Formation of Chiral 2-Hydroxy Ketones Through BFD-Catalyzed Reactions

1 Formation of Chiral 2-Hydroxy Ketones Through BFD-Catalyzed Reactions 

The potential of benzoylformate decarboxylase (BFD, E.C. 4.1.1.7) to catalyze C-C bond formation was first reported by Wilcocks at al. using crude extracts of Pseudomonas putidsL [50]. They observed the formation of (S)-2-hydroxy-l-phenylpro-panone (S)-2-HPP when benzoyl formate was decarboxylated in the presence of acetaldehyde. Advantageously, aldehydes - without a previous decarboxylation step - can be used instead of the corresponding more expensive a-keto acids [51]. We could show that BFD is able to bind a broad range of different aromatic, heteroaromatic, and even cyclic aliphatic and conjugated olefinic aldehydes to ThDP before ligation to acetaldehyde or other aldehydes (Table 2.2.7.3) [52]. 

The best results with respect to the enantiomeric excess (ee) of the resulting 2-hydroxy ketones were obtained with meta-substituted benzaldehydes. When these substrates were used, the ee increased to more than 99%, indicating that the steric demand and electronic properties of the substituent play a decisive role in both conversion rate and ee (Table 2.2.7.3, entries 2-4). Ortho-substituted benzalde- 

In contrast to the large variety of aromatic, olefinic, and aliphatic aldehydes which can be used as donor substrates, wild-type BFD does not tolerate a modification of the methyl group of acetaldehyde in the case of aliphatic acceptor aldehydes. Apart from acetaldehyde, BFD shows activity with aromatic and heteroaromatic aldehydes as the acceptor substrate, forming enantiomerically pure (R)-benzoin and derivatives (Table 2.2.7.3, entries 6-8) [55]. 

Biotransformation of hydrophobic aldehydes is possible in the presence of water-miscible organic solvents. The best results with regard to an increased solubility of hydrophobic substrates together with the least loss of ligase activity of BFD were obtained by addition of DMSO [56]. In doing so, enantiomerically pure (R)-benzoin was obtained in 70% isolated yield [55]. 

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