Aircraft selection modeling: a multi-step heuristic to enumerate airlift alternatives

Annals of Operations Research - We consider the use of the new C-130J-30 aircraft for long distance (strategic) cargo movement. Currently, only large aircraft, the C-5 and the C-17, are identified...     

Directed evolution of hybrid enzymes: Evolving enantioselectivity of an achiral Rh-complex anchored to a protein

The concept of utilizing the methods of directed evolution for tuning the enantioselectivity of synthetic achiral metal-ligand centers anchored to proteins has been implemented experimentally for the first time.     

Optimized Scalable Synthesis of Chiral Iridium Pyridyl-Phosphinite (Pyridophos) Catalysts

Iridium catalysts with chiral P,N ligands have greatly enhanced the scope of asymmetric olefin hydrogenation because they do not require a coordinating group near the C=C bond like Rh and Ru catalysts. Pyridophos ligands, possessing a conformationally restricted annulated pyridine framework linked to a phosphinite group, proved to be particularly effective, inducing high enantioselectivities in the hydrogenation of a remarkably broad range of substrates. Here we report the development of an efficient scalable synthesis for the two most versatile Ir-pyridophos catalysts, derived from 2-phenyl-8-hydroxy-5,6,7,8-tetrahydroquinoline or the analogue with a five-membered carbocyclic ring, respectively, by modification and optimization of the original synthetic route. The optimized route renders both catalysts readily accessible in multi-gram quantities in analytically pure form in overall yields of 26–37 %, starting from acetophenone and cyclopentanone or cyclohexanone, respectively. A major advantage of the new synthesis is the efficient and practical kinetic resolution of the late-stage pyridyl alcohol intermediates with commercial immobilized Candida antarctica lipase B, giving access to both enantiomers of these catalysts as essentially enantiopure compounds. The catalysts are obtained as crystalline solids, which are air-stable and can be stored for years at −20 °C without notable decomposition.     

Directed evolution of enantioselective hybrid catalysts: a novel concept in asymmetric catalysis

The concept of directed evolution of enantioselective hybrid catalysts was proposed in 2001/2002 and implemented experimentally for the first time in a proof-of-concept study in 2006. The idea is based on directed evolution, which comprises repeating cycles of random gene mutagenesis/expression/screening in a Darwinistic sense for the purpose of improving the catalytic profile of enzymes. In the case of hybrid catalysts, mutagenesis/expression of a protein is first performed with formation of a library of mutants, which are then modified chemically en masse with the introduction of an appropriate achiral ligand system harboring a transition metal. Screening these mutant hybrid catalysts in a given transition metal-catalyzed reaction then leads to an improved catalyst, so that the corresponding gene can be used to start another evolutionary cycle. This process can be repeated as often as needed until the desired catalytic profile has been reached, e.g., enhanced enantioselectivity.