Site epimerisation

Casey was able to prepare related zirconocene alkenyl complexes according to Scheme 8.18. Alkene coordination was established by a number of NMR techniques. While zwitterionic compounds 38 allowed the determination of the alkene dissociation energy, AG = 10.5 kcal mol , very similar to that of 35. Thermally more stable complexes were obtained by protonation of 37 with [HNMePh2][B(C5F5)4[. Dynamic NMR spectroscopy and line shape analysis allowed the measurement of the barriers of alkene dissociation (AG = 10.7 and 11.1 kcal mol ), as well as for the site epimerisation ( chain skipping ) at the zirconium center (AG = 14.4 kcal mol" ) (Scheme 8.19) [77]. 

Neutral lanthanide complexes are convenient models for the cationic zirconocene systems and avoid complications due to the presence of counteranions and the limited solubility of ionic compounds. Dynamic NMR studies on yttrium complexes 44-46 has allowed the determination of the alkene binding enthalpy, the activation enthalpy of alkene dissociation, and the relative rates of dissociation and alkyl site exchange (site epimerisation) (Scheme 8.20). Compared to the Zr... 

The GDP-6-deoxy-4-keto-D-mannose then can either be reduced, giving GDP-D-rhamnose (the unusual stereoisomer of rhamnose), or be isomerised at positions 3 and 5 and reduced to L-fucose at the active site of an unusual bifunctional enzyme, which is both reductase and isomerase. The reduction occurs with proS (B-side) specificity of the NADPH coenzyme and the enzyme will catalyse epimerisation and exchange of H3 and H5 in the absence of NADPH.The available structures of the E. coli enzyme" " show NADPH bound in the expected syn conformation and counterparts to the His and Lys suggested to play a role in the action of the dTDP-6-deoxy-4-ketoglucose isomerase in the correct position. 

Around neutral pH a-penici)loyl esters [68] epimerise at C(5) faster than the ester function is hydrolysed (Davis and Page, 1985). If this occurs with penicilloyl enzymes from penicillins and the serine hydroxyl at the active site of the enzyme, the ring-opening of the thiazolidine generates electrophilic sites capable of irreversibly inactivating the enzyme. 

Many of the mechanistic aspects of glucose isomerase catalysed aldose-ketose interconversion have been under discussion for some time and are still not fully understood. By comparison with triose phosphate isomerase (TIM, EC 5.3.1.1) and glucose 6-phosphate isomerase (EC 5.3.1.9), the base-catalysed formation of an 1,2-enediol was invoked as the key step of the epimerisation based on the work of Rose and co-workers with tritium-labelled substrates [26]. An unexplained featme of the epimerisation process was that in contrast to isomerisations with triose phosphate isomerase no proton exchange with the medium could be observed with D-xylose isomerase, a fact that was attributed to the phosphate group of the former as a mediator for the exchange process [26]. Subsequently, additional important differences between triose phosphate isomerase and xylose isomerase were recognised. For example, D-xylose isomerase is appar-endy a very slow enzyme catalysing about five molecules per second per active site with an absolute requirement for divalent cations, while TIM does not need co-factors and operates at nearly 1000-fold the speed of D-xylose isomerase at... 

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