Novel chimeric scaffolds to extend the exploration of receptor space: hybrid beta-D-glucose-benzoheterodiazepine structures for broad screening. Effect of amide alkylation on the course of cyclization reactions

New molecular platforms which are hybrids of two scaffolds-namely, beta-d-glucose and benzodiazepine, each able to bind several proteins-were designed, synthesized and functionalized to serve as probes for broad biological screening. Herein, we describe the syntheses and chemical properties of these novel chimeric scaffolds. Attempted cyclization of the functionalized analogues (-)-96 and (-)-97 afforded the corresponding dimers (-)-98 and (-)-99, respectively, under a variety of reaction conditions, even at concentrations of only 0.001 N. Consideration of factors affecting the conformation of amide bonds and their effects on cyclization reactions led us to alkylate the amide bond. As expected, the cyclization of the N-methyl derivative (-)-110 afforded exclusively the unimolecular cyclization product (+)-111. These compounds are only now undergoing broad screening and represent therefore at present a "prospecting library."     

Preparation and relevance of a cross-coupling product between sinapyl alcohol and sinapyl p-hydroxybenzoate

Cross-coupling of sinapyl p-hydroxybenzoate and sinapyl alcohol produces an 8-8-cross-coupled product that is also detected in lignifying poplar tissues, implicating sinapyl p-hydroxybenzoate as a lignin precursor.     

Cryoprobe 3D NMR of acetylated ball-milled pine cell walls

3D NMR of solubilized ball-milled pine cell walls reveals striking details of lignin units, right down to differentiating stereoisomers in the polymer. Such 3D spectral editing therefore overcomes the need to isolate wall components to study their structures.     

Convergence of automorphisms of compact projective planes

We show that a pointwise convergent sequence ( _n) _nN of continuous collineations of a compact projective plane converges uniformly if and only if the pointwise limit of ( _n) _nN has a quadrangle in its image. Moreover is then a continuous collineation. Furthermore, we derive that a homomorphism between topological projective planes is continuous if and only if it is continuous at some point.Supported by DFG/Graduiertenkolleg.     

Magnetic susceptibility of the TaV2/H2 system

The magnetic susceptibility exhibited by the ordered (C-15) and random bcc allotropes of TaV₂ decreases linearly with increasing hydrogen content. However, the susceptibility exhibited by the (C-15) form is about four times more sensitive to hydrogen than that exhibited by the bcc form. The results are in qualitative accord with the thermodynamics of hydrogen solution.     

An interactive weighted Tchebycheff procedure for multiple objective programming

The procedure samples the efficient set by computing the nondominated criterion vector that is closest to an ideal criterion vector according to a randomly weighted Tchebycheff metric. Using ‘filtering’ techniques, maximally dispersed representatives of smaller and smaller subsets of the set of nondominated criterion vectors are presented at each iteration. The procedure has the advantage that it can converge to non-extreme final solutions. Especially suitable for multiple objective linear programming, the procedure is also applicable to integer and nonlinear multiple objective programs.     

Unconvential construction of a substituted benzene ring

A substituted biphenyl suitable for elaboration to the antibiotic resistomycin ($\text{1}$) has been synthesised by a novel double Michael process involving dimethyl β-oxoglutarate and the diacetylenic diester ($\text{4}$).