Total and Semi‐Syntheses of Antimicrobial Thuggacin Derivatives

The total and semi‐synthesis of 13 new macrolactones derived from thuggacin, which is a secondary metabolite from the myxobacterium Sorangium cellulosum, are reported. The thuggacins have attracted much attention due to their strong antibacterial activity, particularly towards Mycobacterium tuberculosis. This study focuses on 1) thuggacin derivatives that cannot equilibrate by transacylation between the three natural thuggacins A–C, 2) the roles of the thiazole ring, and 3) the hexyl side chain at C2. Semi‐synthetic O‐methylation at C17 suppressed the transacylations without a substantial loss of antibacterial activity. Exchanging the C17–C25 side chain for simplified hydrophobic chains led to complete loss of antibacterial activity. Exchange of the thiazole by an oxazole ring or removal of the hexyl side chain at C2 had no substantial effect on the biological properties.     

Columnar Liquid‐Crystalline Dinaphthoperylenetetracarboxdiimides

Although the double Friedel–Crafts acylation of arenes with ethyl chloroglyoxylate is hindered by the strongly deactivating effect of the first‐entering glyoxylic substituent, the double reaction is successful with the reactive arene perylene under long reaction times and with concomitant ester hydrolysis. The reaction is regiospecific, giving the 3,9‐regioisomer exclusively. This perylenylenediglyoxylic acid is condensed first with o‐bromophenylacetic acid and then with α‐branched alkylamines to yield the title compounds. Whilst the corresponding tetraalkyl esters only show monotropic mesophases, these diimides show enantiotropic columnar mesophases that can be maintained at room temperature if racemically branched alkyl chains of moderate size are used. A palladium‐induced C?C bond migration during the build‐up of the arene system leads to an isomeric side product of reduced symmetry that can be isolated by aggregation‐controlled chromatographic separation. The HOMO and LUMO energies of the title compounds are considerably higher than those of established perylenetetracarboxdiimides.     

Studies on pre-hump and main fractions of cellulose-2,5-acetate in acetone

Technical cellulose-2.5-acetates (CA 2.5) were characterized regarding their carbohydrate composition in comparison to the raw material. The association of the CA 2.5 samples in acetone was studied by size exclusion chromatography (SEC) using various acetone grades and styrene divinylbenzene copolymer columns. In HPLC grade acetone with and without addition of 1% water up to three different pre-humps eluted in front of the main fraction of the polymer. The evaluation of the main peak by light scattering measurements resulted in high molar masses indicating that for these technical CA 2.5 samples even the main fraction is not dissolved without association. No pre-humps or association phenomena were observed after addition of 1 ppm LiBr to HPLC grade acetone or with p.a. grade acetone. In addition pre-hump enriched and pre-hump free fractions were isolated by fractionated precipitation. The carbohydrate composition of these fractions was determined and correlated with their association pattern in SEC investigations.     

Gasphasen-Reaktionen. 92. Thermische HCl-Abspaltung aus Alkyldichlorphosphanen (H3C/H)3C?PCl2 zu Phosphaalkenen (H3C/H)2CPCl und Phosphaalkinen (H3C/H)C≡P

Gasphase Reactions. 92 Thermal Elimination of HCl from Alkyldichlorophosphanes (H₃C/H)₃C? PCl₂ to Phosphaalkenes (H₃C/H)₂C?PCl and Phosphaalkines (H₃C/H)C≡P The alkyldichlorophosphanes H₃C? PCl₂, ClH₂? PCl₂, (H₃C)H₂C? PCl₂ and (H₃C)₂HC? PCl₂ split off HCl on heating in a gasflow under reduced pressure. PE spectroscopic gas analysis proves that under these conditions the short-lived phosphaalkenes H₂C?PCl, (H₃C)H₂C?PCl and – catalyzed by [MgCl₂? MgO/SiO₂]_∞ – (H₃C)₂C?PCl as well as the phosphaalkines HC≡P and (H₃C)C≡P are formed, all of which can be isolated by low temperature condensation. Based on the PES ionization patterns recorded and on the MNDO calculations for their assignment, the π_CP multiple bonds are discussed. The presumable pathway of the HCl elimination is rationalized for (H₃C)H₂C? PCl₂ by an approximate MNDO energy hypersurface.     

Structure–Function Relationships of New Lipids Designed for DNA Transfection

Cationic liposome/DNA complexes can be used as nonviral vectors for direct delivery of DNA‐based biopharmaceuticals to damaged cells and tissues. To obtain more effective and safer liposome‐based gene transfection systems, two cationic lipids with identical head groups but different chain structures are investigated with respect to their in vitro gene‐transfer activity, their cell‐damaging characteristics, and their physicochemical properties. The gene‐transfer activities of the two lipids are very different. Differential scanning calorimetry and synchrotron small‐ and wide‐angle X‐ray scattering give valuable structural insight. A subgel‐like structure with high packing density and high phase‐transition temperature from gel to liquid‐crystalline state are found for lipid 7 (N′‐2‐[(2,6‐diamino‐1‐oxohexyl)amino]ethyl‐2,N‐bis(hexadecyl)propanediamide) containing two saturated chains. Additionally, an ordered head‐group lattice based on formation of a hydrogen‐bond network is present. In contrast, lipid 8 (N′‐2‐[(2,6‐diamino‐1‐oxohexyl)amino]ethyl‐2‐hexadecyl‐N‐[(9Z)‐octadec‐9‐enyl]propanediamide) with one unsaturated and one saturated chain shows a lower phase‐transition temperature and a reduced packing density. These properties enhance incorporation of the helper lipid cholesterol needed for gene transfection. Both lipids, either pure or in mixtures with cholesterol, form lamellar phases, which are preserved after addition of DNA. However, the system separates into phases containing DNA and phases without DNA. On increasing the temperature, DNA is released and only a lipid phase without intercalated DNA strands is observed. The conversion temperatures are very different in the two systems studied. The important parameter seems to be the charge density of the lipid membranes, which is a result of different solubility of cholesterol in the two lipid membranes. Therefore, different binding affinities of the DNA to the lipid mixtures are achieved.