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Despite their importance as members of the Roundabout (Robo) family in the control of axonal and vascular patterning, the transcriptional regulation of these genes is poorly understood. In this study, we show that members of the Sry-related high mobility box (Sox) transcription factor family as being transcriptional regulators of roundabout4 (robo4), a Robo gene family member that participates in sprouting angiogenesis in vivo, in zebrafish. Double whole mount in situ hybridization analysis in zebrafish embryos revealed co-localization of the vascular relevant Sox factors sox7 or sox18 mRNA with robo4 transcripts in developing intersomitic vessels. A 3-kb human ROBO4 promoter element was able to drive reporter expression in zebrafish to recapitulate the endogenous temporal intersomitic vessel expression pattern of robo4. EMSA analysis confirmed binding of Sox18 to a canonical Sox binding site (from -1170 bp to -1176 bp) in the ROBO4 promoter (3 kb), and mutation analysis indicated that this site was partially responsible for ROBO4 promoter activity in ECs. A combination of gain- and loss-of-function analysis identified Sox7 and Sox18 co-regulation of robo4 but not fli1a transcripts in zebrafish. Finally, Sox-mediated robo4 transcriptional regulation is conserved across evolution. These studies imply Sox-mediated transcriptional regulation of Robo4 in the developing embryonic vasculature.

Configurationally unstable biaryl lactones of type (M)-1 ⇌ (P)-1 and ring-opened 2-acyl-2‘-hydroxy biaryl compounds of type (M)-4 ⇌ (P)-4 are versatile precursors for the atroposelective preparation of axially chiral biaryls. The activation barriers of their atropisomerization process, which constitutes a fundamental precondition for the dynamic kinetic resolution, were determined by dynamic NMR spectroscopy for rapid processes and by HPLC-monitored racemization of enantiomerically enriched material for smaller interconversion rates. For the lactones, the free activation energies ΔG⧧298 increase with the steric demand of the substituent R ortho to the biaryl axis in the series H < OMe (t1/2 ≈ ms) < Me (t1/2 ≈ s) < Et < i-Pr (t1/2 ≈ min) < t-Bu (t1/2 ≈ d). The formally ring-opened 2-acyl-2‘-hydroxy biaryls, which interconvert via the lactol isomers 5 as the cyclic (and thus configurationally less stable) intermediates, have a significantly slower atropisomerization rate as a result of the high loss in acti...

The substitution-labile thiophene complex [CpRu{(S,S)-CHIRAPHOS}(SC4H4)]BF4 (2) [(S,S)-CHIRAPHOS = (2S,3S)bis(diphenylphosphanyl)butane], prepared from [CpRu{(S,S)-CHIRAPHOS}Cl] (1), thiophene, and AgBF4, reacted with the biaryl-thionolactones 3a–f to give the corresponding S-coordinated complexes 4a–f in high yields. The structure of 4c, which crystallized as the pure (S,S,P) diastereoisomer, was determined by X-ray crystallography. Coordination of the ruthenium fragment caused an elongation of the C=S bond, a contraction of the C–O bond within the lactone ring and a flattening of that ring. Single hydride transfer with LiBEt3H converted 4a–f into the thiolactolate complexes 5a–f in good yields and diastereoselectivities. An X-ray structure determination of the major isomer of 5a revealed it to be the (S,S,S,P) diastereoisomer. Protonation with NH4PF6 converted 5a–f into the corresponding ring-opened thioaldehyde complexes 6a–f. Alkylation of 5a with methyl iodide resulted in Ru–S cleavage to give the oxothioacetal 7a and [CpRu{(S,S)-CHIRAPHOS}I] (8). Full reduction of 4a–f with LiAlH4 produced the thiolate complexes 9a–f in high yields and 6–74% de. Methylation at sulfur converted 9a–c into the corresponding thioether complexes 10a–c, which were cleaved to 8 and the free methyl thioethers 11a–c without isomerization of the biaryl axis.

From the rare West African liana, Dioncophyllum thollonii (Dioncophyllaceae), the known acetogenic tetralones, cis - and trans -isoshinanolone, were isolated. Exemplarily on this material, a new ruthenium-catalyzed oxidative degradation procedure, related to the well-established stereoanalysis of 1,3-dimethyltetrahydroisoquinolines, was elaborated. The method allows to unambiguously attribute the absolute configuration of these natural products, which likewise occur in several other plant species. For the rapid discrimination between the four possible stereoisomeric forms of isoshinanolone (i.e. the cis - and trans -diastereomers and their enantiomers), an HPLC-analytical procedure on a chiral stationary phase has been developed.

Exemplarily for a root extract of the West African liana Dioncophyllum thollonii a strategy for the rapid identification of secondary metabolites in plant extracts is presented, based upon on-line coupling of high-performance liquid chromatography with nuclear magnetic resonance detection. For a first overview, an on-flow experiment was performed, which allowed the identification of the naphthylisoquinoline alkaloid dioncophylline A. A second alkaloid, 5′-O-demethyldioncophylline A, was identified by subsequent application of stop-flow two-dimensional HPLC–NMR ROESY experiments. In the case of coeluting compounds, the design of appropriate time-slice experiments allowed the characterization of the diastereomeric tetralones trans- and cis-isoshinanolone. Thus, through consequent use of all different experimental modes available in HPLC–NMR, a phytochemical screening of plant extracts can be realized in a fast and reliable way. The NMR detection allows the characterization of diastereomeric compounds even in the case of far-reaching chromatographic coelution.

The synthesis of a variety of differently substituted 1,2,3,4-tetrahydroquinolines by a new three-component reaction involving an imine (Ar-NCHR), an α-branched and enolizable aldehyde (R 1 R 2 CHCHO), and a nucleophile (ROH, ArSH, ArNH 2 , H 2 O) is described. The in situ generation of the imine (that allows a four-component process), and the reactions of an enantiomerically pure imine and/or aldehyde were also studied. A short discussion of the reaction mechanism is reported.

The title compound 2c, a potentially useful synthetic intermediate in stereoselective biaryl synthesis, has been prepared from the oxolactone 1c, by treatment with Lawesson′s reagent. An X-ray structure analysis reveals its strongly helically distorted structure, the overall molecular distortion even slightly exceeding that of the corresponding oxo compound 1c.

The elucidation of the absolute configuration of a lactone-bridged biaryl was performed by multiple scattering X-ray experiments. This helical, but configuratively unstable compound shows spontaneous deracemization by crystallization. For the rapid stereochemical correlation with the examined crystal, an analytical device was developed, by chromatography on a chiral HPLC phase.

The preparation of the thiobutyrolactone complexes [Cp(dppx)Ru-1]PF 6 with dppx = dppm ( 1a ) and dppe ( 1b ) is described. Raman spectra of the polycrystalline solids and the CH 2 C1 2 solutions were recorded by means of the scanning multichannel technique and charge-coupled device detection. The results are reported with complementary IR data. Vibrational assignments are proposed for the compounds and the carbon-sulfur stretching vibrations have been assigned by means of polarized Raman measurements. Likewise, spectra of thiono-benzonaphthopyranones 2–4 and their complexes were recorded. Assignments are given for the lactones themselves and their ruthenium complexes.

Semiempirical and ab initio calculations on the binding properties of the AlCl3 complex of 1,3-dimethylbenzo [b][naphtho[1,2-d]pyran-6-one are reported. Compounds of this type are key intermediates in the stereoselective synthesis of axially chiral biaryl systems. Semiempirical (MNDO, PM3) and ab initio (STO-3G, 3-21G) calculations give important information about conformational changes that occur by complexing the free lactone with AlCl3: the calculations predict a significant influence on the lengths of the (CO)exo and (CO)endo bonds, and a distinct planarization of the heterocyclic lactone part of the complexed benzonaphthopyranone. IR and Raman spectroscopy was applied in order to confirm the theoretical predictions. The good agreement of results obtained by semiempirical frequency calculations with the experimental data supports the assignment of vibrational bands affected on coordination. The highest shift caused by coordination (−152 cm−1) is observed for v(CO).

The adduct formed between CpZrCl3 and a biaryl lactone has been studied in toluene solution by Zr K X-ray absorption spectroscopy. The adduct is dimeric in toluene, as evidenced by a long Zr-Zr distance of 3.76 A. In the dimer [CpZrCl2(lactone 1d)(μ-Cl)]2, each zirconium centre is pseudo-octahedrally coordinated with the lactone carbonyl oxygen coordinated to the metal at a distance of 2.14 A.

The preparations of novel thionolactone-bridged configuratively labile biaryls and their [Cp(R3P)2Ru]+-complexes are described. The dynamics of helimerization of these complexes and their reactivity towards nucleophiles have been investigated. Hydride transfer reagents lead to a cleavage of the thionolactone bridge to give the corresponding thiolate complexes, apparently via intermediate exothiolactolate ruthenium complexes. A similar lactolate analog is formed upon addition of a mild S-nucleophile.

A rational synthesis of the biaryl lactone 3 is described. This bridged biaryl, which gradually helimerizes at room temperature, could be synthesized in a non-racemic form, chemically by atropo-selective ring opening with a chiral O-nucleophile and subsequent ring closure, and chromatographically by HPLC on a chiral phase. For the enantiomerization process (M)-3 ⇄ (P)-3, the activation parameters were determined.

Transition-metal-substituted phosphorus ylides M(NtBu)2(CHPPh3Cl, with M  Mo, W, have been shown to be useful C-nucleophiles for the selective CO bond cleavage of benzocoumarin-type “axially prostereogenic” biaryl lactones. The reaction of the metallo-ylide with the lactone leads to an eight-membered metallacycle as established by spectroscopic data and confirmed by an X-ray diffraction study of one of the products.

A series of silylketene thioacetals derived from 2-pyridylthioesters have been prepared and the (E) (Z) configuration of some of them has been determined by NMR spectroscopy. In the presence of Lewis acids these compounds stereoselectively react with imines to afford β-lactams in a convenient one-pot procedure. An enantioselective β-lactam synthesis promoted by a chiral Lewis acid is also described.

The synthesis of a variety of differently substituted 1,2,3,4-tetrahydroquinolines by a new three-component reaction involving an imine (Ar-NCHR), an α-branched and enolizable aldehyde (R 1 R 2 CHCHO), and a nucleophile (ROH, ArSH, ArNH 2 , H 2 O) is described. The in situ generation of the imine (that allows a four-component process), and the reactions of an enantiomerically pure imine and/or aldehyde were also studied. A short discussion of the reaction mechanism is reported.

The preparation is reported of the first series of (racemic) chiral rhenium complexes with “axially prostereogenic” biaryl lactone ligands, which a

A simple two-step synthesis of a series of ether-type bridged biaryls 3, as favorable models for studies of helimerization processes, is described. Starting from the known corresponding lactones 1, a variety of differently substituted representatives 3 is prepared, greatly varying by the degree of steric hindrance and thus molecular distortion. NMR spectroscopy and especially X-ray diffraction reveal the ethers 3 to be helically distorted, depending on the size of the ortho substituents R.

The title biaryl was prepared by Pd-catalyzed intramolecular aryl coupling. It crystallizes monoclinically in the space group P21 with a = 1064.9(2), b = 1850.6(5), c = 742.5(1) pm and β = 106.06(2)°. The asymmetric unit contains two molecules together with one phenol.

The title compound was prepared from the cor­responding “ordinary” oxolactone bridged biaryl using Lawesson’s reagent. It crystallizes from dichloromethane / petroleum ether in the mono­clinic system, space group P21/a; a = 1115.7(2),b = 1383.9(2), c = 1042.0(1) pm and β = 106.67(1)°.

The title compound was obtained as an unexpected by-product in the attempted biaryl coupling of phenyl 1-methoxy-2-naphthoate with 2-methoxy-1-naphthyl magnesium bromide. From ether/petroleum ether it crystallizes from the purified reaction mixture as colorless plates of the space group P21/a; a = 1258.7(5) pm, b = 1791.1(8) pm, c = 583.8(2) pm, and β = 93.68(3)°. The most characteristic feature of the structure is an intramolecular hydrogen bond quasi forming a fourth 6-membered nearly planar ring system.

The title compound was prepared by intramolecular aryl coupling of the corresponding phenyl bromonaphthoate. It crystallizes from CH2Cl2/petroleum ether in the orthorhombic system, space group P212121, with a = 1021.3(1) pm, b = 1616.3(2) pm, c = 968.9(1)pm.

The title compound was prepared from the corresponding alcohol, by hydroxy/halogen exchange reaction. It crystallizes from petroleum ether in the orthorhombic system, space group Pbcn, with a = 2830.1(6) pm, b = 821.7(2) pm, c = 1444.2(4) pm.

Die fortschreitende Entwicklung der Fernmeldetechnik zu immer hoheren Frequenzen stellt an die Isolierstoffe Anforderungen, wie sie im gleichen Mase in der Niederfrequenz- oder Starkstromtechnik nicht notig sind. Insbesondere sind es die dielektrischen Verluste, welche die Verwendungsfahigkeit des einen oder anderen Dielektrikums im Kabel-, Kondensatoren- oder Apparatebau masgebend beeinflussen, wo es darauf ankommt, die Dampfung moglichst gering zu halten. Andererseits macht man sich gerade die Hohe der dielektrischen Verluste bzw. die durch sie hervorgerufene Erwarmung technisch zunutze, indem man z B. Papiere, Holzer u. dgl. im Hochfrequenzfeld eines Kondensators trocknet. Ihre groste Bedeutung hat diese Technik heute in der dielektrischen Erwarmung des menschlichen Korpers, der sogenannten Kurzwellentherapie, gefunden. Aber noch von einer dritten Seite, namlich der des Chemikers, beginnt man den dielektrischen V erlusten steigende Aufmerksamkeit zu schenken, um mit ihrer Hilfe Aufschlusse uber den Bau von Molekeln bzw. den Ablauf chemischer Reaktionen zu erhalten. Hier stehen wir zwar in den ersten Anfangen einer Entwicklung, und die bisherigen Ergebnisse lassen noch nicht erkennen, wie weit sich hieran berechtigte Hoffnungen knupfen lassen, doch zeigen die zahlreichen Veroffentlichungen der letzten Zeit, welch groses Interesse man diesem Problem entgegenbringt.