A new approach towards peptidosulfonamides: synthesis of potential inhibitors of bacterial peptidoglycan biosynthesis enzymes MurD and MurE

Peptidosulfonamides are an emerging group of peptidomimetics with a variety of applications in medicinal chemistry. We present a novel approach to the synthesis of peptidosulfonamides, and apply it to a series of new potential inhibitors of the bacterial peptidoglycan biosynthesis enzymes MurD and MurE. The synthesis was conducted via N-phthalimido β-aminoethanesulfonyl chlorides, which are new building blocks for the synthesis of peptidosulfonamides. In the most crucial step, sulfonic acids or their sodium salts were converted into the corresponding sulfonyl chlorides using an excess of either SOCl₂ or SOCl₂/DMF, and then coupled to the C-protected amino acid. None of the compounds significantly inhibited MurD, however, some inhibited MurE; one had an IC₅₀ below 200 μM, which constitutes a promising starting point for further development. Molecular modelling simulations were performed on two analogues to investigate the absence of inhibitory activity of the sulfonamide compounds on MurD.     

A Ramsey‐type result for the hypercube

We prove that for every fixed k and ? ≥ 5 and for sufficiently large n, every edge coloring of the hypercube Q_n with k colors contains a monochromatic cycle of length 2 ?. This answers an open question of Chung. Our techniques provide also a characterization of all subgraphs H of the hypercube which are Ramsey, that is, have the property that for every k, any k‐edge coloring of a sufficiently large Q_n contains a monochromatic copy of H. © 2006 Wiley Periodicals, Inc. J Graph Theory 53: 196–208, 2006     

Mappings of finite distortion: Hausdorff measure of zero sets

We prove that a for a mapping f of finite distortion , the -Hausdorff measure of any point preimage is zero provided is integrable, with , and the multiplicity function of f is essentially bounded. As a consequence for we obtain that the mapping is then open and discrete. Received: 18 June 2001 / Revised version: 31 January 2002 / Published online: 27 June 2002     

Flat Information Geometries in Black Hole Thermodynamics

The Hessian of either the entropy or the energy function can be regarded as a metric on a Gibbs surface. For two parameter families of asymptotically flat black holes in arbitrary dimension one or the other of these metrics are flat, and the state space is a flat wedge. The mathematical reason for this is traced back to the scale invariance of the Einstein–Maxwell equations. The picture of state space that we obtain makes some properties such as the occurence of divergent specific heats transparent.Supported by VR.     

On uniformly Gâteaux smooth norms and normal structure

It is shown that every separable Banach space admits an equivalent norm that is uniformly Gâteaux smooth and yet lacks asymptotic normal structure.

     

6-Thia-1-aza-5λ5-phosphabicyclo[3.2.0]hept-3-ene und Isothiocyanatophosphin-sulfide aus (Methylidenamino)phosphinen,Schwefelkohlenstoff und Acetylen- oder Ethylen-Derivaten

6-Thia-l-aza-5λ⁵-phosphabicyclo[3.2.0]hept-3-enes and Isothiocyanatophosphine-sulfides from (Methylidenamino)phosphines, Carbon Disulfide, and Acetylene- or Ethylene Derivatives (Methylidenamino)phosphines react with carbon disulfide to 1,3,2-thiazaphosphete derivatives 2 . Acetylenedicarboxylates give with 2 6-thia-l-aza-5λ⁵-phosphabicyclo[3.2.0]hept-3-enes 4a , b , and acrylates yield isothio-cyanatophosphin-sulfides 5a – c . The structures of 4a and 5a are proven by an X-ray diffraction analysis.