Enantioselective drug action

Jamali R, Mehvar, R, Pasutto RM. 1989. Enantioselective aspects of drug action and disposition therapeutic pitfalls. J Pharm Sci 78 695. 

Jamali, E, Mehvar, R., and Pasutto, E M. (1989). Enantioselective Aspects of Drug Action and Disposition Therapeutic Pitfalls, /. Pharm. Set., 78 695-715. 

F. Jamali, R. Mehvar, and E M. Pasutto, "Enantioselective aspects of drug action and disposition Therapeutic pitfalls,". Pharm. Sci., 78 695-715 (1989). 

Enantioselectivity in Drug Action and Drug Metabolism The Beginnings... 

Kroemer, H. K., Gross, A. S., Eichelbaum, M. Enantioselectivity in drug action and drug metabolism influence on dynamics. In Pharmacodynamics and Drug Development (Cutler, N. R., Sramek, J. J., Narang, P. K., Eds). John Wiley Sons Chichester, 1994, pp. 103-114. 

For drugs to exert biological actions, contact with reaction partners in the body is required. When the reaction favors one of the enantiomers, enantioselectivity is observed. 

Scheme 32 outlines a high yielding approach to the enantiopure appetite suppressant drug 77. The reduction of the unsaturated aldehyde 74 was reported to occur with modest enantioselectivity in normal fermenting conditions with baker s yeast [155]. When the biotransformation is performed at very low substrate concentration, the e.e. can be raised to more than 90%, suggesting that incomplete enantioselectivity is due to the action of enzymes operating on the same substrate with opposite stereochemical preference [115]. However, an efficient transformation can be performed if the substrate concentration is controlled with the addition of absorbing hydrophobic resins. At 5 g/L 97% recovery and 98% e.e. was obtained. The halohydrin 75 obtained was transformed into the epoxide 76 and finally into the enantiopure 2-/ -benzylmorpholine 77, the more active enantiomer with appetite suppressant activity [26]. 

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