Using thiamin diphosphate ThDP-dependent

CARBON-CARBON BOND FORMATION USING THIAMIN DIPHOSPHATE (THDP)-DEPENDENT CARBOLIGASES... 

Pyruvate oxidase (Pyox) is a FAD- and thiamine diphosphate (ThDP)-dependent enzyme that catalyzes the reaction of pyruvate to give acetyl phosphate or vice versa (see Fig. 15). If used in the oxidative way, it can be activated and reactivated under nonaerobic conditions using ferrocene mediators. Kinetic parameters of the indirect electrochemical process using the enzyme incorporated into a biomimetic supported bilayer at a gold electrode have been reported [142]. Similarly, FAD-dependent amino oxidases may also be applied. 

An associated cascade process that combines a thiamine diphosphate (ThDP)-dependent ligase with enantiocomplementary m-TAs was described recently to access norephedrine (NE) and norpseudoephedrine (NPE) in only two steps from cheap starting materials [52]. The system uses the acetohydroxyacid synthase I (AHAS-I) from E. coli to yield (P)-phenylacetylcarbinol [(R)-PAC, 98% ee] via carboligation with benzaldehyde, which was then directly converted to the desired ephedrine derivatives (NE or NPE) by the appropriate choice of m-TA (Scheme 4.15). Moreover, a novel cascade was introduced with this system ( recycling cascade ) because the coproduct of the reductive amination (pyruvate) could be elegantly removed/recycled without addition of further catalyst, increasing thereby the intrinsic overall efficiency. Several aminotransferases were tested initially for the reductive amination because the benzaldehyde also serves as a suitable substrate for... 

Milller and co-workers recently developed an enantioselective benzoin dimerization using purified enzymes from Pseudomonas. The thiamine diphosphate (ThDP) dependent enzymes benzaldehyde lyase (BAL) and benzoylformate decarboxylase (BED) were found to catalyze the reversible benzoin condensation of aromatic aldehydes. The reaction is driven in the forward direction by the poor solubility of the benzoin products in aqueous media. A wide variety of aromatic aldehydes are accepted by BAL, and products of the (/ )-configuration are produced in excellent yield and enantiomeric purity. The (S)-enantiomer of benzoin is also available in high enantiomeric purity from a BAL-catalyzed kinetic resolution of rac-benzoin. In the presence of excess acetaldehyde, BAL selectively converts (i )-benzoin into (/ )-2-hydroxy-l-phenylpropanone, while the (iS)-benzoin enantiomer is not a substrate for the enzyme. At 49% conversion, (5)-benzoin is resolved to > 99% ee. BED can produce (i )-benzoin from benzaldehyde in comparable yield and enantiomeric purity with respect to BAL, but the substrate scope appears more limited. ... 

For this type of C-C bond formation both stereoisomers of the hydroxyphenyl-propanone can be obtained using either the BFD mentioned above or the benz-aldehyde lyase (BAL). Both of these enzymes are dependent on thiamine diphosphate (ThDP) as cofactor [22]. For the enantioselective reduction of the intermediate also, both stereoisomers can be obtained by using two different ADH enzymes. Thus all four possible stereoisomers of the diol can be obtained in high optical purity (see Scheme. 3.1.1) [23]. 

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