Chiral complexes, drugs, ligands

There is currently a growing awareness amongst pharmacologists of the importance of stereochemistry, particularly of the chirality of drug molecules. These drugs may be coordination complexes, ligand molecules with potential for in vivo coordination, or molecules whose in vivo interactions are unknown. 

The trans- 1,2-cyclohexanediamine used in this complex also has been used in a variety of chiral reagents and ligands for asymmetrical cyclopropanation, alkylation, di-hydroxylation, and such95). Merck and Sepracor have developed a drug synthesis based on such a system (10.44).96... 

ID-ROESY studies on the complexes of the chiral antihistaminic drug dimethindene (DM) with native P-CD and TM-P-CD do not detect the significant differences in the structure of the ligand-CD complexes. Benzimidazole moiety of the molecule is included in the cavity of both CDs entering from the secondary side. In spite of the structural similarity of these two complexes the opposite chiral recognition pattern was observed in CE. In addition, the ID-ROESY data for the dimethindene-P-CD complex do not confirm a partial inclusion of the pyridine moiety of DM into the cavity of p-CD which has been suggested based on the CICS data [28]. 

Platinum complexes with chiral phosphorus ligands have been extensively used in asymmetric hydroformylation. In most cases, styrene has been used as the substrate to evaluate the efficiency of the catalyst systems. In addition, styrere was of interest as a model intermediate in the synthesis of arylpropionic acids, a family of anti-inflammatory drugs.308,309 Until 1993 the best enantio-selectivities in asymmetric hydroformylation were provided by platinum complexes, although the activities and regioselectivities were, in many cases, far from the obtained for rhodium catalysts. A report on asymmetric carbonylation was published in 1993.310 Two reviews dedicated to asymmetric hydroformylation, which appeared in 1995, include the most important studies and results on platinum-catalogued asymmetric hydroformylation.80,81 A report appeared in 1999 about hydrocarbonylation of carbon-carbon double bonds catalyzed by Ptn complexes, including a proposal for a mechanism for this process.311... 

The reaction can be carried out asymmetrically, using nickel complexes of chiral phosphite ligands. Examples are the enantioselective hydrocyanation of norbomene using ligand (22-XVIII),48 and of vinylnaphthalene derivatives with (22-XIX).49 The latter is a precursor for the anti-inflammatory drug naproxen. 

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