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 .     

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.     

Heterocyclisierungen an Ascorbinsäuren mit α, ß- ungesättigten Aldehyden und Ketonen, 2.Mitt.: Michael-Reaktionen von Ascorbinsäuren mit Acroleinderivatenstrukturelle und physikochemische Beobachtungen

Heterocyclisations of Ascorbic Acids with α, β-Unsaturated Aldehydes and Ketones, II: Michael Reactions of Ascorbic Acids with Acrolein Derivatives - Structural and Physicochemical Behaviour. The Michael reaction of ascorbic acids ( la – d ) with acrolein ( 2 ) and some derivatives ( 7 , 8 ) is reported. The pH-optimum of the reaction course is 4. Furthermore, solvents supporting ionisation are favourable. α- and β-subsituted acrolein derivatives react differently: Crotonaldehyde, a β-substituted derivative, reacts nearly quantitatively to the spiro compounds 3e and 3f , whereas α-ethyl-acrolein favours the formation of 4g and 4h .     

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 .     

Neue Reaktionen an Phthalidisochinolinalkaloiden. Alkoxytauschreaktionen und Isomerisierungen an α- und β-Narcotin

New Reactions of Phthalidoisoquinoline Alkaloids. Alkoxy Exchange Reactions and Isomerisations of α- and β-Narcotine Substitution of the 7-methoxy group in α- and β-narcotine by other alkoxy groups occurs in an anhydrous ROH/RONa system. It is accompanied by isomerisation in position 3 with preference for the α-configuration (5R, 3S). In an alkaline aqueous system (ROH/KOH or 1N KOH only isomerisation in position 3 with preference for the β-configuration (5R, 3R) was observed. Some of the new 7-alkoxynarcotines were evaluated for their antitussive activity.     

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.     

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 ).     

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.     

Die Kondensation von γ-und δ-Oxo-carbonsäureester mit 1,2-, 1,3- und 1,4-Alkylendiaminen

Condensation of Esters of γ- and δ-Oxocarboxylic Acids with Alkylene-1,2,1,3- and 1,4-diamines. Esters of γ-and δ-Oxocarboxylic acids condense with alkylene-1,2-, 1,3-, and 1,4-diamines and yield bicyclic lactams (5) . The path of the reaction was studied by spectroscopic methods using ethyl levulinate and N-methyl-propylene-1,2-diamine. The first step is the formation of an “aminalester” by reaction of the CO-group of ethyl levulinate with alkylene diamine, followed by intramolecular ring closure.     

Thion- und Dithioester, 48. Mitt. α,β-Ungesättigte Thioester in Diels-Alder-Reaktionen und Michael-Additionen

Thiono and Dithio Esters, XLVIII: α,β-Unsaturated Thio Esters in Diels-Alder Reactions and Michael Additions The reaction of cinnamic acid thio esters with different dienophiles leads to the formation of the Diels-Alder products 3 – 8 ; with lithium enolates the Michael adducts 11 and 13 were isolated.     

Über das Polymorphie-Verhalten von 7-(β-Hydroxypropyl)- und 7-(β,γ-Dihydroxypropyl)-theophyllin

On the Polymorphism of 7-(β-Hydroxypropyl)-and 7-(β,γ-Dihydroxypropyl)-theophylline The polymorphism of 7-(β-hydroxypropyl)- and 7-(β,γ-dihydroxypropyl)-theophylline was studied with differential scanning calorimetry and thermomicroscopy. Crystallization in vitreous supercooled melts yields polymorphic modifications. Their formation and transformation with time was studied.     

Δ2-1,2,4-Oxadiazoline durch Kondensation von Amidoximen mit Ketonen und Aldehyden

Δ²-1,2,4-Oxadiazolines by Condensation of Amidoximes with Ketones and Aldehydes Using acetic acid as a solvent, ketones and aromatic aldehydes react with amidoximes 1 to cyclic products, Δ²-1,2,4-oxadiazolines 3 . The lack of reactivity in neutral milieu is explained by MNDO calculations. Protonated carbonyl compounds are discussed to be the reactive species.     

Conformational investigation of α,β-dehydropeptides

Conformations of three series of model peptides: homochiral Ac-Pro-L-Xaa-NHCH₃ and heterochiral Ac-Pro-D-Xaa-NHCH₃ (Xaa=Phe, Val, Leu. Abu. Ala) as ivell as α,β-dehydro Ac-Pro-ΔXaa-NHCH_s [ΔXaa = (Z)-ΔPhe, ΔVal. (Z)-ΔLeu, (Z)-ΔAbu] were investigated by CD spectroscopy in 2 % dichloromethanecyclohexane, trifluoroethanol. water. and occasionally in other solvents. The spectra of homochiral peptides show a significant solvent dependence. Folded structures are present in 2% dichloromethane-cyclohexane and unordered ones occur in water. The folded conformers are of the inverse γ-turn type for all the peptides but Ac-Pro-L-Phe-NHCH₃ for which the type-I β-turn is preferred. The changes in the spectra of the heterochiral peptides are limited. The compounds adopt the typc-II β–turn in 2% dichloromethanecyclohexane, represented by class B spectra, and retain this conformation in water as well as in fluorinated alcohols but not always to a full extent. The CD spectra of the unsaturated peptides in 2%, dichloromethanecyclohexane, although they cannot be assigned to any common spectral class, must be attributed to the βII-turn conformation as determined for these coinpounds by NMR and IR spectroscopy. The CD spectra of dehydropeptides exhibit a considerable solvent dependence and suggest unordered structures in water.     

Conformational investigation of α, β-dehydropeptides

The crystal structure of Ac-Pro-ΔVal-NHCH₃ was examined to determine the influence of the α,β-dehydrovaline residue on the nature of peptide conformation. The peptide crystallizes from methanol-diethyl ether solution at 4° in needle-shaped form in orthorhombic space group P2₁2₁2₁ with a= 11.384(2) Å, b = 13.277(2) Å, c = 9.942(1) Å. V = 1502.7(4) ų Z = 4, D_m= 1.17 g cm^?3 and D_c=1.18 g cm^?3 The structure was solved by direct methods using SHELXS-86 and refined to an R value of 0.057 for 1922 observed reflections. The peptide is found to adopt a β-bend between the type I and the type III conformation with φ₁=?68.3(4)°, ψ₁=? 20.1(4)°, φ₂=?73.5(4)°= and Ψ₂=?14.1(4)°=. An intramolecular hydrogen bond between the carbonyl oxygen of ith residue and the NH of (i+ 3)th residue stabilizes the β-bend. An additional intermolecular N.,.O hydrogen bond joins molecules into infinite chains. In the literature described crystal structures of peptides having a single α,β-dehydroamino acid residue in the (i+ 2) position and forming a β-bend reveal a type II conformation.     

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.