Über die Synthese von 5-Phenyl-1H-thieno[3,4—e]1,4-diazepin-2(3H)-on

The synthesis of 5-phenyl-1H-thieno[3.4—e]1.4-diazepin-2(3H)-one (16), its alkylation in position 1 and the preparation of the intermediate 3-(4-aminothienyl)-phenylketone (8) are described. In addition thieno[3.4—b]pyridin-2(1H)-one (7) is described.     

Synthesis of Polysiloxane Xerogels Using Tetraethoxysilane/(Diethylphosphatoethyl)triethoxysilane System

The xerogels, containing phosphonic acid groups ≡Si(CH₂)₂P(O)(OC₂H₅)₂ in the surface layer of their particles, are synthesized by the sol-gel method (ethanol as a solvent and fluoride ion as a catalyst). It is shown that, when 2 : 1, 3 : 1, and 4 : 1 tetraethoxysilane/(diethylphosphatoethyl)triethoxysilane ratios are used, nonporous substances are formed, whereas, at 6 : 1, 8 : 1, and 10 : 1 ratios, the xerogels with highly porous structures are produced (the specific surface area is 505–534 m²/g, the sorption pore volume is 0.34–0.53 cm³/g, and the pore diameter is 3.6–4.6 nm).     

OSW saponins: facile synthesis toward a new type of structures with potent antitumor activities

[reaction: see text] OSW saponins, featuring a 16beta,17alpha-dihydroxycholest-22-one aglycon and an acylated beta-D-xylopyranosyl-(1-->3)-alpha-L-arabinopyranosyl residue attached to the 16-hydroxyl group, have recently been discovered from a group of lily plants, which show potent antitumor activities with a novel mechanism of action. This paper describes an aldol approach to the stereoselective construction of the 16alpha,17alpha-dihydroxycholest-22-one structure from 16alpha-hydroxy-5-androsten-17-ones and propionates. Elaboration of the aldol adducts toward OSW-1, involving installation of the isoamyl ketone side chain, inversion of the 16-hydroxyl configuration, and selective protection of the C22-oxy function, has been explored and accomplished. In particular, the present route was found convenient for the synthesis of OSW saponin analogues with a C22-ester side chain. Thus, the 23-oxa-analogue of OSW-1 (40) was prepared starting from the industrial dehydroisoandrosterone (1) in a linear eight-step sequence and in 26% overall yield. Analogues with a variety of modified side chains were prepared, via aldol condensation with propionates of varying length, thiopropionate, and acetate (for preparation of 68-75) or via aminolysis of the 22,16-lactone 26 (for preparation of the 23-N-analogues). Cross metathesis (CM) reaction was also found feasible for modification at the final stage from C22-allyl ester 70. Valuable structure-activity relationships (SAR), together with the practical synthetic approach, have thus been provided to set a new stage for further studies on this new type of antitumor structures.     

Substituent Effects in S- and Se-Centered Radical Cations

The first ionization potentials of molecules XZY and 1,4-XC₆H₄ZR (X, Y are inorganic, organo- metallic, or organic substituents; Z = S, Se), as well as the energies of charge-transfer bands in the electronic spectra of tetracyanoethylene complexes of these molecules are determined by the inductive, resonance, and polarization effects of substituents X and Y. Z-Centered radical cations formed both from individual molecules in the gas phase and from those incorporated in tight radical ion pairs in solutions are closely allied in their electronic structure. The resonance parameters ⁺ _R of organosilicon, organogermanium, and organotin substituents bound to the radical cation center Z+^· were determined.     

Epoxy Composites Modified with Finely Dispersed Fillers

The thermal stability and mechanical strength of composites based on ED-20 epoxy oligomer cured with isomethyltetrahydrophthalic and methylendic anhydrides was studied as influenced by the nature and properties of finely dispersed inorganic fillers, such as carbon black, aluminum oxide, and silica nanoparticles.     

Structure and dynamics of metallomacrocycles: recognition of zinc xylyl-bicyclam by an HIV coreceptor

As platforms for the design of metal-based therapeutic and diagnostic agents, macrocycles are rigid enough to provide strong metal binding sites and orient functional groups stereoselectively, yet flexible enough to accommodate structural changes required for induced-fit recognition of biological targets. We consider the recognition of the Zn(II) complex of the bis-tetraazamacrocycle xylyl-bicyclam, a potent anti-HIV agent, by the coreceptor CXCR4, a G-protein-coupled receptor used by HIV for membrane fusion and cell entry. NMR studies show that the macrocycles of Zn(II)(2)-xylyl-bicyclam perchlorate exist in aqueous solution as two major configurations, trans-I (nitrogen chirality R,S,R,S), and trans-III (S,S,R,R). Acetate addition induced a major structural change. X-ray crystallography shows that the acetate complex contains the unusual cis-V cyclam configuration (R,R,R,R and folded) with bidentate coordination of acetate to Zn(II) plus second-coordination-sphere double H-bond formation between diagonal NH protons on the opposite cyclam face and acetate carboxylate oxygens. Detailed 1D and 2D NMR studies show that the major configuration of Zn(II)(2)-xylyl-bicyclam acetate in aqueous solution is cis-V/trans-I. Molecular modeling shows that an analogous cis-V site can be formed when Zn(II)(2)-xylyl-bicyclam binds to CXCR4, involving the carboxylate groups of Asp262 (Zn(II) coordination) and Glu288 (double H-bonding). The second cyclam can adopt the trans-I (or trans-III) configuration with Zn(II) binding to Asp171. These interactions are consistent with the known structure-activity relationships for bicyclam anti-HIV activity and receptor mutation. Consideration of the anti-HIV activity of xylyl-bicyclam complexes of other metal ions suggests that affinity for carboxylates, configurational flexibility, and kinetic factors may all play roles in receptor recognition. For example, Pd(II) cyclam complexes interact only weakly with axial ligands and are inflexible and inactive, whereas Co(III) cyclams bind carboxylates strongly, are configurationally flexible, and yet have low activity. Our findings should aid the design of new generations of active macrocycles including highly specific chemokine receptor antagonists.     

Zur Ermittlung und rechnerischen Überprüfung thermodynamischer Daten aus experimentell gefundenen Werten, 10. Mitt.: Zur Frage der Parameterzahl und Fehlerverteilung bei einigen Rechenansätzen für binäre thermodynamische Systeme

Zusammenfassung Es wird eine vergleichende Untersuchung über die Anwendungsmöglichkeit zweier dreiparametriger und zweier zweiparametriger Ansätze angestellt. Die Bestimmung der Konstanten erfolgt nach der Methode der kleinsten Quadrate, die entstehenden Fehlerquadratsummen werden als Funktion der Iterationszahl dargestellt und verglichen. Ebenso wird mit den Verbesserungen _i und den mittleren Fehlern der einzelnen Parameter verfahren. Es ergibt sich, daß der Ansatz vonWilson für stark assoziierende Systeme mit nahezu horizontaler Grenztangente die kleinste Fehlerverteilung aufweist. Die beiden dreiparametrigen Ansätze vonRedlich-Kister und vonMusil-Breitenhuber zeigen sich für das Systemn-Hexan-Methylamin besser geeignet als für die Systeme Benzol-Methanol und CCl₄-Methanol. Die Problematik der Parameterzahl wird an Hand der Fehlerverteilung bei den Ansätzen vonMB undRK aufgezeigt und diskutiert.Das Programm wurde in der Programmiersprache FORTRAN erstellt und mit der UNIVAC-490-Computer-Anlage des Grazer Rechenzentrums gerechnet.

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Four thermodynamical statements are tested with regard to their applicability to binary systems, two statements having three and two only two parameters. The least square method ofGauss shows that theWilson statement has the smallest dispersion of errors for systems with nearby horizontal boundary tangent. [vv], _i and are shown as functions of the number of iterations. The problem of the parameters' number is shown and discussed by means of the dispersion of errors for theMusil-Breitenhuber (MB) andRedlich-Kister (RK)-statements.The programme is written in FORTRAN and has been used the UNIVAC-490-Computer of the Graz Computer Centre.

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Mit 5 Abbildungen

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Herrn Professor Dr.Robert Fischer zum 65. Geburtstag in Dankbarkeit und Verehrung gewidmet.

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bis 6. Mitt.:F. Gölles, Mh. Chem.92, 981 (1961);93, 191, 201 (1962);94, 1108 (1963);95, 1656 (1964);96, 1366 (1965);7. bis 9. Mitt.:F. Gölles undA. Höpfner, Mh. Chem.97, 368, 911 (1966);99, 230 (1968).     

Nucleophilic reactions of polydialkylcyclosilazanes

A study is made of the catalytic condensation polymerization of polydialkylcyclosilazanes [RR'SiNH]_n (n=3,4; R=CH₃, C₂H₅; R'=C₂H₅, C₄H₉, C₆H₁₃, C₉H₁₉) in the presence of small amounts of nucleophilic reagents, to give compounds of the general type R₅R₆'Si₆N₃(NH)₂ and oligomers. The reactivities of polydialkylsilazanes decrease with increase in aliphatic group chain length.     

Polyazoxyfurazans in reactions with ammonia

The reaction of 4,4"-bis(4-nitrofurazan-3-yl-NNO-azoxy)azoxyfurazan with ammonia affords a product of nucleophilic substitution for the furazanyldiazene oxide fragment, while the nitro groups remain intact.     

Production of recombinant bleaching enzymes from thermophilic microorganisms in fungal hosts

Cost-effective production of enzymes for industrial processes makes the appropriate selection of the host-vector expression system critical. We have developed two systems for the bulk production of bleaching enzymes from thermophiles. Kluyveromyces lactis has been developed as a secretion host employing expression vectors based on the 2μ-like plasmid pKD1 of Kluyveromyces drosophilarium. Our second system involves the filamentous fungus Trichoderma reesei. Fusion and nonfusion vectors have been constructed using the strong cellobiohydrolase 1 (cbh1) promoter. The KEX2 protease cleavage site and a 6 × HIS-tag have been incorporated to facilitate both cleavage and purification of the mature foreign proteins.