Neue β-Lactam-Antibiotika. Zur Funktionalisierung von 3-Hydroxy-3-cephem-4-carbonsäureestern durch die Wittig-Reaktion. Modifikationen von Antibiotika. 16. Mitteilung [1]

New β-lactam antibiotics. Functionalisation of 3-hydroxy-3-cephem-4-carboxylic esters through the Wittig reaction The 3-hydroxy-ceph-3-em-esters 1a, b reacted smoothly with stabilized phosphor-ylids to give a series of derivatives which were converted into the microbiologically active acids 14a, c, 15c and 20 by known procedures. The synthesis of the amides 23, 24, 26 and of the ester 28 from the 3-carboxymethyl-derivative 19 is also reported.     

N-Haloamidines-V: Reaction of N-chloro-N'-aroyl-acetamidines and -benzamidines with enamines

The reaction between N-chloro-N'-aroyl-amidines and β,β-disubstituted enamines affords 1 - aroyl - 4 -amino - 4,5 - dihydro - imidazoles in low yields, the main reaction product being N - (2 - morpholino - 2,2 -disubstituted) - ethylidene - N' - aroyl - amidines. A similar reaction course was not observed with enamines bearing a hydrogen atom in the β-position. In this case only products derived from electrophilic chlorination on enamines were isolated.     

Synthesis of 4,5-dihydro-2,4-benzoxazepin-3( 1H)ones and 1,3,4,5-tetrahydro-2,4-benzoxazepines

o- Aminomethylbeiizyl alcohols (X) easily cyclize with phosgene in an aqueous alkaline medium to form 4,5-dihydro-2,4-benzoxazepin-3(1H)ones (IV) and with aldehydes in acidic conditions to yield 1,3,4,5-tetrahydro-2,4-benzoxazepines (V). The characteristics and chemical behaviour of these new heterocyclic ring systems are reported.     

Effect of ortho-SR groups on O-H bond strength and H-atom donating ability of phenols: a possible role for the Tyr-Cys link in galactose oxidase active site?

Rotation about the Ar-S bond in ortho-(alkylthio)phenols strongly affects the bond dissociation enthalpy (BDE) and the reactivity of the OH group. Newly synthesized sulfur containing heterocycles 3 and 4, where the -SR group is almost coplanar with the phenolic ring, are characterized by unusually low BDE(O-H) values (79.6 and 79.2 kcal/mol, respectively) and by much higher reactivities toward peroxyl radicals than the ortho-methylthio derivative 1 (82.0 kcal/mol). The importance of the intramolecular hydrogen bond (IHB) in determining the BDE(O-H) was demonstrated by FT-IR experiments, which showed that in heterocycles 3 and 4 the IHB between the phenolic OH group and the S atom is much weaker than that present in 1. Since the IHB can be formed only if the -SR group adopts an out-of-plane geometry, this interaction is possible only in the methylthio derivative 1 and not in 3 and 4. The additive contribution to the phenolic BDE(O-H) of the -SR substituent therefore varies from -3.1 to +2.8 kcal/mol for the in-plane and out-of-plane conformations, respectively. These results may be relevant to understanding the role of the tyrosine-cysteine link in the active site of galactose oxidase, an important enzyme that catalyzes the two-electron aerobic oxidation of primary alcohols to aldehydes. The switching of the ortho -SR substituent between perpendicular and planar conformations may account for the catalytic efficiency of this enzyme.     

Directed synthesis of noncentrosymmetric molybdates using composition space analysis

A systematic investigation of the factors governing the reaction product composition, hydrogen bonding, and symmetry was conducted in the MoO3/3-aminoquinuclidine/H2O system. Composition space analysis was performed through 36 individual reactions under mild hydrothermal conditions using racemic 3-aminoquinuclidine. Single crystals of three new compounds, [C7H16N2][Mo3O10] x H2O, [C7H16N2]2[Mo8O26] x H2O, and [C7H16N2]2[Mo8O26] x 4 H2O, were grown. The relative phase stabilities for these products are dependent upon the reactant mole fractions in the initial reaction gel. This phase stability information was used to direct the synthesis of two new noncentrosymmetric compounds, using either (S)-(-)-3-aminoquinuclidine dihydrochloride or (R)-(+)-3-aminoquinuclidine dihydrochloride. [(R)-C7H16N2]2[Mo8O26] and [(S)-C7H16N2]2[Mo8O26] both crystallize in the noncentrosymmetric space group P2(1) (No. 4), which has the polar crystal class 2 (C2). The second-harmonic generation activities were measured on sieved powders. The structure-directing properties of the molybdate components in each compound were determined using bond valence sums. The structures of all five compounds were determined using single-crystal X-ray diffraction.     

Thioether sulfur oxygenation from O2 or H2O2 reactivity of copper complexes with tridentate N2Sthioether ligands

To model thioether-copper coordination chemistry including oxidative reactivity, such as occurs in the copper monooxygenases peptidylglycine -hydroxylating monooxygenase (PHM) and dopamine beta-hydroxylase (DbetaH), we have synthesized new tridentate N2S ligands LSEP and LSBz [LSEP = methyl(2-phenethylsulfanylpropyl)(2-pyridin-2-ylethyl)amine; LSBz = (2-benzylsulfanylpropyl)methyl(2-pyridin-2-ylethyl)amine)]. Both copper(I) and copper(II) complexes have been prepared, and their respective O2 and H2O2 chemistry has been studied. Under mild conditions, oxygenation of [(LSEP)CuI]+ (1a) and [(LSBz)CuI]+ (2a) leads to ligand sulfoxidation, thus exhibiting copper monooxygenase activity. A copper(II) complex of this sulfoxide ligand product, [(LSOEP)CuII(CH3OH)(OClO3)2], has been structurally characterized, demonstrating Cu-Osulfoxide ligation. The X-ray structure of [(LSEP)CuII(H2O)(OClO3)]+ (1b) and its solution UV-visible spectral properties [S-CuII LMCT band at 365 nm (MeCN solvent); epsilon = 4285 M-1 cm-1] indicate the thioether sulfur atom is bound to the cupric ion in both the solid (CuII-S distance: 2.31 A) and solution states. Reaction of 1b with H2O2 leads to sulfonation via the sulfoxide; excess hydrogen peroxide gives mostly sulfone product. These results may provide some insight into recent reports concerning protein methionine oxidation, showing the potential importance of copper-mediated oxidation processes in certain biological settings.     

Synthesis of 3-substituted 2-fluoro- and 2,2-difluoroaziridines

A new route for the synthesis of stable 3-alkyl- and 3-aryl-2(,2)-(di)fluoroaziridines was developed by hydride reduction of novel alpha-bromo- and alpha-chloro-alpha(,alpha)-(di)fluoroketimines and subsequent ring closure of beta-fluorinated beta-chloro- and beta-bromoamines. This is the first report on the synthesis of 2,2-difluoroaziridines sensu stricto.     

Comparison of thermodynamic properties of coarse-grained and atomic-level simulation models.

Thermodynamic data are often used to calibrate or test amomic-level (AL) force fields for molecular dynamics (MD) simulations. In contrast, the majority of coarse-grained (CG) force fields do not rely extensively on thermodynamic quantities. Recently, a CG force field for lipids, hydrocarbons, ions, and water, in which approximately four non-hydrogen atoms are mapped onto one interaction site, has been proposed and applied to study various aspects of lipid systems. To date, no extensive investigation of its capability to describe salvation thermodynamics has been undertaken. In the present study, a detailed picture of vaporization, solvation, and phase-partitioning thermodynamics for liquid hydrocarbons and water was obtained at CG and AL resolutions, in order to compare the two types or models and evaluate their ability to describe thermodynamic properties in the temperature range between 263 and 343 K. Both CG and AL models capture the experimental dependence of the thermodynamic properties on the temperature, albeit a systematically weaker dependence is found for the CG model. Moreover, deviations are found for solvation thermodynamics and for the corresponding enthalpy-entropy compensation for the CG model. Particularly water/oil repulsion seems to be overestimated. However, the results suggest that the thermodynamic properties considered should be reproducible by a CG model provided it is reparametrized on the basis of these liquid-phase properties.