Bioorganic modelling stereoselective reactions with chiral neutral ligand complexes as model systems for enzyme catalysis.
In terms of the reporting of accomplished chemistry this review can do no more than give an indication of the rapid progress in the branch of bioorganic modelling based on the use of macrocyclic compounds that (usually) act as complexing agents. What remains to be done, however, is to point out problems that have not been satisfactorily solved and to suggest other profitable areas of investigation. From the material accumulated in this review one can draw the conclusion that especially crown (or cryptate) systems offer special advantages in bioorganic modelling because such compounds can - enzyme like - complex a potential substrate. On the basis of quite simple binding considerations, coupled with an analysis of steric interactions, accurate predictions of the stereochemistry of the complex can be made. The inclusion of catalytic groups in the crown (or cryptate) system and reactive functional groups in the substrate is then done in such a fashion that the stereoelectronic arrangement is compatible with the predicted geometry of the complex. However, the good complexing ability of the ligand is paradoxically often its greatest failing in terms of developing a system in which the functionalized ligand acts truly as a catalyst. As seen from much of the chemistry discussed in this review the ligand is incapable of the double task of complexing substrate but releasing product in an enzymic fashion, i.e. that turnover occurs. How is this problem to be solved? Induced conformational changes are an obvious approach although the design of proper systems remains a challenge for which few suggestions outside of unlimited ingenuity can be given. Much of the solution to such problems will lie also in a much better understanding than we now have of non-covalent interactions and the stereochemistry of such interactions. The assembly and disassembly of large molecular aggregates by the making and dissolution of non-covalent bonds is an art at which chemists are still relative amateurs. A better understanding of non-covalent interactions may also provide the key to achieving also the twin goals of both speed and selectivity in bioorganic modelling. As far as enantioselectivity is concerned it is clear that this can be achieved fairly effectively by the use of relatively small, but appropriately placed, groups that force the substrate to complex in an enantioselective step with the ligand. In other words, the problem of enantioselectivity can be solved at the stage of complex forming, which is kinetically rapid. The p]roblem of rate enhancement lies in the mentarity with the transition state of the reaction being catalyzed. Again the achievement of this goal lies in ingenuity of design. Potential areas of applications of chiral crown ether (or cryptate) ligand systems in bioorganic modelling lie in, for example, the formation of carbon-carbon bonds, development of oxidative processes (i.e...
D055598:Chemical Phenomena; D002621:Chemistry; D004798:Enzymes / Q000378:metabolism*; D004987:Ethers; D006838:Hydrocarbons; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D010088:Oxidoreductases / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides; D011485:Protein Binding; D013329:Structure-Activity Relationship
D004798:Enzymes; D004987:Ethers; D006838:Hydrocarbons; D008024:Ligands; D010455:Peptides; D010088:Oxidoreductases; D010447:Peptide Hydrolases