Stereoselective transport

Hooiveld, G. J., Heegsma, J., van Monteoort, J. E., Jansen, P. L., Meijer, D. K., Muller, M., Stereoselective transport of hydrophilic quaternary drugs by human MDR1 and rat Mdrlb P-glycoproteins,... 

T. Yoshikawa, N. Muranushi, M. Yoshida, T. Oguma, K. Hirano, and H. Yamada, Transport characteristics of ceftibuten (7432-S), a new oral cepham, in rat intestinal brush-border membrane vesicles Proton-coupled and stereoselective transport of ceftibuten, Pham. Res., 6 302-307 (1989). 

In light of these developments, we felt that it was necessary to review the content of the first edition and to update or supplement the information presented in this work. The new topics examined in this edition include (1) enzymatic synthesis and resolution of enantiomerically pure compounds (Chapter 8) (2) toxicological consequences and implications of stereoselective biotransformations (Chapter 9) (3) stereoselective transport across epithelia (Chapter 10) and (4) assessment of bioavailability and bioequivalence of stereoisomeric drugs (Chapter 11). The chapter on stereoselective protein binding (Chapter 12) has been completely revmtten and new contributions are presented on the regulatory, industrial, and clinical aspects of stereoisomeric drugs (Chapters 13-16). In addition, the chapters... 

The use of chiral membrane solvent to achieve transport stereoselectivity is not very widespread. Probably, the only report describing chiral hquid-phase-enhanced stereoselective transport is amino acid enantiomers separation by means of chiral alcohols, nopol and (2S)-(—)-methylbutan-l-ol [38] (see Fig. 3.9). It was shown that optical separation of six pairs of enantiomers of amino acids is possible in this way. However, the chiral discrimination (expressed as a flux ratio for both enantiomers and denoted as a) was moderate and the best result was 1for serine. As a main conclusion, it was stated that the factor involved in chiral discrimination was an asymmetry of the amino acid molecule. 

Dzygiel, P., Wieczorek, P. (2002). Stereoselective transport of amino acids and peptides through hquid membranes. Chem. Pap., 56, 24-31. 

Langen, K.-J. Hamacher, K. Bauer, D. Brder, S. Pauleit, D. Herzog, H. Floeth, R Zilles, K. Coenen, H.H. Preferred stereoselective transport of then-isomer of cA-4-[ F] fluoro-proline at the blood-brain barrier. J. Cereb. Blood Flow Metab. 2005,25, 607-616. 

All orally active (3-lactams carry an unsubstituted or modified D-phenylglycine side group in the A-terminus position and therefore should have affinities similar to di- and tripeptides with an A-terminal D-amino acid [14]. The stereoselective transport of (3-lactam antibiotics is of particular interest because the L-isomer of aminocephalosporin failed to be absorbed in vivo to a significant extent [15]. However, a study on d- and L-enantiomers of cephalexin and loracarbef demonstrated the higher affinity of the L-isomer to oligopeptide transporter than the o-isomer (Fig. 5) [16]. Consequently, the apparent low absorption rate of L-isomers of amino cephalosporines does not appear to be due to lack of transport by the peptide transporter, but, more likely, because of the rapid enzymatic... 

Ahmed, S. Imai, T. Otagiri, M. Evaluation of stereoselective transport and concurrent cutaneous hydrolysis of several ester prodrugs of propranolol mechanism of stereoselective permeation. Pharm. Res. 1996, 13, 1524-1529. 

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