Bibliothek

Notizen: The complexes of the three BrCN-cleaved fragments of sperm whale apomyoglobin with hemin were studied by circular dichroism (CD). In native myoglobin, the heme is located in the middle fragment; the isolated peptide (residues 56-131), however, produces little extrinsic Cotton effects by the addition of hemin, although about four molecules of hemin are bound to this peptide. In marked contrast, the COOH-terminal peptide (residues 132-153), which binds three hemin molecules, shows strong Cotton effects in the Soret bands and drastically changes its conformation from unordered to highly helical. The Arg-modified or Lys-deaminated peptide no longer undergoes conformational changes by the addition of hemin, suggesting that the two propionic acid groups of one hemin molecule interact with the Arg residue and one of the Lys residues, which stabilizes the induced helical conformation. The NH2-terminal peptide (residues 1-55) binds one hemin molecules, and the helicity of this fragment is slightly enhanced by the addition of hemin. Both the CD and difference absorption spectra indicate that the mode of interaction between the peptides and hemin are different for the three apomyoglobin fragments.

Notizen: CD study of four modified nucleosides, constituents of tRNA molecules, revealed that 2-thio-5-methyluridine and 5-methyluridine in aqueous solution, 0.1N HCl, and organic solvents essentially occur in an anti-conformation. 5-Methylcytidine also occurs in an anti-conformation similar to cytidine in aqueous solution and organic solvents, while 2-thiocytidine dihydrate appears to occur in an anti-conformation. It is stressed that the CD data of thionucleosides might be applied to the successfully conformational analysis of tRNA molecules.

Notizen: It has been inferred from previous studies that Mn2+ ions bind preferentially to G·C base pairs in DNA, and it has even been suggested that this preference for G·C pairs might be responsible for some of the Mn2+ specific effects observed in various biochemical reactions. In this paper we investigate the AT/GC preference of Mn2+ by direct competition studies in which AT-rich DNA was dialyzed against GC-rich DNA in the presence of varying amounts of Mn2+. Analysis of these results demonstrates that over a wide range of Mn2+/DNA(P) molar ratios, Mn2+ binds to A·T and to G·C base pairs with virtually identical affinity, although in a somewhat different mode. Both the present and previous nmr, uv, CD, and melting studies are discussed in terms of the different modes of binding of Mn2+ to single- and double-stranded DNA.

Notizen: We have determined extinction angles and flow birefringence of T7 bacteriophage DNA over a wide range of shear, polymer concentration, and solvent ionic strength. From these data, information on the simple salt dependence of coil permeability to solvent and on short-range intrachain interactions (persistence length) was obtained. At all ionic strengths, our results are consistent with a partially draining coil in the Gaussian subchain dynamical theory of Rouse-Zimm-Tschoegl-Bloomfield. Salt dependence of persistence length is comparable to, although somewhat less than, that obtained previously using similar methods with a fivefold higher-molecular-weight DNA (T2 bacteriophage DNA). Possible reasons for observed discrepancies are analyzed, and the results of this work are compared in detail to other current studies of solvent ionic strength dependence in persistence length and hydrodynamic properties of DNA.

Notizen: Variation of collagen fibril structure in tendon was investigated by x-ray diffraction. Anatomically distinct tendons from single species, as well as tendons from different species, were examined to determine the variations that exist in both the axial and lateral structure of the collagen fibrils. The meridional diffraction is derived from the axial collagen fibril structure. Anatomically distinct tendons of a particular species give meridional patterns that are indistinguishable within experimental error. The meridional diffraction patterns from tendons of different mammals are similar but show small species-specific variations, most noticeably in the 14th-18th orders. Tendons of birds also give meridional patterns that are similar to each other, but the avian patterns differ considerably from the mammalian ones. Avian tendons give stronger odd and weaker even low orders, a feature consistent with a reduced gap:overlap ratio, and have a distinctive intensity pattern for the higher meridional orders. Interpretation of these differences has been approached using biochemical data, diffraction by reconsituted fibers of purified collagen, and Fourier transform analysis. From these methods, it appears that the variations observed in the lower orders (2nd-8th) and in the higher orders (29th-52nd) are probably related to differences in the primary structure of the Type I collagen found in the different species. The variations observed in the 14th-18th orders appear not to be related to features within the triple-helical domain of the molecule.Equatorial diffraction yields information on the lateral packing of collagen molecules in the fibrils, and considerable variation was seen in different tendons. Rat tail tendon gives sharp Bragg reflections, demonstrating the presence of a crystalline lateral arrangement of molecules in the fibril. For the first time, sharp lattice reflections similar to those in rat tail tendon have been observed in nontail tendons, including rat achilles tendon, rabbit leg tendon, and wing and leg tendons of quail. In the rabbit and quail tendons, one of the strong equatorial reflections characteristic of the rat tendon pattern, at 1.26 nm, was absent. The positions of the equatorial maxima, which are a measure of intermolecular spacing, varied considerably, being smallest in the specimens displaying crystalline packing. The intermolecular distance in chiken and turkey leg tendons is longer than that found in mammalian tendons, or in avian wing tendons, which supports the hypothesis that a larger intermolecular spacing is characteristic of tendons that calcify.Thus, x-ray diffraction indicates there are reproducible differences in both the axial and lateral structure of collagen fibrils among different tendons. This work on tendon, a tissue containing almost exclusively Type I collagen as its major component, should serve as a basis for analyzing the structure of other connective tissues, which contain different genetic types of collagen and larger amounts of noncollagenous components.

Notizen: The conformation of poly(α-L-aspartic acid) was investigated on a sample in which β-bonds were not detected. CD and ir spectroscopy showed that poly(α-L-aspartic acid) passes through a conformational change induced by changes of the degree of ionization that is accompanied by precipitation; the precipitate is probably highly helical. The change was also detected by potentiometric titration.

Notizen: We studied the kinetics of the heat denaturation (at 50°C) of met-hemoglobin in the presence of various monohydric alcohols. The denaturation rate was slowed by the presence of small concentrations of methanol and ethanol; in all the other cases, i.e., at high concentrations of methanol and ethanol, and in the whole concentration range studied for iso- and n-propanol, an increase in the denaturation rate was observed. Following a procedure already applied to the study of the effects of the same alcohols on the reaction of hemoglobin with oxygen, we separated the overall observed effects into contributions related to the variation of the bulk dielectric constant of the medium (bulk-electrostatic contributions) and contributions not related to variations in this parameter (nonbulk-electrostatic contributions). For all the alcohols, we found a unique correlation law connecting the above nonbulk-electrostatic contributions with the analogous ones previously reported for the T → R transition of hemoglobin. This fact strongly supports the validity of the procedure used and suggests that nonbulk-electrostatic contributions, relative to these two different processes, have a common background and are univocally determined by the extent of the “solvent perturbation” imposed by the presence of the perturbing cosolvents.

Notizen: 2,2,′,2″,2‴-Tetrapyridineiron(III) complex ions anchored to poly(L-glutamate) (FeL) or poly(D-glutamate) (FeD) were used as catalysts for the H2O2 oxidation of L(+)-ascorbic acid at pH 7 and varying complex:polymer-residue molar ratios [C]/[P]. Evidence is produced that the reaction is a composite process reflecting contributions from parallel pathways, one of which corresponds to a catalytic route and is [H2O2]-independent and the other to an uncatalyzed electron-transfer process between the ascorbate anion and hydrogen peroxide. Stereospecific effects in the catalysis are observed on increasing the complex:polymer ratio, which corresponds to an increase of the amount of α-helical fraction in the polypeptide supports (xa). Thus, at [C]/[P] = 0.01 (xa 〈 0.05), kFeD/kFeL = 1.0; but at [C]/[P] = 0.20 (xa ≈ 0.70), kFeD/kFeL = 4.0 ± 0.5, kFeD and kFeL being the second-order rate constants of the electron-transfer reaction between the FeD or FeL isomer of the asymmetric catalyst and the L-ascorbate anion. The activation energies were found to increase markedly on going from the former to the latter complex:polymer ratio but, at the same time, to exhibit equal values with both enantiomeric catalysts. Stereoselectivity therefore appears to be an entropy-controlled process, arising from the conformational rigidity of the precursor complex, which very likely sees the substrate molecules bound to the chiral residues of the ordered polymer surrounding the active sites. The implications of the stereochemical features of the substrate-catalyst adduct on the mechanism of electron transfer are also discussed. Evidence is presented that the asymmetric [Fe(tetpy)(OH)2]+-polyelectrolyte systems play the additional role of environmental controller of the uncatalyzed oxidation of the L-ascorbate anion.

Notizen: A temperature-jump relaxation study of the interaction of tilorone with different polynucleotides and DNA has been performed. A single relaxation time, attributed to the intercalation step, has been observed in the case of poly[d(A-T)]·poly[d(A-T)], poly[d(A-C)]·poly[d(G-T)], poly[d(G-C)]·poly[d(G-C)], and poly(dG)·poly(dC). No intercalation into poly(dA)·poly(dT) occurs, and the interaction with poly(dG)·poly(dC) is different from what is observed with the other intercalating homopolymers. Refinement of the binding model is suggested from the analysis of the kinetic data. The relaxation curves obtained with DNA are well simulated based on a binding mechanism where DNA is considered a heterogeneous lattice and each type of site behaves as if it were located in the corresponding homopolymer. Poly(dA)·poly(dT) shows a unique behavior: studies of the effects of concentration and temperature indicate that tilorone acts as a probe of a process involving the polynucleotide alone. This process appears to be related to the dynamic structure of the nucleic acid and is detectable only when the bound dye is not intercalated.

Notizen: We had earlier observed that the detailed nature of the β-structure adopted by poly(L-tyrosine) depends on molecular weight [Auer, H. E. & McKnight, R. P. (1978) Biochemistry 17, 2798-2805]. It was proposed that shorter molecules form an open, single-layered sheet (class I) and that longer chains fold over to generate at least two layers (class II). In this work, solvent perturbation difference spectroscopy of the chromophoric side chain was applied to gain additional support for the model. Two sample-reference pairs of media, sodium acetate vs sodium chloride and urea vs buffer, were studied. Great care was taken to achieve identical conditions in the sample and reference cells. The factors of importance in executing the experiments are the polypeptide concentration, the degree of side-chain ionization, achievement of the same class of β-conformation, and the absence of significant aggregation. Difference spectra obtained with both solvent pairs have similar features. Low-molecular-weight samples manifest difference bands arising from both ionized and neutral tyrosine side chains, while high-molecular-weight samples yield spectra with contributions primarily from ionized residues. The interpretation of these results is that the class I particle has both ionized and neutral residues exposed to the solvent medium, whereas the class II particle is folded, with neutral residues restricted to the interior of the fold and primarily ionized residues on the outer surfaces exposed to the solvent. Our results, therefore, corroborate the original model.

Notizen: Extinction angles, flow birefringence, and intrinsic viscosities are compared for linear, bihelical DNAs from viral and other sources that span a range in molecular weight from ∼105 to 1.3 × 108. This range effectively spans the region over which transition from rigid-rod to expanded-coil hydrodynamic property behavior occurs. All DNAs are in identical, phosphate-EDTA, neutral-pH buffers, 0.1M in NaCl. The extinction angle is a hydrodynamic property only and is thus particularly sensitive to effects of kinetic chain rigidity or internal viscosity. Our extinction angle results cannot be interpreted by any simple, single-function theoretical expression. Rather, they must be divided into distinct high- and low-molecular-weight domains. The low-molecular-weight region is typical of rigid-particle opticohydrodynamic property behaviour characterized primarily by particle orientation. The high-molecular-weight domain shows evidence for a finite internal viscosity effect, however, which can be interpreted as very nearly Kuhnian using Cerf's amplification of the Gaussian subchain model to include internal viscosity. It is found that the high-molecular-weight, monodisperse viral DNAs from T7, T5, and T2 bacteriophage show an internal viscosity contribution to the limiting extinction angle-shear rate ratio of ∼3 × 10-3 s. An effect of this magnitude may be marginally important in interpreting extinction angle and certain other hydrodynamic property data for high-molecular-weight DNA systems. Internal viscosity effects do not appear to be manifest in the ratio of flow birefringence to intrinsic viscosity, however, and the persistence length of the high-molecular-weight DNAs is found to be independent of molecular weight to within estimated experimental uncertainty.

Notizen: Phosphorylase kinase contains four approximately equivalent binding sites for 1-anilinonaphthalene-8-sulfonate (1,8-ANS). Measurements of the time decay of fluorescence anisotropy have failed to give any indication of internal degrees of rotational freedom involving a significant portion of the tertiary structure. In the presence of 1 mM Ca2+, calmodulin binds one molecule of 1,8-ANS. No binding occurs in the absence of Ca2+. The binding is strongly temperature-dependent, a decrease in binding occurring with increasing temperature. Determinations of the time decay of fluorescence anisotropy indicate the presence of internal rotations, which become more important with increasing temperature. Complex formation between phosphorylase kinase and calmodulin reduces the binding of 1,8-ANS.

Notizen: The dissociation of beef liver and bacterial (Micrococcus lysodeikticus) catalases by the action of sodium n-dodecyl sulfate (SDS) has been investigated as a function of SDS concetration and time by ultracentrifugation. The rate of dissociation of beef liver catalase is found to be much faster than that for bacterial catalase in 25 mM SDS at pH 7.0. Beef liver catalase is dissociated into its four subunits after 24 h, whereas bacterial catalase is not completely dissociated after 36 days of incubation. The binding of SDS to beef liver catalase obeys a Hill equation with a cooperativity exponent of 2.0 and a binding constant of 440. The initial interaction of SDS with beef liver catalase can be detected by microcalorimetry, whereas the mixing of SDS with bacterial catalase is athermal. Bacterial catalase retains enzymic activity in the presence of SDS, whereas beef liver catalase is completely deactivated at SDS concentrations above 5 mM. Beef liver catalase is more sensitive to acid denaturation than bacterial catalase, and the rate of dissociation for both catalases is sixth-order in proton concentration. Comparison of the amino acid analysis of the two catalases shows that bacterial catalase has a smaller number of lysyl residues and a larger number of glutamyl residues than beef liver catalase. Taken together these structural differences could lead to a reduced affinity of bacterial catalase for the binding of SDS as observed.

Notizen: The Avileurekanoses A and C and Further Degradation Products of the Avilamycins A and CAlkaline hydrolysis of the orthosomycin antibiotics, avilamycins A ad C products similar t those earlier described for flambamycin. Among these avileurekanose c (15) became of particular importance because its acetate prisms suitable for an X-ray structural determination. For the avilamycins A and C structural formulae 2 and 3, respectively, can now be drawn, in which only the configuration at C (16), one out of 32 asymmetric C-atoms, is not yet determined.

Notizen: The complexation of Cue2+ with 1, 8-diamino-3, 6-diaza-2, 7-octanedione (—N, N′-diglycyl-1, 2-ethanediamine, DED) and with 1, 9-diamino-3, 7-diaza-2, 8nonanedione (—N, N′-diglycyl-1, 3-propanediamine, DPD) has been studied by potentiometric and by spectrophotometric titration. With both ligands L the complexation to Cue2+ leads to relatively complicated equilibria with CuLH3+, CuL2+, CuLH-2, and dimeric Cu2L24+ complexes. With DED, another dimeric species, Cu2L2H-22+, is formed in addition. Independent numerical treatment of spectrophotometric and poteritiometric titrations was used to obtain a satisfactory model for the complexation and to test the relative discriminatory power of the two methods. Titrations of glycine ethylamide (GEA) were used as an additional test and as a model for DED and DPD. It was shown that in each case spectrophotometric titrations give results of similar reproducibility and have a discriminatory power equal to or better than potentiometric titrations, provided that optimum mathematical algorithms are used in the numerical treatment.

Notizen: Heterocyclic and Carbocyclic 12-π-and 14-π-Systems, 47th Commnunication1. Synthesis of 7,9-Dimethyl-4,5-dihydro-3H-benz[cd]azualene-3-one and 7,9-Dimethyl-3H-benz[cd]azulene-3-one. A Simple Synthesis of Azulenopseudophenalenons4, 6, 8-Trimethylazulene (3) reacts after metalation with lithiumdiisopropyl-amide in ether with bromoacetic acid to the 6, 8-dimethylaltulene-4-propionic acid (4), which undergoes cyclization to the 7, 9-dimethyl-4, 5-dihydro-3H-benz [cd]-azulene-3-one (5) in the presence of p-toluenesulfonic acid; oxidation of 5 with 2, 3-dichloro-5, 6-dicyanobenzoquinone yields 7, 9-dimethyl-3H-benz [cd]azulene-3--one (1b). Alkylation of 1b with triethyloxonium tetrafluoroborate in CH2C12 gives the 3-ethoxy [cd]benzazulenium tetrafluoroborate (6).

Notizen: Doubts that have recently been expressed [1] about the currently accepted (+)-(R), (-)-(S) [2] absolute configuration of indane-1-carboxylic acid appear to be unwarranted. Our ORD. values for 1-methylindane [12] are in error.

Notizen: Synthesis of [16,16,16,16′,16′,16′ 2H6]LycopeneLycopene having at both ends the deuteriated methyl groups trans to the chain has been synthesized for further biochemical experiments aimed to elucidate the stereochemistry of the cyclization step.Incidentally a gas-chromatographic separation of the isotopisomers 1 and 2g has been observed.

Notizen: The dienone-dianion derivatives 1 react with all types of electrophiles tested (alkyl halide, silyl chloride, ester, ketone, aldehyde, epoxide) to give β, γ-unsaturated carbonyl compounds of type A (see Formulae 2-6, 13, 14 and Tables 1-5). The α- and β-hydroxyalkylation products obtained from 1a-1d can be converted to tetra-hydrofuran and tetrahydropyran derivatives 7 and 16, respectively (Tables 1 and 2), those from the sulfur analogues 1e and 1f to ketene thioacetals 9 and to dienone derivatives 10 and 12. The t-butyl and α-hydroxy-ketones are cleaved to give nitriles, amides, carboxylic acids and esters (Formulae 16-25). The reagents 1 allow to synthesize products with distant functional groups in one step (cf. 1,8-diketones 14 and Formulae 26-30); they correspond to the d5-synthons 31-33; in Table 6, they are compared with other d5-reagents.

Notizen: Methyl-2-acetamido-4,6-di-O-acetyl-3-S-acetyl-2-deoxy-3-thio-α-D-mannopy-ranoside has been synthesized by conversion of methyl 2-amino-2-deoxy-4,6-O-benzylidene-α-D-altropyranoside into the corresponding 3-O-methanesulfony1-2-N-[(methylthio)thiocarbonyl]derivative followed by intramolecular displacement of the 3-O-methanesulfonyloxy group with the (methylthio)thiocarbamoyl group.

Notizen: (Perhalomethylthio)heterocycles XII. Preparation of Perfluoroalkylsulfonylurea Derivatives as well as CCl3-nFnX-Substituted Heterocycles and Their Biological ActivityXI, Mitt., s.[1]In the presence of CF3SO3H (chlorodifluoromethylthio)thiophene 1 reacts with CClF2SCl to give the 2,5-disubstituted thiophene 2a which on oxidation with 30% H2O2-solution yields the corresponding sulfonyl compound 2b · R1SO2NCO adds amines to give R1SO2NHC(O)NHR 3a-g. Some biological properties of these compounds were investigated.

Notizen: The stereochemical outcomes [ratios (1 R, 2 R, 4 R)-isoborneol/(l R, 2 S, 4 R) isborneol or (1R, 2 S, 4 S)-isoborneol(l S, 2 R, 4 S)-borneol and (1 RS, 2 RS, 4 RS)-isoborneol/(l RS, 2 SR, 4 RS)-borneol] in lithium, sodium and potassium/ammonia reductions without a proton source of the enantiomeric [(1 R, 4 R) or (1 S, 4 S)] and racemic (1RS, 4RS) forms of camphor under the same conditions differ strongly. This explains contradictory reports in the literature and, in the case of the reductions with potassium in which pinacol coupling does not compete, proves that the reductions involve bimolecular reactions between two ketyls, or between the ketone and the ketyl or the ketone dianion.

Notizen: Investigation of the formation of complex reaction products in the gas-phase system O3/NO2/(Z)-2-butene by combination of linear reactors with IR. matrix and microwave Stark Spectroscopy is reported. Besides the polyatomic products observed earlier in the gas-phase ozonolysis of (Z)-2-butene, the following products were identified; N2O5, HNO3, HNO4, CH3NO2, CH3ONO, CH3COONO2 and CH3COO2NO2 (peroxyacetyl nitrate, PAN). Matrix IR. spectra of N2O5, HNO3. CH3COONO, CH3COONO2 required for reference purposes are presented. It is shown that PAN-formation occurs already in the absence of light. A reaction scheme is proposed for explanation of the observed complex NOx-containing products, which assumes methyldioxirane as a central intermediate. Particular reaction steps of the scheme will be discussed, including thermochemical estimates of reaction enthalpies.

Notizen: A series of lipophilic N, N, N′,N′-tetrasubstituted diamides were prepared and their selectivity in solvent polymeric membranes was studied, cis-N, N, N′, N′-Tetraisobutylcyclohexane-1,2-dicarboxamide induces a selectivity in membranes for Li+over alkaline earth metal cations and other alkali metal cations by a factor of about 1000 and 100 respectively. The ionophore N, N′-diheptyl-N,N′-dimethylethylmalonamide is an attractive candidate for the use in microelectrodes for the determination of intracellular Mg2+-activities.

Notizen: Syntheses of Sulfonated Derivatives of 4-FluoroanilineSynthesis of 2-amino-5-fluorobenzenesulfonic acid (2) was achieved by baking the hydrogen sulfate of 4-fluoroaniline (1). Sulfonation of p-fluoroacetanilide (4) with oleum followed by hydrolysis gave 5-amino-2-fluorobenzenesulfonic acid (3). The same reaction with 1 yielded 3 in an impure state. The structures of 2 and 3 were confirmed by converting the diazonium chlorides derived from 5-fluoro-2-nitroaniline (5) and from 2-fluofo-5-nitroaniline (8) to 5-fluoro-2-nitrobenzene-sulfonyl chloride (6) and 2-fluoro-5-nitrobenzenesulfonyl chloride (9), respectively, followed by hydrolysis of 6 to 5-fluoro-2-nitrobenzenesulfonic acid (7), and of 9 to 2-fluoro-5-nitrobenzenesulfonic acid (10), and by final reduction. Compound 10 was also obtained by sulfonation of 1-fluoro-4-nitrobenzene (11) with oleum.

Notizen: The radical anion of 1,1,2.2,9,9,10, 10-octafluoro[2.2]paracyclophane (1) has been generated by electrolytic reduction of 1 in 1,2-dimethoxyethane (tetrabutylammonium perchlorate as the supporting salt). The hyperfine coupling constants of the eight 19F-nuclei and the eight protons, af = 3.35 and aH ≈ 0.10 mT, are qualitatively reproduced by INDO. calculations. According to these calculations, the singly occupied orbital of 1⊖ can be represented by an Ag-combination of two ‘symmetric’ benzene LUMO's, with a substantial transfer of spin population into the 2s-AO's of the F-atoms. Line-width alternation in the ESR. spectrum of 1⊖ indicates an ion pairing of the radical anion with its counter-ion Bu4N⊖. The energy barrier to the migration of the cation between two equivalent sites at the radical anion is determined as 14±2 kJ/mol.

Notizen: The rate of DMF exchange on [Tm (DMF)8]3+ has been determined by 1H- and 13C-NMR. linebroadening techniques. 1H-NMR. yields the following solvent exchange parameters; ΔH* = 33.2 (±0.5) kJ mol-1, ΔS* = 9.9 (±2.4) J K-1 mol-1and k (200 K) = 2.94 (±0.09)× 104 s-1, whilst results from 13C-NMR. are similar. No evidence, by 35C1-NMR., was found of contact ion-pair formation when the perchlorate salts were used.

Notizen: Crystal and Molecular Structure of Macrocyclic Musks. I. cis-Civetone and polymorphous α- and β-forms of his 2,4-dinitrophenylhydrazonecis-Civetone (C17H30O) forms tetragonal plastic crystals, space groupe 141; a = 9.95(4), c = 32.79(1) Å; Z = 8. The plastic phase exists in a wide temperature range and 731 reflexions could be collected at 153 K. The highly disordered structure model was obtained by the use of direct methods. The molecules appear as ring-shaped diffuse electron-density distributions located in special position.Two polymorphous crystalline forms were isolated for the 2,4-dinitrophenyl-hydrazone of cis-civetone (DNPHCC). Both forms are triclinic, space group P1. Z = 2 (α-Form: a = 6.279(5), b = 12.605(8), c = 15.253(10) Å, α = 105.49(7). β = 100.31 (6), γ = 91.23(7)°; β-Form: a = 7.950(2). b = 8.405 (2). c = 18.233(4) Å, α = 100.28(2), β = 92.29(3), γ = 94.18(2)°). The structures were solved by direct methods and refined to R = 0.11. Each polymorph is associated with a different quinquangular conformation of the macrocycle. In the crystals the intermolecular interactions between macrocycles and aromatic substituents are minimized, the DNPH group being oriented in a face-to-face arrangement across a centre of symmetry.Empirical force field calculations show that the overall intluence of the DNPH moiety on the attached cycle does not significantly modify its conformation with regard to that of the ketone itself.

Notizen: The interaction of solvents and of unidentate ligands such as N3-, SCN-, OCN- and OH- with the Co2+-, Ni2+ and Cu2+-complexes of 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane (TMC) have been studied by Spectrophotometric and calorimetric techniques. The spectra in different solvents (Table 2) show that the Ni2+- and probably also the Cu2+-complex with TMC exist as square planar or pentacoordinate species or as a mixture of both, depending on the donor properties of the solvent. The [Co(TMC)]2+-complex is pentacoordinate in all the solvents studied.Ternary complexes [M(TMC)X]n+ are also formed by the unidentate ligands X = N3-, OCN-, OH-, F- and NH3 and their stability constants have been determined. Interesting is the high selectivity of [Ni(TMC)]2+ towards the addition of a further donor (Table 3). Only small ligands such as those listed above form stable adducts, whereas the larger ones such as imidazole or pyridine do not. This is a consequence of the special structure of the complex and of the trans-I-(RSRS)- conformation of the ligand in these complexes. Since the four methyl groups are all on the side of the macrocycle to which the additional unidentate ligand binds, steric interaction between the four methyl groups and the larger ligands prevents the formation of the adducts.The calorimetric measurements show that the stability of the complexes [M(TMC)X]n+ is due to both an enthalpic and entropic contribution which differ in their magnitude (Table 4). This indicates that several antagonistic factors are important in determining the overall stability.

Notizen: The structures of two new bitter triterpenes, ganoderic acid A and B. isolated from a mushroom Ganoderma lucidum (FR.) Karst. (Polyporaceae) were determined as 1 and 2 on the basis of spectral data. Ganoderic acid A is a novel highly oxidized triterpene bearing a boat-shaped A-ring of lanostane.

Notizen: Crystal and Molecular Structure of Macrocyclic MUSKS. II. trans-Civetone and its 2, 4-DinitrophenylhydrazoneThe trans and cis isomers of civetone (C17H30O) crystallize in isomorphous systems and form plastic crystals (tetragonal, space group I41 a=9.95 (4), c = 32.79 (1) Å, Z = 8). Mixed crystals were prepared with cis-civetone as second component. Accordingly the diffuse structural model obtained for the disordered phase of the cis-isomer [1] is also regarded as representative of that of trans-civetone.The crystal structure of trans-civetone 2,4-dinitrophenylhydrazone (DNPHTC; C23H34N4, Monoclinic, Space group P21/c, a=8.364(2), b=7.971(1), c=36.025(8) Å, β=91.44 (2)°) was solved by direct methods and refined to a final R of 0.09 (Rw = 0.021). The macrocycle adopts a sexangular conformation [23*434*44*], and its mean plane is approximatively perpendicular to that of the aromatic substituent. Empirical force field calculations have shown that the DNPH substituent has very little influence on the macrocycle conformation. The intermolecular interactions take place essentially between groups of the same type: macrocycle…macrocycle and DNPH…DNPH.

Notizen: The synthesis of a series of substituted 1-benzyl-3,4-dihydroisoquinolines by Bischler-Napieralski cyclization is described. Competitive methylene blue sensitized photo-oxygenation experiments allowed the determination of relative rates of photo-oxygenation of 1-benzyl-3,4-dihydroisoquinolines, Substituents were shown to affect both the equilibrium concentration of the tautomeric enamine and the overall photo-oxygenation rate. After correcting for differences in enamine concentration, the relative rate data provided a diagnostic probe of the reaction mechanism, which involves transfer of charge in the rate-limiting step.

Notizen: The temperature- and pressure-dependent equilibria for the addition of an extra N, N-dimethylforrnamide (DMF) or trimethylphosphate (TMP) ligand onto [Nd (DMF)8]3+- and [Nd(TMP)6]3+-species respectively have been measured by visible spectrophotometry. Complementary NMR. studies on other lanthanide ions show a gradual shift in preference for the lower coordination number across the lanthanide series.

Notizen: Stereoselective syntheses of 2exo, 3exo-bis (chloromethyl)-5-[(Z)-chloromethylidene]- (9), 2exo, 3exo-bis (chloromethyl)5-[(E)-chloromethylidene]- (10) and 2exo, 3exo-bis(chloromethyl)-5-[(E)-methoxymethylidene]-6-niethylidene-7-oxa-bicyclo[2.2.1]heptane (13) are presented. Double elimination of HCI from 9, 10 and 13 yielded 2-[(Z)-chloromethylidene]- (14), 2-[(E)chloromethylidene]- (15) and 2-[(E)-methoxymethylidene]-3,5,6-mmethylidene-7-oxabicycio[2.2.1]heptane (18), respectively, without loss of the olefin configuration. Ethylene tetracarbonitrile (TCE) and N-phenyltriazolinedione (NPTAD) added to these new exocyclic dienes and tetraenes preferentially onto their exo-face. The same face selectivity was observed for the cycloadditions of TCE to the (Z)- and (E)-chlorodienes 9 and 10, thus realizing a case where the kinetic stereoselectivity of the additions is proven not to be governed by the stability of the adducts. The exo-face selectivity of the Diels-Alder additions of dienes grafted onto 7-oxabicyclo [2,2.1]heptanes contrasts with the endo-face selectivity reported for a large number of cycloadditions of dienes grafted onto bicyclo[2.2.1]heptane skeletons.

Notizen: The rates of photo-oxidation of exocyclic S-cis-butadienes grafted onto bicyclo-[2.2.1]heptanes and 7-oxabicyclo[2.2.1]heptanes (1-6) are dependent upon remote modifications of the bicyclic skeletons. They correlate with the rates of Diels-Alder additions of these dienes to strong dienophiles. The 2,3-dimethylidenenorbornane (1), 5,6-dimethylidene-2-norbornene (2) and 2,3-dimethylidene-7-oxanorbornane (3) gave the corresponding endo-peroxides (3,6-dihydro-1,2-dioxines) 7-9 in good yield. The 2, 3, 5, 6-tetramethylidene-7-oxanorbornane (4) gave the mono-endo-pe-roxide 6, the latter did not react with a second equivalent of oxygen. Similarly, 5, 6-dimethylidene-7-oxa-2-norbornene (5) was unreactive toward photo-oxidation. Thermal isomerization of the endo-peroxides 7 and 9 gave, the trans-diepoxides 10 and 14, respectively, with high stereoselectivity. The endo-peroxides 6, 7 and 9 were cleanly isomerized into the corresponding α, β-unsaturated γ-hydroxy aldehydes in the presence of catalytic amounts of Rh2(CO)4Cl2.

Notizen: Synthesis and Circular Dichroism of Optically Active Carotenoid ModelsThe synthesis of the following optically active carotenoidic model compounds are described: ( - )-(3,S,3′S)-3,3′-diisopropenyl-16,17,18,16′,17,18′-hexanor-β,β-carotene (1), (3R,3′R)-19,20,19′,20′-Metranor-zeaxanthin (2) and (6R,6′R)-19,20, 19′,20′-tetranor-ε,ε-carotene (3). These compounds were synthesized for the following reasons: (1) the presence of methyl groups at C(1), C(1′), C(5), C(5′) of cyclic carotenoids profoundly affects the torsional angle of the C(6), C(7)- and C(6′), C(7′)-bonds. Sign and magnitude of this angle are, according to recent theories [4] [5], responsible for a helical chromophore and for strong conservative [4] Cotton effects. CD. measurements of 1 give experimental support to these state- 1 exhibits weaker and less temperature dependent Cotton effects. Of more significance, the shape of the curve is no longer conservative, as expected. This constitutes experimental evidence for the contention that the β-endgroups and the polyene chain indeed form an inherently dissymmetric chromophore in optically active β, β-carotene derivatives; (2) the slightly S-shaped form of the polyene chain of carotenoids, shown by X-ray analyses [12] [13], is mainly ascribed to the presence of the methyl groups in the chain. Models 2 and 3 therefore are assumed to be linear. CD. studies of these compounds should consequently give information about the influence of deviation from Linearity and planarity of the polyene on the CD. spectra of carotenoids. CD measurements of 2 and 3 show that the lack of methyl groups does not alter the general type of the curve. Only the intensity and to some extent the position of the Cotton effects are influenced. Carotenoids with the ε-endgroup possess inherently symmetric but asymmetrically distorted chromophores.The assumption that non-conservative CD. spectra could become conservative upon cooling [4] is experimentally confirmed by model 3.The rule stating that pairs of all-(E) and mono-(Z) isomers of carotenoids with only one cyclic endgroup should have CD. spectra with the same sign [5] is disproved by the CD. spectra of four stereoisomeric rubixanthins (s. Fig. 5).The UV./VIS. spectrum of 3, λmax 447 (ε 216000), 418 (ε 189000) exhibits the highest molecular extinction ever reported for a carotenoid.

Notizen: Technical Procedures for the Synthesis of Carotenoids and Related Compounds from 6-Oxo-isophorone, VI. Synthesis of Rhodoxanthin and (3RS, 3′RS)-Zeaxanthin; Routes to the C15-Ring Component via 3-Oxo-ionone DerivativesThe C15-ring component 4, key intermediate of a new scheme for the synthesis of rhodoxanthin (1) and (3RS, 3RS)-zeaxanthin (3), has been synthesized starting from 6-oxo-isophorone (7) via 3-oxo-cyclocitral and 3-oxo-ionone derivatives.

Notizen: Crystal and Molecular Structure of Macrocyclic Musks. III. Muscone and its 2, 4-DiuitrophenylhydrazoneMuscone (3-methylcyclopentadecanone C16H30O) forms orthorhombic plastic-crystals with Z = 2 (a = 5.560(4), b = 8.176(6), c = 17,168(20) Å). Single crystals are obtained by zone melting at 258 °K. The high degree of disorder and the ambiguity of space group have precluded a structural determination by X-ray diffraction methods.The crystal structure of muscone 2,4-dinitrophenylhydrazone (DNPHM; C22H34N4O4, triclinic, space group P¯, a = 8.015 (4), b = 8.235 (2), c = 17.409 (4) Å. α = 102.69 (4), β; = 93.86 (3), γ = 96.03 (3)° Z = 2) was solved by direct methods and refined to a final R of 0.155 (Rω = 0.102). The macrocycle shows static disorder, which could be partially resolved by analysis of the anisotropy of the atomic vibrational parameters. Eight possible conformers with reasonable geometries emerged from the subsequent refinements and were used as starting models in force-field calculations, which converged to four quinquangular conformations ([25233]; [34233]; [21423*4]; [3423*4]) with similar energies. In the molecular packing, the interactions between macrocycles and substituents are minimized. They are comparable to those described for the cis- and trans-civetone DNPH derivatives [1] [2].

Notizen: Two new types of iso-oxacephems have been synthesized in which a phosphonate group replaces either the carboxyl group or C(3). The latter compound exists as a stable trialkoxyphosphonium ylide.Potassium thioacetate and O2 in DMF are transformed in an autocatalytic, probably sulfur-catalyzed process to CH3COOK and sulfur; the latter two reagents are sufficient to transform the methanesulfonate 7 to the isopenam 15.

Notizen: The synthesis of some β-lactams and one Δ1-carbapenem is described. The electronic activation of monocyclic β-lactams of type 1 is not sufficient to generate a bioactive compound.

Notizen: Reactions of [2N]cyclophanes (N = 2,⃛6) with solvated electrons in 1,2-di-methoxyethane at 193 K have been studied by ESR. and ENDOR. spectroscopy. All but the two most highly bridged cyclophanes (N = 5 and 6) are reduced to paramagnetic species under these conditions. Whereas the radical anions of [2.2]-paracyclophane and [23](1,2,4)- and [24](l,2,4,5)cyclophanes are sufficiently persistent to be characterized by their hyperfine data, those of the remaining five cyclophanes undergo a rapid cyclization to the radical anions of 4,5,9,10-tetrahydropyrenes. These have been identified as the unsubstituted tetrahydropyrene (from [2.2]-metacyclophane and [23](l,2,3)cyclophane), the 2,7-dimethyl-derivative (from [23](1,3,5)- and [24](l,2,3,5)cyclophanes) and the 1,8-dimethyl-derivative (from (24l,2,3,4)cyclophane). The persistence of the cyclophane radical anions seems to depend on the numbers, nmeta and npara, of the meta-and para-positions of the bridging ethano groups in the two benzene rings. The prerequisite for the radical anion to be persistent is nmeta≤npara.

Notizen: The X-ray crystal structure analysis of the 17,18-di-O-acetyl derivative of the antibiotic aspochalasin C (monoclinic, a = 26.377, b = 10.840, c = 11.937 Å, β = 102.08°, space group C 2) confirms the constitution elucidated by spectroscopic methods and chemical degradation, and establishes the relative configuration.

Notizen: An improved synthesis of the isomeric 12- and 14-chlorodehydroabietic acids (3 and 2, respectively) and 12,14-dichlorodehydroabietic acid (4) is described. The monochioro isomers were conveniently separated as the imidazole derivatives, and conversion of the latter to the free acids or their corresponding methyl esters could be achieved in high yield. Studies involving microbial degradation of 2-4 are underway.

Notizen: One of the fish-toxic chlorinated resin acids, 14-chlorodehydroabietic acid (5), found in kraft mill effluent is examined. When exposed to the fungus Mortierella isabellina, 5 is converted into a number of hydroxylated derivatives which show low levels of toxicity to fish. These biotransformation products were isolated and characterized.

Notizen: Syntheses and Chemical Properties of New ‘Donor-Acceptor’-stahilized Molecular Systems with a Central Bicyclo[4.4.1] undeca-l(10).3,6,8-tetraene-2,5-diylidenc GroupThe synthesis of X-methyl-2-(5-oxobicyclo[4.4.1]undeca-l)10(,3,6,8-tetraen-2-yliden)-l,3-benzodithiol (4) is described starting with the keto-enol mixture 2 and 5-methyl-1,3-benzodithiolium perchlorate. Under rearomatization of the central frame protonation of 4 yields the salt 4c. The reaction of 4 with dicyanoketene gives the ‘push-pull-substituted’ 5, and with 9-carbonylfluorene the fulvalene derivative 7, which can be protonated by CF3CO2H at C(9″) to the salt 8. The reaction of 2-methylthio-l,3-dithiolium jodide 9 with the keto-enol mixture 2 yields 10, which, on protonation at the carbonyl group by CF3CO2H, gives the salt 11 under rearomatization. The spectral data of the new compounds 4, 4c, 5, 7, 8, 10 and 11 are reported and discussed.

Notizen: The synthesis of an iso-oxacephem is described. Reaction of methanesulfonyl chloride with hydroxyaldylmalonates can form sulfones or sulfonates, their ratio varying with the basicity of the tertiary amine used in the sulfonation.

Notizen: The synthesis of the title compound is described.

Notizen: The water exchange of [V(H2O)6]Cl2 in aqueous solution has been studied as a function of temperature and pressure (up to 250 MPa), by measuring the 17O-FT-NMR. line-widths of the free water resonance at 8.13 MHz. The kinetic parameters obtained are K298m = 87±4 s-1, ΔH* = +61.8 ± 0.7 kJ mo1-1 and ΔS* = -0.4±1.9 J mol-1 K-1. A pressure-independent volume of activation ΔV* = -4.1±0.1 cm3 mol-1 is obtained, suggesting an associative interchange (Ia) mechanism for this early divalent metal ion.

Notizen: A total synthesis of racemic 3-deoxy-7,8-dihydromorphine ((±)-2) and 4-me-thoxy-ALmethylmorphinan-6-one ((±)-3) is described. The key intermediate was 2,4-dihydroxy-N-formylmorphinan-6-one (11), obtained from 3,5-dibenzyloxy-phenylacetic acid (4) in 41.8% overall yield. Bromination of 11, and treatment with aqueous NaOH-solution afforded, after N-deblocking and reductive N-methylation with concomitant removal of the aromatic bounded Br-atom, the morphinanone 14. Elimination of the HO-C(2) group in 14 was accomplished by hydrogenolysis of its N-phenyltetrazolyl ether 15, to give 3-deoxy-6,0-didehydro-7,8-dihydromorphine (16). Reduction of 16 with L-Selectride at low temperature provided (±)-2 in high yield. The ether 15 directly afforded, under more vigorous reduction conditions, 4-hydroxy-N-methylmorphinan-6-one (17). and after O-methylation of 17, the methyl ether (±)-3 was obtained. A (1:l)-mixture of 4-hydroxy-2-methoxy-N-methylmor-phinan-6-one (28) and its 2-hydroxy-4-methoxy isomer 30 svere obtained by Grewe-cyclization of a mono-methoxylated aromatic precursor similar to that which afforded 11. The 2,4-dioxygenated N-methylmorphinan-6-ones 29, 31 and 38 were also prepared and characterized.

Notizen: Crossconjugated Cyanines and Meroeyanines, Obtained from Salts of 1-Substituted 2,3-Dimethylquinoxslines. 2nd Communication. On the Syntheses of Dehydro-FormsProducts 3 of the readily oxidized 1 and 2 are found to be sensitive to solvolysis, especially when X and R are electron-withdrawing substituents. In some cases, the salts 3 could be identified as the oxidation products of the salts 9. The oxidation of 9p (X = 5,6-benzo, R=CH3) by an alkaline solution of K3Fe(CN)6 leading to the quinoxalinone 10p is compared with the voltammetric oxidation of 81 (X = H, R=4-C1C6H4) and related to Viehe's [15] c, d-stabilized radicals. 1H-NMR.-spectra of the salts 3 are discussed with regard to the (E/Z)-isomers,

Notizen: Iridoids from Verbascum nigrum L.Two new iridoid glycosides, nigroside 1 ( = 6-O-(3-O-einnamoyl-α-L-rhamno-pyranosyl)aucubin (2), and nigroside 2 (=6-O-(2-O-cinnamoyl-α-L-rhamnopy-ranosyl)aucubin (3), and the known compound laterioside (1) have been isolated from extracts of the stems of Verbascum nigrum L., and their structures established primarily on the basis of NMR. spectroscopy. Harpagoside (4), a known iridoid glucoside, was also isolated from the roots of this plant.

Notizen: Isomers of lysergic acid derivatives (3, 22, 23 and 24). analogous to aporphine, have been synthesized from the key intermediate ketone 12.

Notizen: The synthesis of new 2-oxo-2,8-dihydro-[l,2,4]-oxadiazoo-[2,3-a] pyrimidine-carbamates 3 described in this paper is based upon a regioselective heterocyclization of the pyrimidine-2,6-bis (alkoxycarbonylamino) N-oxides 4. Structural and mechanistic aspects of that cyclizalion are discussed.

Notizen: The rate constants for 3-substituted adamantyl p-toluenesulfonates 3a-3k in ethanol/water 80:20 correlate well with the respective inductive substituent constants σIq. The reaction constant ρ for the toluenesulfonates 3 is 10% larger than for the corresponding bromides 2, indicating somewhat more charge separation in the activation of the toluenesulfonates. Evidence is presented that stabilization of the resultant 1-adamantyl cations by induction involves graded 1,3-bridging, which is favored when the substituent is an electrofugal group, and that stabilization by n-electron donors involves C, C-hyperconjugation. Rate ratios for the toluenesulfonates 3 and the bromides 1 exceed 103 and are almost independent of the 3-substituents. The implications of this are discussed in the light of current hypotheses.

Notizen: The syntheses of optically active t-butyl 2-(p-tolylsulfinyl)propionate and -butyrate (2a and 2b, respectively) are described, and it is shown that aldol-type condensation of the corresponding enolates is limited by steric hindrance. Optically active (2a) reacted, however, in high yield with aliphatic aldehydes and lead to 80% of asymmetric induction.

Notizen: Synthesis of 5,6-Ephnino-5,6-dihydro-β-iononeIn order to synthesize the title compound 5 the 2-azidoalcohols 3 and 4 were treated with various nucleophilic phosphorus compounds. It was found that the course of the reaction depends strongly upon the kind of nucleophilic phosphorus derivative used.

Notizen: Total synthesis of α-disaccharidyl-2,5,6-trideoxy-streptamines related to aminoglycoside antibiotics derived from maltose and lactoseThe synthesis of the hitherto unknown 4-O-substituted α-linked pseudo-tri-saccharides 1,2 and 3 is described. The key intermediates required in the reaction sequence are the glycals 12, 13 and 14, prepared from maltose, lactose and the chiral ditosyloxy-cyclohexanol 15, readily accessible from quinic acid. The pivotal step in the reaction's scheme - a stereospecific α-glycosylution procedure -, is an acid-catalyzed addition of the alcohol 15 to the glycals 12, 13 and 14 leading to the corresponding 2,3-unsaturated trisaccharides. The latter compounds were transformed to the target α-glycosides of 2,5,6-trideoxystreptamine 1, 2 and 3 which were devoid of significant antibacterial activity. These results indicate that the presence of an ether linkage at the position 4′ is probably critical for antibacterial activity.

Notizen: Asymmetric Michael-Additions Practically Completely Diastereo- and Enantloselective Alkylations of the Enamine from Cyclohexanone and Prolinyl Methyl Ether by ω-Nitrostyrenes to Give u2-(1′-Aryl-2′-nitroethyl)cyclohexanonesWhen the enamine (S)-N-(1′cyclohexenyl)-2-methoxymethyl-pyrrolidine is added to 2-aryl-l-nitroethylenes, only one of the four possible enantiomerically pure diastereomers is formed. Hydrolysis of the crude primary products furnishes α-alkylated cyclohexanones of 〉 90% e. e. (3, Scheme 3). Their (2S,1′R)-configuration was deduced by chemical correlation with l-cyclohexyl-l-phenyl-ethane and from an X-ray crystal structure analysis of (-)-(2R,3S,6′R1,l″S′)-3-methyl-N-[6′-(2″-nitro-l″-phenylethyl)-l′-cyclohexenyl]-2-phenylmorpholine (lla, Scheme 5 and Fig. 2). - The relative topicity of reactant approach with the prolinol derivative (see II) is specified as lkul-l,4. The steric course and the mechanism of the reaction are discussed.

Notizen: The reduction of a series of 1,2-dimethyl-3-indolyl heteroaryl ketones, where the heteroaryl components are 2-benzoxazolyl, 2-behzpthiuzolyl. 1-methyl-2-benz-imidazolyl, 4- and 2-pyridyl, in aprotic and prone solution are described by means of DC. and AC. polarography, cyclic voltammetry and coulometry.In acetonitrile a two-step reduction mechanism with a reversible first and an irreversible second one-electron transfer has been observed, confirmed by AC.-polarographic and cyclovoltammetric measurements. The reduction potentials, between -1.377 and -1.787 V for the first step, and between -1.937 and -2.250 V (vs. Ag/AgCl) for the second, could not be correlated with the LUMO energies from HMO calculations which was explained as being due to a distorted configuration of the π systems.In protic media (ethanol/water) reduction occurs in an irreversible one-step mechanism. Measurements of the pH dependence of the half-wave potential in the pH* range 0-12 and the evaluated transfer coefficients show that the reduction step represents the transfer of two electrons and two protons yielding secondary alcohols and no dimerization products under any condition. These findings are supported by coulometric and macroscale electrolysis of the ketones; the products isolated were characterized by IR. and 1H-NMR. data.

Notizen: The silylation of the surface of sodium borosilicate glass was investigated under conditions that might be applied to the fabrication of ion-selective microelectrodes of the liquid membrane type such as are used in physiology, Silylation was carried out for 15 min at different temperatures and with six different silanes. The hydrophobicity was measured and found to be greatest with reaction temperatures of 200-350°, the effectiveness of the different silylating agents being in the (increasing) order: trimethylchlorosilane, tributylchlorosilane, (dimethylamino)trimethylsilane, hexamethyldisilazane, dimethyldichlorosilane, bis(dimethylamino)dimethylsilane. The results give evidence of a catalytic effect of basic amine groups and show that the reactivity of the surface of freshly drawn glass is increased by acid leaching.

Notizen: 1-p-Menthene-8-thiol (B) is shown to be a potent character-donating constituent of grapefruit juice, in which it occurs at the ppb-level or below. A convenient synthesis is described for this terpene-thiol, apparently the most powerful flavor compound ever found in nature.

Notizen: The 17O-NMR. chemical shifts of the enriched amino acids glycine, aspartic acid and glutamic acid were measured in aqueous solution as a function of pH. High magnetic fields are necessary to resolve the α, β- and α, γ-carboxyl resonances of aspartic acid and glutamic acid, respectively. The chemical shifts of acetic acid were measured for comparative reasons. Ionization constants and titration shifts were obtained by nonlinear least-squares fits to one-proton titration curves. The average excitation energy approximation is discussed in terms of the observed changes in 17O-shielding on deprotonation. No intramolecular association between the α-amino group and the α-carboxyl group in the zwitterionic form is required to explain the high-frequency shift of the carboxylate ion. Also no indication of an intramolecular association between the α-amino group and the side-chain carboxyl groups of aspartic acid or glutamic acid was found.

Notizen: Selected oligo-L-lysine carriers and a poly-L-lysine were penicilloylated with benzylpenicillin. The resulting conjugates 2-6 were studied by IR. absorption in the solid state and circular dichroism measurements in solution. The IR. data demonstrate the lack of β-structure formation even in medium-sized peptides where such structures might be expected on the basis of previous studies on differently substituted oligo-L-lysines. Considerable proportions of right-handed α -helical conformation are exhibited by the icosa-L-lysine and poly-L-lysine conjugates 5 and 6 in water and 2,2,2-trifluoroethanol. Difficulties in obtaining fully penicilloylated conjugates are not related to the extent of α-helical conformation in aqueous solution.

Notizen: 13C- and 17O-relaxation times measured in cyclic ethers, cyclic ketones, and lactones allowed the determination of the quadrupolar interaction at the O-site. Values obtained for six-membered rings can be used as standard values for ethers (χ = 13 MHz), ketones (χ = 10.5 MHz), and esters (χ = 11.5 MHz for dicoordinated and 9.5 MHz for monocoordinated O-atom). Even within a series, no correlation is found between the 17O-chemical shift and the value of quadrupolar interaction.

Notizen: Synthesis of Macrocyclic Lactams from Ketones by Ring Enlargement Reaction2-Nitroalkanon 1 was converted to the N-substituted amide 3 by condensation with acrylaldehyde followed by reductive amination. Under the analogous reaction conditions, 2-nitrocyclododecanon (4) led to 12-nitro-15-pentadecanlactam (6).

Notizen: Reaction of 3-Dimethylamino-2,2-dimethyl-2H-azirine with 6-Methyluracil; Crystal Structure of the ProductsThe reaction of 3-dimethylamino-2,2-dimethyl-2H-azirine (1) with 6-methyl-uracil (4) in 2-propanol at 80° yields the 4H-imidazoje derivative 5 as the main product. This reaction is similar to the previously reported ones with heterocyclic compounds containing the sequence NH—CO—NH—CO. In the presence of water, 5 is easily hydrolyzed to 6. The structures of 5 and 6 have been established by X-ray crystallography.

Notizen: An enantioselective synthesis of key intermediates for the synthesis of the anti-microbially active pseudomonic acids A (1), B (2) and C (3) is described. D-Ribose (4) was used as starting material.

Notizen: The thujone derived enone 1 is converted in one step to the pentacyclic compound 4. The structure of 4 was determined by X-ray diffraction analysis. The acid-catalyzed cyclopropane-ring opening of 4 and of the model compound 9 are described.

Notizen: On 1n, π* -excitation 5, 6-epoxy-2-hydroxy-5, 6-dihydro-β-ionone ((E)-4) shows the typical behaviour of a, β-unsaturated γ, δ-epoxy ketones undergoing primarily C(γ), O-cleavage of the oxiran. However, 1π, π*-excitation of (E)-4 leads to enol ether 10 which is formed by intramolecular insertion of the hydroxyl group of the ylide c.

Notizen: The intramolecular photochemical [2+ 2]-cycloaddition of N-substituted dimethacrylimides 1a and 1c, respectively, proceeds under conditions of direct irradiation (λ = 254 nm) as well as triplet photosensitization highly regioselectively yielding predominantly the «cross» bonding (head-to-tail) cycloadducts 3a and 3c, respectively, with a 3-azabicyclo [3.1.1]heptane ring system.

Notizen: The synthesis of the (±)-form of the marine sesquiterpene (-)-Δ9(12)-capnellene (1) by double application of the a-alkynone cyclization is described. Starting with 2, 2, 5-trim ethylcyclopentanone (2), the elaboration of the tricyclo [6.3.0.02,6]undecane C-skeleton of 1 proceeded through the a-alkynone 3, which was cyclized thermally to the bicyclo [3.3.0]octenone 4. For the anellation of the third five-membered ring, 4 was transformed into the a-alkynone 5 and the latter cyclized thermally to a mixture of the angular triquinenone 6 and the linear triquinenone 7. The last steps in the synthesis of (±)-Δ9(12)-capnellene (1) were then accomplished from 7 by known methods.

Notizen: The solvolysis products of the stereoisomeric 6-cyano-2-norbornyl p-toluene sulfonates 1-4 (R = CN) in dioxane/water 7 : 3 have been determined. In contrast to an earlier report the 6exo-cyano-2exo-norbornyl p-toluenesulfonate (1; R=CN) yields 30% of the 2endo-alcohol 9 (R=CN) beside the 2exo-alcohol 10 and the norbornenes 12 and 13. The results confirm that - I substituents at C(6) reduce 1,3-bridging in the intermediate norbornyl cation and hence its rate of rearrangement. The relatively high rate constants for some 6-fluoro- and 6-cyano-2exo norbornyl p-toluenesulfonates are ascribed to C, C-hyperconjugation assisted by the conjugative effects of the 6-fluoro and cyano substituents.

Notizen: The preparation of unbranched 4-alkylbenzaldehydes free of positional and branched-chain isomers by different methods is described. A one-step preparation of the aldehydes is reported which involves the -direct hydrogenation of a Friedel Craft's complex in the presence of Pd/C catalyst.

Notizen: A further synthetic approach to 2, 5-trimethylenenorbornane (1; tricycle [5.3.0.03,9]decane, 4-homotwistbrendane), a member of the «adamantaneland», is described starting from methyl 5-oxo-2endo-norbornanecarboxylate (5). The required C2-chain was introduced by a Wittig-Horner reaction and the ring closure of the trimethylene bridge achieved by an acyloin condensation.

Notizen: The radical cations of indeno [2, 1-a]indene (1), stilbene (2) and 3, 5, 3', 5'-tetramethylstilbene (3) were prepared by γ-irradiation of the neutral precursors in an electron-scavenging matrix at 77 K. Their electronic spectra were recorded and compared to the photoelectron spectra (PE.) of the neutral precursors. The results show that either the fourth or the fifth excited doublet state of the cations is of «Non-Koopmans» type, with specific doublet energy (D) D (2Bg)=2.74 eV (1+), =2.59 eV (2+), =2.49 eV (3+). Remarkably, 1+ possesses two electronic states in the 2.7-2.8 eV energy range: 2Au («Koopmans»-type) and 2Bg («Non -Koopmans»-type). The «SDT»-equation \documentclass{article}\pagestyle{empty}\begin{document}$ {\rm D} = \sqrt {{\rm S} \cdot {\rm T}} $\end{document} approximately connecting excited singlet (S) and triplet (T) states of a neutral alternant system with the excited doublet (D) states of its radical cation - provided e-promotion occurs For all three excited states between the same (paired) orbitals-is satisfyingly exemplified by 1: S1 = 3.92 eV and T1= 2.06 eV for 1, D4 or 5=2.74 eV for 1+.

Notizen: The homo-l, 4 adduct obtained from difluorocarbene and bicyclo [2.2.1]hepta-2, 5-diene (1) was treated successively with HCl, FSO3H and SbF5 in SO2ClF at low temperature. The protic acids underwent electrophilic addition to the cyclopropane part of 1, giving the corresponding derivatives. However, in FSO3H at - 50°, protonation of the gem-difluoro grouping also occurred to give the 2-fluoro-6-fluorosulfonylbicyclo [3.2.1]oct-2-en-3-yl cation. The reaction of 1 with SbF5 at -78° led initially to the formation of the 2-fluorobicyclo [3.2.1 ]octa-2, 6-dien-4-yl cation, which rearranged to 4-fluorotricyclo [5.1.0.05,8]oct-3-en-2-yl cation at -40°. These rearrangements are discussed in the light of those expected for C8H8F square pyramidal cations.

Notizen: Synthesis of Ketoses by Chain Elongation of 1-Deoxy-1-nitroaldoses. Nucleophilic Additions and Solvolysis of Nitro EthersA method for the preparation of chain elongated uloses based upon the base-catalyzed addition of 1-deoxy-1-nitroaldoses to aldehydes and Michael acceptors and subsequent solvolytic replacement of the nitro group by a hydroxy group is described. Thus, addition of 1, 3 and 9 to formaldehyde, followed by solvolysis gave the chain elongated ulose derivatives 2, 8 and 10 (63-76%), respectively. The configuration at the anomeric center of the addition products was deduced from 13C-NMR. spectra and mutarotation. In the case of 3, the primary addition products 4 and 6 were isolated and acetylated to 5 and 7. The nitro derivatives 4-7 do not follow Hudson's rule of isorotation. Addition of 1 to benzaldehyde (44%) and to nonanal (74%) preceded with a small degree of diastereoselectivity to give 15a/15b, and 11/12, respectively. The configuration of the secondary hydroxyl group of 12 was determined by correlation with methyl 2-hydroxydecanoate (14). Addition of 1 to the galacroaldehyde 16 gave a single compound 17 (78%). The structure of this dodecosulose was determined by X-ray crystallography. Solvolysis of the acetylation product 18 in formamide gave the hemiacetal 19 (69%). Michael addition of 1 to acrylonitrile, methyl vinyl ketone and cyclohexenone under solvolytic conditions gave the hemiacetals 27, 30 and 31a,b (49%, 71% and 76%, respectively). Under non-solvolytic conditions (Bu4NF), 1 reacted with acrylonitrile, and crotononitrile to give the anomeric nitro ethers 23 and 24 (67%) and 25 and 26 (84%). respectively. Similarly. 3 added to acrylonitrile to give 28 and 29 (55%, 4:1). This reaction appears to proceed under kinetic control. Addition of 1 to ethyl propiolate and solvolysis yielded the unsaturated spirolactone 32 (50%) and the hemiacetal 33 (17%). Hydrogenation of 32 gave the saturated spirolactone 34 (100%) which was also obtained from 1 and methyl acrylate (63%). Addition of 1 to dimethylmaleate gave the unsaturated ester 35 (48%).

Notizen: Several morphinanone agonists differently substituted at C(3), C(4), C(5) and C (14) and antagonists of the 4-hydroxy and 3, 4-dimethoxy series were prepared by conventional chemistry. It was demonstrated that the oxygenation pattern in the bay-area, encompassing C(3) and C(4), is important. Alkylation at C(5) or hydroxylation at C(14) lowered the potency of the compounds. The most potent agonist was found to be the N-phenethyl-substituted ketone 27, which was six times more potent than morphine in the hot-plate assay. The 3, 4-methylenedioxy-substituted ketone 9 was about 20 times less potent than its 3, 4-dimethoxy congener. An X-ray analysis of 9 and a representative agonist showed that the stereochemical features in the bay-area were similar and could not be used to explain this difference.

Notizen: A cyclic pentapeptide containing an energy donor group and an energy acceptor group within the molecule, cyclo [Trp-Sar-Sar-Lys (DNS)-Pro], was synthesized. Its conformation, complexation with metal ions, intramolecular energy transfer, and interaction with liposomes were investigated. The precursor, cyclo [Trp-Sar-Sar Lys (Z)-Pro], contained one cis-sarcosyl peptide bond and a β-turn in which the Pro-residue occupied the 3rd position. This cyclic pentapeptide formed a complex selectively with Ba2+ and its binding constant in 95% aqueous methanol solution was 2.0 × 103 1 · mol-1. The intramolecular energy-transfer efficiency of cyclo [Trp-Sar-Sar-Lys (DNS)-Pro] was almost constant between - 60° and 40° in ethanol, while it increased at temperatures lower than 34° in liposomes as a result of the pre-transition of the lipid assembly. On the other hand, the intramolecular energy transfer efficiency of cyclo [Trp-Sar-Sar-Lys (DNS)-Pro] decreased upon complexation with Ba2+.

Notizen: The water relaxation rates of several flavoproteins in the semiquinone state have been investigated by the spin echo technique. The results indicate a rather unspecific interaction between water and the protein-bound flavosemiquinones. An average interaction distance of 0.3-0.5 nm has been estimated. From the temperature dependence of the rate constants the free energy of activation for proton exchange is calculated to be about 17 kJ/mol. The rate of proton exchange is around 1011 s-1 for the flavosemiquinones investigated are accessible to water regardless of their ionic state.The large difference in relaxation rates of water protons between D- and L- amino-acid oxidases is noticeable. Oxynitrilase exhibits the highest whereas Azotobacter vinelandii flavodoxin shows the lowest water relaxation rate of the flavoproteins studied. The results are discussed in relation to the visible-light absorption properties of the flavoproteins.

Notizen: Anhydrous solutions of Eu(ClO4)3 and Eu (NO3)3 0.05m in N, N-dimethyl formamide (DMF) are investigated by means of conductometric measurements, vibrational spectroscopy, electronic absorption and emission spectra, and fluorescence lifetime determinations. Eu (ClO4)3 is completely dissociated and no inner-sphere interaction takes place between ClO4 and Eu3+ ions. The solvated species Eu (DMF)x3+ has a C2v-symmetry and x is probably equal to 8.A more complicated situation occurs for Eu (NO3)3, the solutions of which contain at least three different solvates; the predominant species is [Eu (NO3)2 (DMF)x-4]+ (≈80% of the total Eu-concentration) and it is more stable than the mononitrato complex [Eu (NO3) (DMF) X-2]2+; the neutral complex Eu (NO3)3 (DMF) x-6 is also present, as can be inferred from a high-resolution analysis of the 5D0→7F0 emission band. The absence of emission from the excited 5D1-level can be rationalized in terms of an efficient non-radiative deexcitation path through a vibrational mode of the DMF-molecules bonded to the central metal ion.

Notizen: The acetylene → carbene rearrangement of three model a-alkynones, namely propynal (1a), 2-butynal (1b) and butynone (1c) is studied by ab initio double-zeta, double-zeta plus polarization and double-zeta plus self-consistent electron pairs calculations. Transition states are located by force-gradient geometry optimization. Calculated minimum energy reaction paths reveal substituent effects on the activation parameters, which indicate that a H-atom or an alkyl group competes favorably with an acyl group in the [1,2]-shift from a-alkynones 1 to the corresponding acylvinylidenes 5.

Notizen: The 103Rh-resonance has been investigated at 2.8 MHz in mono- and dinuclear olefin complexes by steady-state NMR.-pulse techniques. For dirhodium complexes with scalar Rh, Rh-coupling, a selective rf-irradiation was applied to improve sensitivity. Within the same measuring time the signal/noise ratio is improved by the factor (T2/T2*)1/2 by this steady-state method in comparison with the usual free-induction technique. (T1/T2)-ratios, as obtained from the dependence of signal in tensity on the pulse-flip angle are discussed in terms of relaxation mechanisms and chemical exchange phenomena. From (T1/T2)- and (T1 + T2)-experiments, individual T1 and T2 values have been determined for C5H5RhC8H12 and Rh(acac)3.The 103Rh-chemical shifts of 39 olefin complexes are reported. Shielding depends upon the (formal) oxidation state of Rh whereby resonances of pure olefin complexes appear at the low-frequency end of the δ-scale, which extends over 10000 ppm. For cyclic 1,3-diene ligands Rh-shielding increases with decreasing ring size and decreases with further conjugation of the diene systems.In the dirhodium complexes, Rh, Rh spin-coupling constants are 〈 10 Hz. Rh, C-coupling constants in (diene)RhCp-complexes increase, for the terminal diene C-at om, with increasing ring size of the 1,3-diene, 1J(Rh, C) = 11.7 to 17.4 Hz.

Notizen: Fulvene-Dieters: Synthesis, Structure Elucidation and Thermal BehaviourIn contrast to earlier assumptions, thermal reaction of pure fulvene (1a), 6-methylfulvene (lb) and 6, 6-dimethylfuivene (1c) at 227deg; gives oligomeric mixtures consisting mainly of the endo-[4 + 2]-eycloaddition products 2a, 2b and 2c. Thermal reactivity of the fulvenes decreases strongly in the series 1a 〉 1b 〉 1c. While the dimers 2b and 2c equilibrate very easily in solution above room temperature with 1b and 1c, respectively, 2a equilibrates with the isomer 5a (—1, 6-Dimethyliden3a α, 3bβ, 6a α, 6bβ-tetrahydro-1-H), 6 H-bi (cyclopentadienylen). This surprising rearrangement envolves a formal 1,3-shift of the 1, 2-dihydrofulvene-unit of 2a (s. Scheme 4).