Regio- and Stereoselective 1,2-Carboboration of Ynamides with Aryldichloroboranes.

AbstractCatalyst‐free 1,2‐carboboration of ynamides is presented. Readily available aryldichloroboranes react with alkyl‐ or aryl‐substituted ynamides in high yields with complete regio‐ and stereoselectivity to valuable β‐boryl‐β‐alkyl/aryl α‐aryl substituted enamides which belong to the class of trisubstituted alkenylboronates. The 1,2‐carboboration reaction is experimentally easy to conduct, shows high functional group tolerance and broad substrate scope. Gram‐scale reactions and diverse synthetic transformations convincingly demonstrate the synthetic potential of this method. The reaction can also be used to access 1‐boraphenalenes, a class of boron‐doped polycyclic aromatic hydrocarbons

Inverting Small Molecule-Protein Recognition by the Fluorine Gauche Effect: Selectivity Regulated by Multiple H→F Bioisosterism

Fluorinated motifs have a venerable history in drug discovery, but as C(sp3 )@F-rich 3D scaffolds appear with increasing frequency, the effect of multiple bioisosteric changes on molecular recognition requires elucidation. Herein we demonstrate that installation of a 1,3,5-stereotriad, in the substrate for a commonly used lipase from Pseudomonas fluorescens does not inhibit recognition, but inverts stereoselectivity. This provides facile access to optically active, stereochemically well-defined organofluorine compounds (up to 98% ee). Whilst orthogonal recognition is observed with fluorine, the trend does not hold for the corresponding chlorinated substrates or mixed halogens. This phenomenon can be placed on a structural basis by considering the stereoelectronic gauche effect inherent to F@C@C@X systems (s!s*). Docking reveals that this change in selectivity (H versus F) with a common lipase results from inversion in the orientation of the bound substrate being processed as a consequence of conformation. This contrasts with the stereochemical interpretation of the biogenetic isoprene rule, whereby product divergence from a common starting material is also a consequence of conformation, albeit enforced by two discrete enzymes

Metabolic Engineering of Saccharomyces cerevisiae for Production of Novel Cyanophycins with an Extended Range of Constituent Amino Acids▿

Cyanophycin (multi-l-arginyl-poly-l-aspartic acid; also known as cyanophycin grana peptide [CGP]) is a putative precursor for numerous biodegradable technically used chemicals. Therefore, the biosynthesis and production of the polymer in recombinant organisms is of special interest. The synthesis of cyanophycin derivatives consisting of a wider range of constituents would broaden the applications of this polymer. We applied recombinant Saccharomyces cerevisiae strains defective in arginine metabolism and expressing the cyanophycin synthetase of Synechocystis sp. strain PCC 6308 in order to synthesize CGP with citrulline and ornithine as constituents. Strains defective in arginine degradation (Car1 and Car2) accumulated up to 4% (wt/wt) CGP, whereas strains defective in arginine synthesis (Arg1, Arg3, and Arg4) accumulated up to 15.3% (wt/wt) of CGP, which is more than twofold higher than the previously content reported in yeast and the highest content ever reported in eukaryotes. Characterization of the isolated polymers by different analytical methods indicated that CGP synthesized by strain Arg1 (with argininosuccinate synthetase deleted) consisted of up to 20 mol% of citrulline, whereas CGP from strain Arg3 (with ornithine carbamoyltransferase deleted) consisted of up to 8 mol% of ornithine, and CGP isolated from strain Arg4 (with argininosuccinate lyase deleted) consisted of up to 16 mol% lysine. Cultivation experiments indicated that the incorporation of citrulline or ornithine is enhanced by the addition of low amounts of arginine (2 mM) and also by the addition of ornithine or citrulline (10 to 40 mM), respectively, to the medium

Løslatt og hjemløs

En stor andel innsatte i norske fengsler løslates uten å ha en bolig. Hvor mange dette har dreid seg om var ikke tallfestet. Målet med prosjektet Boligsituasjonen og bostedsløshet etter fengselsopphold har blant annet vært å undersøke hvor mange som har egen bolig ved løslatelsen og hvilke andre boformer eller alternativer innsatte blir løslatt til. Prosjektet har undersøkt om den innsatte, fengselet og sosialtjenesten i den innsattes hjemkommune samarbeider for å løse den innsattes boligproblem og studert hvordan dette samarbeidet foregår. Rapport gir også et bilde av hvordan enkelte faktorer virker for og mot boligetablering etter fengselsopphold. Tilknyttet prosjekt Bolig etter sonin