Acid-base catalysis ternary mechanism

The findings of Swain and Brown 55) support the ternary mechanism proposed by Lowry for the mutarotation of tetra-O-methylglucose. It was found that the mutarotation of tetra-O-methylglucose in benzene in the presence of both an acid (phenol) and a base (pyridine) followed third-order kinetics but was first-order with respect to each component tetra-O-methyl-glucose, pyridine, and phenol 55). 2-Hydroxypyridine was found to be a very effective bifunctional catalyst, and since both acid and base functions were in the same molecule, the mutarotation followed second-order kinetics. Its catalytic action was essentially independent of the other acid and base species present. Although it is a much weaker acid or base than either phenol or pyridine, its catalysis of the mutarotation of tetra-O-methylglucose in benzene was much greater than that of either pyridine or phenol, or a mixture of both 55). 

Methyl transfer reactions play a significant part in the modifications of aromatic polyketides, both of the polyketide core [61,62] as well as of several of the sugar moieties [44,53]. In Streptomyces, more than 20 amino acid sequences have been found that may represent enzymes involved in methyl transfer reactions in the biosynthesis of aromatic polyketides [149]. One of these enzymes, the S-adenosyl-L-methionine-dependent DnrK, is involved in the methylation of the C-4 hydroxyl group in daunorubicin/doxorubicin biosynthesis (Scheme 10, step 12). The subunit of the homo-dimeric enzyme displays a fold typical for small-molecule methyltransferases. The structure of the ternary complex with bound products S-adenosyl-L-homocysteine and 4-methoxy-8-rhodomycin provided insights into the structural basis of substrate recognition and catalysis [149]. The position and orientation of the substrates suggest an Sn2 mechanism for methyl transfer, and mutagenesis experiments show that there is no catalytic base in the vicinity of the substrate. Rate enhancement is thus most likely due to orientational and proximity effects [149]. 

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