Reaction intermediate analogs, design

The 2-azonia analog of the Cope rearrangement is estimated to be accelerated by 106, relative to the unsubstituted system.270 The product of the rearrangement is an isomeric iminium ion, which is a mild electrophile. In synthetic applications, the reaction is often designed to generate this electrophilic site in a position that can lead to a cyclization by reaction with a nucleophilic site. For example, the presence of a 4-hydroxy substituent generates an enol that can react with the iminiun ion intermediate to form a five-membered ring.271... 

H) Search for inhibitors Several phosphonic derivatives, designed as analogs of the reaction intermediates, have been tested." " Three of them, 7, 8, and 9 (Figure 10) were found to be competitive inhibitors of L-Ala with good affinities, revealed by the low values of Ki/Kyi Ala. The best one is compound 7, an analog of [I], which cannot decarboxylate, with a A) of 7 pmoll (3.5 pmoll if we assume that only one... 

Recently, it has been shown that there are NAD-dependent oxidoreductases that will not liberate NADH/NAD+ from the active site. They catalyse such redox reactions, albeit not with formate but with less favourable electon donors and with low rates [9]. When these enzymes can be properly engineered and produced, they will impose few constraints on the reactor design. This situation is analogous to what has been described in the previous section for synthetic reactions using hydrolases if a biocatalyst is found that can directly convert the substrates into the desired products, without formation of intermediates or occurrence of side-reactions, the reactor design becomes simple. 

Rh(II) carboxylates, especially Rh2(OAc)4> have emerged as the most generally effective catalysts for metal carbene transformations [7-10] and thus interest continues in the design and development of dirhodium(II) complexes that possess chiral51igands. They are structurally well-defined, with D2h symmetry [51] and axial coordination sites at which carbene formation occurs in reactions with diazo compounds. With chiral dirhodium(II) carboxylates the asymmetric center is located relatively far from the carbene center in the metal carbene intermediate. The first of these to be reported with applications to cyclopropanation reactions was developed by Brunner [52], who prepared 13 chiral dirhodium(II) tetrakis(car-boxylate) derivatives (16) from enantiomerically pure carboxylic acids RlR2R3CC OOH with substituents that were varied from H, Me, and Ph to OH, NHAc, and CF3. However, reactions performed between ethyl diazoacetate and styrene yielded cyclopropane products whose enantiopurities were less than 12% ee, a situation analogous to that encountered by Nozaki [2] in the first applications of chiral Schiff base-Cu(II) catalysts. 

The free energies of activation associated with different transition states differ only by about 1.5 kcal. Methyl migration is partially rate determining, but there is no analogous H migration as found with 1 and 2. Formation of intermediates like 182 by reaction of the reactive zwitterion with the solvent has been designated as solvent trapping. 

The characteristics of intermediates MMOH-Q and RNR R2-X continue to converge. The radiolytic reduction of MMOH-Q affords an Fe(III)/Fe(I V) form designated Qx, which has Mossbauer properties similar to RNR R2-X [25]. This work and the recent EXAFS characterization of MMOH-Q and RNR R2-X [26-28], revealing that the two intermediates have very similar core structures, provide strong support that the 02 reaction chemistry in these two enzymes is analogous. This notion very likely extends to the other diiron oxygen activating enzymes. 

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