis-oriented hydroxy groups in respect to the lactone ring. No formation of the trans-isomer, as has been reported earlier [4], was observed.     

Steroide. XLVI. Darstellung von 15.16.17-trisubstituierten Steroiden durch Ringöffnung von 17β-substituierten 15β.16β-Epoxy-östra-1.3.5(10)-trien-3-methyläthern

Steroids. XLVI. Preparation of 15,16,17-Trisubstituted Steroids by Ring Cleavage of 17β-Substituted 15β,16β-Epoxy-estra-1,3,5(10)-triene 3-Methylethers The ring cleavage of 15β.16β-epoxy-3-methoxy-estra-1-3,5(10)-triene-17β-ol 1a with strong nucleophiles occurs mainly at C-16, yielding 16α-substituted 15β,17β-diols 2a–f . Besides this, 1a is cleaved to a small extent at C-15, yielding the 15α-substituted 16β,17β-diols 3a—f and the Δ¹⁴-16,17β-diol 5a . The structures have been elucidated by means of i.r., H-n.m.r. and mass spectroscopy.     

13C-NMR-Spektroskopie von bromierten 3-Keto- und 3β-Acetoxy-5α-cholestan-Verbindungen

¹³C-NMR Spectroscopic Investigations of Brominated 3-Keto- and 3β-Acetoxy-5α-cholestane Derivatives The chemical shifts of some brominated 3-keto- and 3β-acetoxy-5α-cholestane derivatives are determined. The substituent effects of bromine atoms on chemical shifts (SCS) and their additive behaviour, especially γ-SCS, are discussed.     

β-Thiocyanatovinylcarbonylverbindungen. III. 1H-NMR-Untersuchungen an β-Thiocyanato-vinylaldehyden

β-Thiocyanato-vinyl-carbonyl Compounds. III ¹H-NMR Investigations of β-Thiocyanato-vinylaldehydes The ¹H-NMR spectra of some alkyl- and phenylsubstituted Z/E-isomeric β-thiocyanato-vinylaldehydes are represented. The assignment for Z/E-isomers is made using the chemical shifts of the CHO-protons and paramagnetic shift experiments. The discussion of the ΔEu-values allows to determine the conformation of the CHO-group. The main products in the case of the alkyl-substituted β-thiocyanato-vinylaldehydes are the Z-isomeric compounds which fact is attributed to mechanistic and electronic effects.     

New Intermediates and Dyes for Synthetic-polymer Fibres Derivatives of 2-Chloro-4-nitro-4‘-(N-β-hydroxyethyl-N- β-cyanoethylamino)azobenzene

Condensation of 2-chloro-4-nitro-4^t-(N-(β-hydroxyethyl-N-β-cy anoethylamino)azobenzene with various acid chlorides, chloroformates, isocyanates, isothiocyanates and reactive halogeno compounds gives dyes of excellent fastness to light and sublimation on polyester fibres.     

3β-Chlorsteroide – Ernährungsphysiologische und toxikologische Eigenschaften in Mäusen

3β-Chlorosteroids - Nutritional and Toxicological Effects in Mice 3-Chlorosteroids, e.g. 3-chlorocholest-5-ene and 3-chlorostigmast-5-ene, are formed from the corresponding sterols during the industrial hydrolysis of proteins for the production of flavor enhancers. In future, these compounds may also attract attention as environmental contaminants. A simple method for the fractionation and quantitative determination of 3β-chlorosteroids by C₁₈ reversed-phase HPLC has been developed and used for the analysis of these chlorinated steroids in protein hydrolysates. In addition, the biological effects of orally administrated 3β-chloro-steroids were tested in mice that were fed 3β-chlorocholest-5-ene and 3β-chlorostigmast-5-ene in doses of 1 and 10 mg/animal/day. The results of our study showed that body and organ weights as well as feed intake of the various experimental groups were not significantly different from those of the control group. The quantitative determination of 3β-chlorosteroids in organs and tissues revealed that intestinal absorption of 3β-chlorocholest-5-ene was higher than that of 3β-chlorostigmast-5-ene. Highest concentration of 3β-chlorocholest-5-ene was detected in liver and adipose tissue. Absorption and distribution in tissues as well as metabolism of both radioactive 3β-chloro-[4-¹⁴C]cholest-5-ene and 3β-chloro-[4-¹⁴C]stigmast-5-ene have also been studied in mice. At 2 hours after stomach incubation of the two substrates, large proportions of radioactivity had passed through the small intestine and were concentrated in the contents of caecum and colon. Only small proportions of radioactivity were detected outside the alimentary canal, predominantly in the liver. Histopathological examination of sections of organs and tissues such as stomach, duodenum, liver, kidneys, and spleen showed no indications of irreversible cell damages caused by 3β-chlorosteroids.     

Reaktionen von β-Chlorvinylaldehyden. V [1]. Zur Bildung von 2,2′-Thiopyrylotrimethinfarbsalzen aus 2-(α-Formylalkyliden)-2H-thiopyranen

Reactions of β-Chlorovinylaldehydes. V. The Formation of 2,2′-Thiopyrylocyanine Dyes from 2-(α-Formylalkylidene)-2H-thipyranes Substituted β-chlorocrotonaldehydes react with Na₂S · 9H₂O to form 2-(α-formyl-alkylidene)-2H-thiopyranes 1 . The corresponding thiopyrylium salts 2 which are easily available from 1 and strong acids exist in the enolic form (2-β-hydroxyvinyl-thiopyrylium salts). They are converted at room temperature in methanol solution to dark green compounds, which are identified as 2,2′-thiopyrylotrimethincyanine dyes 3 . The mechanism of formation of compounds 3 is discussed.     

Darstellung von schwer entflammbaren polymeren unter verwendung von β-trichlormethyl-β-lactonen und deren derivate

By using β-trichloromethyl-β-lactones it is possible to incorporate the CCl₃-group into various classes of polymers. This can be achieved either via ringopening copolymerization or by using the adducts of these lactones with amines, alcohols or phenols in polycondensation or polyaddition reactions. Under suitable reaction conditions block- or graft-copolymers can be obtained. Finally, derivatives of β-trichloro-β-propiolactones can be used for the incorporation into polymers after or during polymerization. Polymers containing CCl₃-groups are flame resistant or selfextinguishing. Often, these effects are observed at lower chlorine contents than normally necessary with other chlorinated flame retardants.     

β‐Aminopeptidase‐Catalyzed Biotransformations of β2‐Dipeptides: Kinetic Resolution and Enzymatic Coupling

We have previously shown that the β‐aminopeptidases BapA from Sphingosinicella xenopeptidilytica and DmpA from Ochrobactrum anthropi can catalyze reactions with non‐natural β³‐peptides and β³‐amino acid amides. Here we report that these exceptional enzymes are also able to utilize synthetic dipeptides with N‐terminal β²‐amino acid residues as substrates under aqueous conditions. The suitability of a β²‐peptide as a substrate for BapA or DmpA was strongly dependent on the size of the C_α substituent of the N‐terminal β²‐amino acid. BapA was shown to convert a diastereomeric mixture of the β²‐peptide H‐β²hPhe‐β²hAla‐OH, but did not act on diastereomerically pure β²,β³‐dipeptides containing an N‐terminal β²‐homoalanine. In contrast, DmpA was only active with the latter dipeptides as substrates. BapA‐catalyzed transformation of the diastereomeric mixture of H‐β²hPhe‐β²hAla‐OH proceeded along two highly S‐enantioselective reaction routes, one leading to substrate hydrolysis and the other to the synthesis of coupling products. The synthetic route predominated even at neutral pH. A rise in pH of three log units shifted the synthesis‐to‐hydrolysis ratio (v_S/v_H) further towards peptide formation. Because the equilibrium of the reaction lies on the side of hydrolysis, prolonged incubation resulted in the cleavage of all peptides that carried an N‐terminal β‐amino acid of S configuration. After completion of the enzymatic reaction, only the S enantiomer of β²‐homophenylalanine was detected (ee>99 % for H‐(S)‐β²‐hPhe‐OH, E>500); this confirmed the high enantioselectivity of the reaction. Our findings suggest interesting new applications of the enzymes BapA and DmpA for the production of enantiopure β²‐amino acids and the enantioselective coupling of N‐terminal β²‐amino acids to peptides.     

Zur Synthese CF3-substituierter Chinoline aus β-Chlor-β-trifluormethyl-vinylaldehyden. I

Synthesis of CF₃-Substituted Quinolines from β-Chloro-β-trifluoromethyl-vinylaldehydes. I 3-(Trifluoromethyl)-acroleines 2 have been synthesized through VILSMEIER's reaction from α-Trifluoro-methylketones 1 . The reaction of 2 with anilines and naphthylamines gives in good yields 2-trifluoromethylquinolines 4 and benzoquinolines 5 .     

Studies of the Ramberg-Bäcklund Rearrangement. Part I. Rearrangement of α-Bromo-β-Keto- and α-Bromo-α-Carbethoxy-Sulphones

α-Bromosulphones, carrying negative substituents (keto or carbethoxy-groups) next to the bromine atom, undergo the Ramberg-Bäcklund rearrangement and give α,β-unsaturated ketones and esters. β-Disulphones are converted into α, β-unsaturated sulphones under these conditions.     

Herstellung und Charakterisierung der Sulfamate von Estra-3,17ξ-diolen. Schnelle Umsetzung von 16α-Fluorestradiol zum 16α-Fluorestradiol-3,17β-disulfamat

Estradiols are able to form two monosulphamates and one disulphamate. In the present work all the sulphamates of 17α-estradiol, 17β-estradiol and 16α-fluoroestradiol were synthesized and characterized. For characterization NMR spectroscopy was used first of all. Because of its high sulphatase inhibitory efficiency 16α-fluoroestradiol-3,17β-disulphamate found a special interest among the new sulphamates. Just the binding between sulphamate and sulphatase favoured 16α-[^18F]fluorestradiol-3,17β-disulphamate to a new radio-pharmaceutical which should be appropriate to image the active sites of sulphatase by positron emission tomography. The preparation of 16α-[¹⁸F]fluoro-estradiol-3,17β-disulphamate requires a simple and rapid procedure. The conditions for such a procedure were also elaborated using non-radioactive substances.     

Steroide. XLVIII. 16α-Heterosubstituierte Östradiol-3-methyläther

Steroids. XLVIII. 16 α-Heterosubstituted 3-Methoxy-estra-1,3,5(10)-triene-17β-ols The synthesis of 16α-heterosubstituted 3-methoxy-estra-1,3,5(10)-triene-17β-ols 2a—2e from 16β-bromo-3-methoxy-estra-1,3,5(10)-triene-17β-ol 1 by substitution with nucleophiles is described. Additional compounds of this class 2f—2h are obtained by transformation of the new 16α-substituents. Jones oxidation of 2b and 2c yields the 17-keto compounds 3b and 3c . The configuration of the new compounds is confirmed by i.r. and ¹H n.m.r. spectra.