Nitroketenaminale, 9. Mitt.: Zur Umsetzung von α,β-ungesättigten Aldehyden mit Nitroketenaminalen

Nitroketeneaminals, IX: Reaction of α,β-Unsaturated Aldehydes with Nitroketeneaminals Reaction of α,β-unsaturated aldehydes 1a , b with nitroketeneaminal 2a in boiling acetic acid leads to 2-amino-3-nitropyridines 4 unsubstituted at C-6. By refluxing 1a and 2a in alcohol/acetic acid or in alcohols, respectively, 2-alkoxy-1,2,3,4-tetrahydropyridines 7a and 8a are obtained. The reaction of 1a and 2b yields 5-alkoxy-2,3,4,5,6,7-hexahydroimidazo[1,2-a]pyridines 7b and 8b . By ¹H-NMR spectroscopy the relative configuration of 7aC, 7aT, 7bC , and 7bT can be determined.     

Massenspektrometrische Untersuchungen an isomeren α,β- und β, γ-ungesättigten Ketonen mit raumerfüllenden Substituenten

A Mass Spectrometric Study on Isomeric α,β- and β,γ-Unsaturated Ketones with Bulky Substituents The mass spectra of the α,β- and β,γ-unsaturated ketones 1-4 (scheme 1) are very different depending on the stereochemistry of the double bond. The E-configurated ketone 2 predominantly shows McLafferty fragmentation, whereas Z-configurated ketone 1 reveals ?-cleavage. In the β, γ-unsaturated ketones 3 and 4, mainly loss of the pertinent allyl radical by α-cleavage was observed.     

Reaktionen α,β-ungesättigter γ-Oxosulfone mit Nucleophilen

Reactions of α,β-Unsaturated γ-Oxosulfones with Nucleophiles Bromination of the γ-oxosulfones 1 and subsequent dehydrohalogenation leads to the α,β-unsaturated γ-oxosulfones 3 . These products react with primary and secondary amines to yield the enaminoketones 7 . γ-Oxobissulfones 10 are formed from 3 by addition of the sulfinic acids 9 . Thioles 11 react with 3 to give the γ-oxomercaptosulfones 12 or the thioacetals 14 .     

Synthese von γ,γ'-Dihydroxysulfonen und γ-Hydroxy-γ'-ketosulfonen

Syntheses of γ,γ'-Dihydroxysulfones and γ-Hydroxy-γ'-ketosulfones Reduction of γ,γ'-diketosulfones 1 with dimethylaminoborane leads to γ,γ'-dihydroxysulfones 3 via γ-hydroxy-γ'-ketosulfones 2 . The influence of substituents on the ratio of the yields of 2 and 3 is investigated.     

Synthese von α-Trihalogenmethyl-γ-oxosulfonen

Synthesis of β-Trihalogenomethyl-γ-oxosulfones The title-compounds 6 are formed by reaction of sulfinic acids 4 with 1,1,1-trihalogen-2-buten-4-ones 1 and 1,1,1-trihalogen-2-chloro-4-butanones 8 , respectively, or by addition of thioles 3 to 1 and subsequent oxidation.     

Über Dialkyl-[β,β,β-trichlor-bzw. β,β,β-triphenyl-äthyl]-amine. 34. Mitt. über α-halogenierte Amine

Dialkyl-[β,β,β-trichloro- or β,β,β-triphenyl-ethyl]-amines Reactions of α-halo amines 2 with trichloromethyllithium give dialkyl-[β,β,β-triphenyl-ethyl]-amines 1 , with triphenylmethyllithium dialkyl-[β,β,β-triphenyl-ethyl]-amines 3 .     

Analysis of γβ, βγ, γγ, ββ multiple turns in proteins

Abstract: The number of γ‐turns in a representative protein dataset selected from the current Protein Data Bank has increased almost seven times during the past decade. Eighty percent classic γ‐turns and 57% inverse γ‐turns are associated as multiple turns with either another γ‐turn or a β‐turn. We refer to these as multiple turns of the (γβ)_1,2,3 or (βγ)_1,2,3 type, depending upon whether the γ‐turn is before or after the β‐turn along the protein chain, respectively. However, for multiple turns involving only γ‐turns, we follow the nomenclature analogous to that proposed earlier for the multiple (or double) β‐turns. Fifty‐eight per cent β‐turns are associated as multiple turns with another β‐turn. We extracted multiple turns from the protein dataset and classified them on the basis of individual γ‐ or β‐turn types and the number of overlapping residues. Furthermore, we evaluated the amino acid positional potentials and determined the statistically significant amino acid preferences, hydrogen bond/side‐chain interaction preferences in the multiple turns and secondary structure preferences for residues immediately flanking these turns. The results of our analysis would be useful in the modeling, prediction or design of multiple turns in proteins. The amino acid sequence corresponding to the multiple turn, position in the protein chain, PDB Code/chain in which multiple turn is present and the individual turn types constituting the multiple turns are available from our website and this information would also be integrated in our Database of Structural Motifs in Proteins ( http://www.cdfd.org.in/dsmp.html ).     

Analysis of γβ, βγ, γγ, ββ continuous turns in proteins

Abstract: We report the observation of continuous turns in proteins which comprise individual γ‐turns or β‐turns or both that are situated immediately one after the other along the polypeptide chain. The continuous turns were identified from a representative data set of three‐dimensional protein crystal structures. The γβ/βγ, γγ and ββ continuous turns represent peptides of varying amino acid residue lengths and conformations. The continuous turns frequently observed in proteins were: γβ, between a coil and a strand; βγ, between a helix and a strand; γγ, between coils; and ββ, either between a strand and a coil or between strands or coils. We determined the statistically significant amino acid residue preferences at individual positions in the turn, calculated amino acid positional potentials and analyzed main chain hydrogen bonds and side‐chain interactions likely to stabilize the continuous turns. The data on continuous turns have been integrated in the database of structural motifs in proteins (DSMP) on our web server at ( http://www.cdfd.org.in/dsmp.html ). This is useful to make queries on sequences compatible with different continuous turns.     

Eine dreistufige Synthese der δ-Aminolaevulinsäure

A Three-Step Synthesis of δ-Aminolaevulinic Acid Piperidine-2,5-dione (4) is prepared by catalytic hydrogenation of 5-hydroxy-2-pyridone (3) . Ring opening of the lactam 4 with concentrated hydrochloric acid yields the hydrochloride of δ-aminolaevulinic acid (2) .     

Die Synthese von β-Phenyl-isoserinen durch Ammonolyse von β-Phenylglycidestern,II

Synthesis of β-Phenyl-isoserines by Ammonolysis of β-Phenylglycidates, II Ammonolysis of the β-phenylglycidates 1a–e yields the erythro-isoserine-amides 2a–e , from which the acids 3a–e can be obtained by hydrolysis. 1a with benzylamine also gives the isoserine derivative 8 . On the other hand, treatment of 1a with piperidine affords the serine-compound 6 . The structures are confirmed by the NMR-spectra and by comparison with the corresponding serines 4a–e .     

Synthese von 3-methylenmonosubstituierten 2-Oxo-tetrahydrofuranen durch Umsetzung von α-Keto-γ-lactonen mit Wittig-Reagenzien

Synthesis of 3-Methylenetetrahydrofuran-2-ones from α-Keto-γ-lactones with Wittig Reagents The synthesis of the 3-methylenetetrahydrofuran-2-ones 3a--q from the α-keto-γ-lactones 1a,b and the Wittig compounds 2a--h is described.     

α-Thiotetronsäuren, 1. Mitt.: Synthese und Eigenschaften von γ-Alkyliden-α-thiotetronsäuren

α-Thiotetronic Acids, I: Synthesis and Properties of γ-Alkylidene α-Thiotetronic Acids We report on the synthesis of the alkylidene α-thiotetronic acids 11 and 12a and a variety of their derivatives, starting with 2,3-dimethoxysuccinic thioanhydride ( 4 ) or diethyl 3-thioxoglutarate. The rhodium(II)-catalysed decomposition of the diazoketone 26 furnishes the reductone 12p and the aminoreductone 12r with the thietanone 27 as one of the by-products.     

Microwave‐accelerated synthesis of psychoactive deuterated N,N‐dialkylated‐[α,α,β,β‐d4]‐tryptamines

A large number of N,N‐dialkylated tryptamines are known to induce psychoactive effects in humans. This has resulted in their increased attention within clinical and forensic communities. Deuterated tryptamines are ideal for use as internal standards during MS bioanalysis or of use in biochemical NMR studies. The present study reports on a microwave‐enhanced synthesis of 22 N,N‐dialkylated‐[α,α,β,β‐d4]‐tryptamines via the reduction with lithium aluminium deuteride of glyoxalylamide precursors obtained by the procedure of Speeter and Anthony. Syntheses were carried out using a single‐mode system under elevated pressure conditions where anhydrous tetrahydrofuran was used as the solvent at 150°C. Good yields were obtained within 5 min. Copyright © 2008 John Wiley & Sons, Ltd.     

Stereochemie der Reformatsky-Reaktion von 2-Alkylcyclohexanonen mit α-Brommethylacrylsäureethylester

Stereochemistry of the Reformatsky Reaction of 2-Alkylcyclohexanones with Ethyl α-(Bromomethyl)acrylate A relation between the chemical shifts of the ¹³C-NMR signals of the carbon atoms 4, 5 and 9 and the conformation of the lactone oxygen was found for spiro-α-methylene-γ-butyrolactones prepared by the Reformatsky reaction of 2-alkylcyclohexanones with ethyl α-(bromomethyl)acrylate. It was confirmed by CD measurements on the pyrazoline derivative of one of the lactones. From the structures of the reaction products it was deduced, that trans addition (relative to the substituent at position 2) of the organometallic reagent is prefered.     

Properties of a Resiniferatoxin-stimulated,Calcium Inhibited but Phosphatidylserine-dependent Kinase,which is Distinct from Protein Kinase C Isotypes α, β1γ, δ, ε and η

We have separated a resiniferatoxin-stimulated histone-kinase activity from human neutrophils, elicited mouse macrophages and murine alveolar macrophages by hydroxyapatite chromatography. The assay conditions for resiniferatoxin kinase were optimized as part of this study and in the presence of phosphatidylserine but absence of Ca²⁺ the K_a for histone IIIs phosphorylation by resiniferatoxin was calculated as 16 nm . Using a phosphate gradient of 20–500 mm , peaks of protein kinase C activity could be washed from the hydroxyapatite column in 300 nm phosphate and resiniferatoxin kinase recovered in 500 mm phosphate. At the optimum concentration of 160 nm , the ability of resiniferatoxin to induce enzyme activity was compared with a range of phorbol esters all at the same concentration. These related compounds failed to activate resiniferatoxin kinase although they have previously been shown to activate protein kinase C isotypes. Similarly sn-1,2,-dioleoylglycerol and the potent irritant capsaicin at 30 μm failed to activate the kinase. A Scatchard analysis of [³H] phorbol dibutyrate binding produced a linear plot (K_d 41·6 nm ; B_max 11·6 fmol unit^?1) and binding was inhibited by resiniferatoxin and 12-O-tetradecanoylphorbol-13-acetate (TPA), with resiniferatoxin 700 times more potent than TPA in this respect. A radiolabeled resiniferatoxin binding assay was also used to demonstrate specific binding of [³H]resiniferatoxin which could be inhibited by unlabelled compound. Resiniferatoxin kinase activity was shown to be distinct from the protein kinase C isotypes α, β₁, γ δ and ε by means of immunological analysis and from the η isotype, because that isotype was not stimulated by resiniferatoxin but was stimulated by TPA when a pseudosubstrate was used. In addition the resiniferatoxin-stimulated activity was inhibited in-vitro by the addition of Ca²⁺ (K_i 0·1-0·5 nm free Ca²⁺). Further purification of resiniferatoxin kinase by Superose chromatography indicated a major activity fraction of about 70–90 kDa. Thus resiniferatoxin kinase, isolated from human and mouse inflammatory cells is distinct from the known isotypes of protein kinase C and is a major resiniferatoxin receptor.