Application of newly available bio-reducing agents to the synthesis of chiral hydroxy-β-lactams: model for aldose reductase selectivity

Homochiral 3-hydroxy-4-substituted β-lactams serve as precursors to the corresponding α-hydroxy-β-amino acids—key components of many biologically and therapeutically important compounds. We have developed a short synthetic sequence for these targets using a biocatalytic reduction to install the desired chirality. By employing 3-oxo-4-phenyl-β-lactam as a probe, 19 individual yeast reductases were screened for their efficiency and enantioselectivity with respect to this substrate. Four highly selective candidates all belonging to the aldose reductase (AKR) superfamily were identified. Two are Re-face selective and two are Si-face selective. The modelled three-dimensional structures of these enzymes provide a rationale for this behaviour and suggest strategies for their further improvement.

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