Thiamin-diphosphate-dependent enzymes: new aspects of asymmetric C-C bond formation.
Starting from a thorough investigation of mechanistic aspects of ThDP-dependent (ThDP = thiamin diphosphate) enzymes in combination with mutagenesis studies and a detailed substrate screening, new general synthetic methods have been developed based on Umpolung reactions by thiamin catalysis. A selective donor-acceptor concept was established leading to the first asymmetric cross-benzoin condensation, and a kinetic racemic resolution through C-C bond cleavage was developed. With these tools and in combination with protein engineering, we approached the synthesis of new chiral building blocks on a preparative scale. An outlook is given with respect to the potential of other ThDP-dependent enzymes as catalysts in asymmetric synthesis.
Pohl
Martina
M
Institut für Enzymtechnologie Heinrich-Heine-Universität Düsseldorf 52426 Düsseldorf, Germany.
Lingen
Bettina
B
Müller
Michael
M
D000446:Aldehyde-Lyases / Q000737:chemistry / Q000378:metabolism*; D001419:Bacteria / Q000201:enzymology / Q000235:genetics; D002262:Carboxy-Lyases / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D011767:Pyruvate Decarboxylase / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013831:Thiamine / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000737:chemistry / Q000378:metabolism*
D002262:Carboxy-Lyases; D011767:Pyruvate Decarboxylase; C019778:benzoylformate decarboxylase; D000446:Aldehyde-Lyases; C059416:benzaldehyde lyase; D013835:Thiamine Pyrophosphate; D013831:Thiamine