Using thiamin diphosphate condensations

More recently, enzymatic carboligation in a solid/gas bioreactor was demonstrated to be possible [55] in a model system based on the condensation of two propanal molecules to produce of propioin using thiamine diphosphate-dependent... 

The erythrose 4-phosphate generated in the same step (Scheme 11.7) as the derivative of thiamine diphosphate is then available for enzyme-catalyzed aldol-type condensation with dihydroxyacetone monophosphate just as shown in Scheme 11.5 for the analogous reaction with glyceraldehyde 3-phosphate and using the same fructose-bisphosphate aldolase (EC 4.1.2.13). 

The cross-benzoin reaction between two different aldehydes typically produces a statistical mixture of products, although in some cases a single thermodynamic product predominates. A number of approaches have been developed to circumvent the limitations of the cross-benzoin reaction. In one approach, a thiamine diphosphate-dependent enzyme is used to promote a selective cross-benzoin reaction, often with high levels of asymmetric induction. In other approaches, one aldehyde coupling partner is replaced with a selective acyl donor. Cyanohydrin derivatives have proven to be ideal preformed acyl donors, and their use constitutes a stepwise benzoin condensation that is stoichiometric in cyanide. The discovery that acylsilanes can serve as cyanohydrin precursors has led to the development of a highly selective cyanide-catalyzed cross-benzoin condensation. By employing a chiral metallophosphite catalyst instead of potassium cyanide, good to excellent levels of asymmetric induction are possible. 

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. ... 

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