4-oxo-L-proline → Cis-4-Hydroxy-L-Proline

Participants

Reaction Steps

Chemical synthesis of 4-ketoproline derivatives from inexpensive achiral starting materials will typically produce a racemic mixture of two enantiomers. It has been reported that hydrogenation of either D- or L-enantiomer of 4-ketoproline derivatives can produce the corresponding cis-4-hydroxyproline derivatives with high selectivity (Kuhn et al., Chem. Ber. 89:1423 (1956)), so an enzymatic resolution of a racemic mixture of D- and L-4-ketoproline derivatives would allow for the hydrogenation of the 4-keto-D-proline derivative to produce CHDP. Chemical or enzymatic racemization of the remaining 4-keto-L-proline derivative to a 50/50 mixture of D- and L-isomers could allow the undesired L-isomer to be recycled back into the resolution step. Alternatively, if the 4-keto-L-proline derivative could be reduced and hydrolyzed to THLP, the THLP is readily converted to CHDP by chemical isomerization.

Provenance & Evidence