Ligands ligand optimisation

Enantioselective reduction of acetophenone was achieved in a ruthenium-catalysed hydrogen transfer reaction using isopropanol as the hydrogen source in the presence of mono-tosylated (R, R)-diphenylethylenediamine, ephedrine or norephedrine as chiral auxiliary ligands. Under optimised conditions, ( R)-l-phenylethanol was obtained in 90% yield and 82% enantiomeric excess (ee) within 9 min. f-Butylphenylketone was reduced under similar conditions in almost quantitative yield but in moderate ee... 

Further tuning the ligands and optimising the resulting chelated aluminium alkoxides, for example by increasing the size of the chelates and the number of coordination sites as found in aluminium porphyrins, also leads... 

A series of mono- and dialkylated, chiral 1,2-amino-phosphinamide ligands (752) have been successfully applied in the chiral phosphinamide-Zn(ii) catalysed asymmetric Henry reaction between benzaldehyde and nitromethane (Scheme 210). The effects of the N-substituent sizes of chiral ligands (752) on the enantioselectivities in this reaction have been correlated using a predictive quantitative structure-activity relationship (QSAR) mathematical model. A quantitative correlation model has been also established based on subtractive Sterimol parameters. Ligand optimisation based on the QSAR model led to chiral 1,2-amino-phosphinamide ligand (752a), which produced (R)-p-nitroalcohol (753) in excellent yield (99%) and enantioselectivity (92% ee). ... 

New catalysts were prepared after optimisation of the Ugand structure. The most efficient organo catalyst for this reaction was an amido-thiourea derivative (Scheme 43). Interestingly, dissymmetrical ligands were more efficient and selective for this reaction. 

The abundance of structural information has led to a significant increase in the use of structure-based methods both to identify and to optimise inhibitors of protein kinases. The focus to date has centred upon small molecule ATP-competitive inhibitors and there are numerous examples of protein-ligand complexes available to guide design strategies. ATP binds in the cleft formed between the N- and C-terminal lobes of the protein kinase, forming several key interactions conserved across the protein kinase family. The adenine moiety lies in a hydrophobic region between the jS-sheet structure of subdomains I and II and residues from subdomains V and VIb. A... 

GOLD Genetic Optimisation of Ligand Docking CCDC WWW. cede. cam. ac.uk... 

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