Chiral binding pocket

The molecular mechanism of the enantioselective protonation reaction by antibody 14D9 was revealed by a crystal structure analysis [19[. A catalytic carboxyl group AspH 101 was found at the bottom of the catalytic pocket and found to be necessary for catalysis by mutagenesis to Asn or Ala. The mechanism or protonation involves an overall syn addition of water to the enol ether in a chiral binding pocket ensuring complete enantioselectivity (Figure 3.4). 

The lack of resolution by which mechanism the osmylation proceeds has resulted in two models to rationalize the face selectivity of the AD reaction. The commonality of these two predictive models resides in the basic principle that a chiral binding pocket is formed from the ligand s aromatic groups. However, the shape and location of this pocket in the complex is not identical. 

Gagne et al. [21] have also utilized this strategy of selectively blocking or poisoning sites in an MIP in order to try to improve catalytic activity and selectivity. An MIP was synthesized containing catalytically active Pt(II) centers within a chiral binding pocket. The MIP was shown to be able to catalyze the ene reaction of methylenecyclohexane with ethylglyoxylate (Scheme 6). It was hoped that the chiral pocket of the MIP would catalyze the ene reaction in an enantioselective fashion. 

Roles of the osmaoxetane complexes lA and IB as intermediates has been proposed, and the fundamental mechanism for face-selectivity involves the reaction between the olefin and OSO4 within the chiral binding pocket created by the chiral ligand L [29, 30]. 

To examine the possibility of a more selective catalytic olefin metathesis, we first prepared chiral Mo-based complexes, 4a and 4b [10]. This approach was not without precedence related chiral Mo complexes were initially synthesized in 1993 and used to promote polymer synthesis [6], We judged that these biphen-based systems would initiate olefin metathesis with high asymmetric induction due to their rigidity and the steric differentiation imposed on the chiral complex s binding pocket. Mo complexes 4a and 4b are orange solids and indefinitely stable when kept under an inert atmosphere. 

A ligand with a more direct interaction between chiral centers and the substrate binding pocket is the bis(phospholane) (22-XII) 11 rhodium hydrogenation catalysts... 

Finally, the bacterial PTE mentioned above has also been exhaustively studied with regard to its enantioselectivity. Initial studies used the known crystal structure of PTE to identify the substrate-binding pocket. This was then rationally evolved for enhancement and relaxation of the stereospecificity.97 Most recently, a combinatorial library has been screened for the resolution of chiral phosphate, phosphonate, and phosphinate esters.124 This work identified two variants with markedly different preferences for 5p- and Rp-enantiomers of 4-acetylphenyl methyl phenyl phosphate. One variant preferentially catalyzed hydrolysis of the 5p-enantiomer by a factor of 3.7 x 105, while the other preferentially catalyzed hydrolysis of the A p-enantiomer by a factor of 9.7 x 102 - an enantioselective discrimination of 3.6 x 108. 

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