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.     

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.     

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.     

Furylvinylhalogenide. IX. Reaktionen von β-Fur-2-yl-β-chlor-α-cyanacrylsäureestern mit Aminen

Furylvinylhalides. IX. Reactions of β-fur-2-yl-β-chloro-α-cyanoacrylates with amines β-Fur-2-yl-β-chloro-α-cyanoacrylates 4 react with amines to yield β-Fur-2-yl-β-amino-α-cyanoacrylates 5 . The ¹H-n.m.r. spectra of 5 are discussed.     

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-Thiocyanatovinylcarbonylverbindungen. II. Darstellung von 4,5-substituierten Isothiazolen

β-Thiocyanato-vinylcarbonyl Compounds. II. Preparation of 4,5-Substituted Isothiazoles Z-β-Thiocyanato-vinylaldehydes cyclize with liquid ammonia to isothiazoles. A new synthesis for 4- and/or 5-alkyl, cycloalkyl- or aryl-substituted isothiazoles by direct reaction of Z/E-β-chlorovinylaldehydes with ammonium thiocyanate in boiling acetone is presented. As a third procedure, the reaction of β-thiocyanato-vinylaldehydes with NH₄SCN in acetone is convenient. The obtained 4,5-substituted isothiazoles were characterized by their u. v. and n. m. r. spectra and perchlorates.     

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.     

β-Ketoester — a Rearranged Product of Epoxidation of α, β-Unsaturated Methyl Ester

Attempted epoxidation of long-chain α,β-unsaturated esters resulted in the formation of the rearranged products of the corresponding epoxyesters. It was observed that reaction of peracids with esters of C₁₆, C₁₈ and C₂₂ trans-2-enoic acids, instead of yielding the expected epoxides, gave the isomerized products characterized as β-ketoesters. The structure of β-ketoester as saturated 3-oxoester was unambiguously established by chemical methods as well as by IR, NMR and Mass spectrometry. The selectivity of this rearrangement provides a useful synthetic pathway for the preparation of β-ketoesters.     

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 .     

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.     

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.     

Vinyloge Acylverbindungen. XX. Reaktivität und Toxizität arylsubstituierter β-Chlorvinylketone, β-Chlorvinylaldehyde und β-Chlorvinylmethyleniminiumsalze

Vinylogous Acyl Compounds. XX. Reactivity and Toxicity of Aryl-substituted β-Chlorovinyl Ketones, β-Chlorovinyl Aldehydes, and β-Chlorovinyl Methyleniminium Salts Based on kinetic measurements, the nucleophilic replaceability of the chlorine in aromatic β-chlorovinyl ketones ArCO-CH  CH-Cl ( 1 ), isomeric β-chlorovinyl aldehydes OCH CHC(Cl)Ar( 2 ), and corresponding β-chlorovinyl methyleniminium salts Me₂N^⊕;CH CHC(Cl)Ar X^⊖ ( 3 ) is compared and related to toxicological findings. The chemical reactivity of these important synthetic building blocks increases in the order 2 < 1 < 3 , the acute toxicity (24 h LD₅₀ i. p. in the mouse) shows the graduation 2 < 3 < 1 . Compounds of type 1 prove to be relatively toxic (LD₅₀ 24–42 mg/kg) and display a marked necrotic action after percutaneous absorption, whereas the aldehydes 2 have not only a minor acute toxicity (LD₅₀ 158–298 mg/kg) but also a somewhat less marked skin damaging activity. In addition, the LD₅₀ values of selected β-chlorovinyl carbonyl compounds are compared with those of corresponding halogen-free compounds as well as of vinylogous carbonamidium salts ArCO CHCH N^⊕R₃X^⊖. The latter, which can be used as synthetic equivalents of 1 , differ in both the reduced acute toxicity and missing skin damaging properties.     

Studies on diastereoselective additions of 2-substituted cyclopentanones to β-nitrostyrene

The Michael addition of 2-substituted cyclopentanones 1 to β-nitrostyrene 2 proceeds at room temperature in the presence of catalysts such as NEt₃, DMAP, KOAc, or Ni(acac)₂ leading to 2-substituted 2-(2-nitro-1-phenylethyl)cyclopentanones 3/4 . Depending on substituents R in 1 compounds rac- 3/4 may be obtained with high diastereoselectivity. The influences of reaction conditions were studied and the diastereomeric ratio was determined by means of ¹H-NMR spectroscopy. In the cases of rac- 3/4a-c , rac- 3g–i , rac- 3k , the diastereomers could be isolated in pure form. The configuration of compounds rac- 3a , rac- 4a was established from X-ray crystallography.     

Reaktivität und Selektivität bei der Oxidation von Styrolderivaten. IV. Untersuchungen zur Oxidation von substituierten β,β-Dimethylstyrolen

Reactivity and Selectivity in the Oxidation of Styrene Derivatives. IV. Studies on the Oxidation of Substituted β,β-Dimethylstyrenes The liquid phase oxidation of substitued (p-MeO-, p-Cl-, m-CF₃-) 2-aryl-3-methyl-but-2-enes, of 1,1-diphenyl-2-methyl-propene, of 1-ethoxy-2-methyl-1-phenyl-propene and of 9-isopropylidene-fluorene with pure oxygen was investigated in chlorobenzene solution and in presence of cumene and of cumene hydroperoxide in the temperature range 65-125 °C. The product yields were determined gaschromatographically. The differences of the activation energies of epoxide formation and the parallel reactions were calculated. They amount to 19–48 kJ/mol. The epoxide selectivity increases with increasing temperature and increasing concentration of olefin. The relative chain propagation constants (k_{pC C}) were determined by competitive oxidation with cumene. The k_{pC C} values of substitued β,β-dimethylstyrenes can be correlated by a LFE-relationship with the ionisation energies of the olefins.     

On the Crystal Structure of the β′1-Form of Triglycerides and the Mechanism behind the β′1 → β Transition of Fats

Based on earlier single crystal studies ^1,2 new interpretation of the crystal structure of the stable β′-form (β′₁) is proposed. This new interpretation gives the possibility to discuss the β′₁-form of various triglycerides. A mechanism behind the β′₁ → β transition is proposed. This mechanism is based on differences in the methyl end group region and supported by X-ray diffraction studies.     

Acetylcholine Promotes Binding of α‐Conotoxin MII at α3β2 Nicotinic Acetylcholine Receptors

α‐Conotoxin MII (α‐CTxMII) is a 16‐residue peptide with the sequence GCCSNPVCHLEHSNLC, containing Cys2–Cys8 and Cys3–Cys16 disulfide bonds. This peptide, isolated from the venom of the marine cone snail Conus magus, is a potent and selective antagonist of neuronal nicotinic acetylcholine receptors (nAChRs). To evaluate the impact of channel–ligand interactions on ligand‐binding affinity, homology models of the heteropentameric α₃β₂‐nAChR were constructed. The models were created in MODELLER with the aid of experimentally characterized structures of the Torpedo marmorata‐nAChR (Tm‐nAChR, PDB ID: 2BG9) and the Aplysia californica‐acetylcholine binding protein (Ac‐AChBP, PDB ID: 2BR8) as templates for the α₃‐ and β₂‐subunit isoforms derived from rat neuronal nAChR primary amino acid sequences. Molecular docking calculations were performed with AutoDock to evaluate interactions of the heteropentameric nAChR homology models with the ligands acetylcholine (ACh) and α‐CTxMII. The nAChR homology models described here bind ACh with binding energies commensurate with those of previously reported systems, and identify critical interactions that facilitate both ACh and α‐CTxMII ligand binding. The docking calculations revealed an increased binding affinity of the α₃β₂‐nAChR for α‐CTxMII with ACh bound to the receptor, and this was confirmed through two‐electrode voltage clamp experiments on oocytes from Xenopus laevis. These findings provide insights into the inhibition and mechanism of electrostatically driven antagonist properties of the α‐CTxMIIs on nAChRs.     

Structure-activity relations of β-adrenergic agents

A review of the structure-activity relations in aryloxypropanolamine β-adrenoceptor drugs is presented. The effect of substitution in various parts of the molecule on β₁/β₂ selectivity and degree of partial agonism is discussed. Cardiac (β₁) selectivity is achieved by hydrophilic compounds with either p-amide substitution in the aryl ring, or a hydrogen bonding group in the amine side chain. Lipophilic compounds with branched chains tend to be β₂ selective. Partial agonist activity may also be controlled by hydrogen bonding groups in the side chain and by aromatic substitution. Here 3,4-dihydroxyl groups give full agonists, mono-and des-hydroxy (OH) groups partial agonists. The size of any o-substituent is critical and a plot of Taft's steric factor versus partial agonism gives a linear relation. By manipulation of the above factors all combinations of selectivity and agonist activity may be achieved.     

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.     

Ionic graft copolymerization. I. Homopolymerization of β-propiolactone by sodium acetate catalyst

The polymerization of β-propiolactone (βPL) by sodium acetate catalyst has been investigated. The polymerization behavior with monomer purified with calcium chloride was found to be a little different from that previously reported for this monomer. That is, poly-β-propiolactone (PβPL) obtained from βPL dried with CaCl₂ has a higher degree of polymerization than that obtained from conventionally treated βPL, and its infrared spectrum shows type II configuration, which differs from that reported in previous papers. Some chain transfer reaction is observed even for the polymerization of the CaCl₂–dried βPL; however, this is less important in toluene. The electronegativity of the anion or cation in catalyst greatly influences the rate of polymerization.