Enantioselective synthesis of DIANANE, a novel C2-symmetric chiral diamine for asymmetric catalysis

DIANANE (endo,endo-2,5-diaminonorbornane) is a novel chiral C(2)-symmetric diamine, based on the rigid bicyclo[2.2.1]heptane scaffold. Schiff-base ligands derived from DIANANE have already found use in asymmetric catalysis, e.g., in the highly enantioselective Nozaki-Hiyama-Kishi reaction. We herein describe a practical synthesis of enantiomerically pure DIANANE, starting from norbornadiene in four steps: (i) Pd-MOP catalyzed Hayashi-hydrosilylation/Tamao-Fleming oxidation, (ii) oxidation to norbornane-2,5-dione, (iii) endo-selective reductive amination with benzylamine, and (iv) hydrogenolytic debenzylation. None of the steps involves chromatographic purification. For the Tamao-Fleming oxidation, the use of hydrogen peroxide in the form of its urea clathrate instead of aqueous solution proved beneficial. By the above sequence, enantiomerically pure (ee >or=99%) DIANANE was obtained from norbornadiene in 40-50% overall yield. The relative and absolute configuration of DIANANE was confirmed by X-ray crystallography of the DIANANE bis-tosylamide, and of its bis-camphorsulfonamide. Furthermore, the synthesis and X-ray crystal structure of the Schiff-base ligand derived from DIANANE and 3,5-di-tert-butyl salicylic aldehyde are reported.     

Physiological loading of cartilage replacement materials in a bioreactor environment

Trying to replace injured cartilage by implants is a common practice in biomedical engineering. These implants can be non-seeded or seeded with human cartilage cells. To initiate cell multiplication and oriented cell growth in cell seeded implants, the implants are cultivated and usually stimulated electrically or mechanically in a bioreactor before implanting. In the present study, a knee testing bench combined with a bioreactor environment is developed. Doing so, it is possible to stimulate such implants controlled in a physiologically consistent, multi-dimensional way. The implants are placed in a recreated human knee joint and stimulated with several physiological load cycles of reproduced walking. After some days, the implanted material can be removed and mechanically and biologically evaluated in cooperation with the RWTH Aachen University Hospital. The new experimental set-up enables us for the first time to study the remodelling effect, the efficiency of the preconditioning as well as the influence of the body-conformable load on the material. Furthermore, the need of cell colonisation in the implants shall be investigated. To understand the correlation between tissue remodelling and mechanical load history, the experiment is also numerically investigated, based on a geometrically realistic FE model of the recreated human knee and appropriate material models for the involved structures. Doing so, the strains and stresses, as well as the shear forces in the implant can be evaluated. The results will be compared to experimental data. (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim)     

The Yamabe Constant on Noncompact Manifolds

We prove several facts about the Yamabe constant of Riemannian metrics on general noncompact manifolds and about S. Kim’s closely related “Yamabe constant at infinity”. In particular, we show that the Yamabe constant depends continuously on the Riemannian metric with respect to the fine C ²-topology, and that the Yamabe constant at infinity is even locally constant with respect to this topology. We also discuss to what extent the Yamabe constant is continuous with respect to coarser topologies on the space of Riemannian metrics.