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

HRID 583004Notes

Reaction equation

HRID 583004 reaction equation
[O:1]=[C:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1.CC1(C)O[C@]2(OC[C@@H]3OC(C)(C)O[C@@H]3C2=O)CO1>>[OH:1][C@@H:2]1[CH2:6][NH:5][C@H:4]([C:7]([OH:9])=[O:8])[CH2:3]1

Participants

3

Reactant 2

HCID 1075414-oxo-L-proline2×HCID 11391247L-enantiomer

Product 1

HCID 440015Cis-4-Hydroxy-L-Proline

Procedure

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.

Workup

  1. customwill typically produce
  2. additiona racemic mixture of two enantiomers

Sources & evidence

ORD record
ord-3fc64090c0c144b29fa1fab641e7d69f
Source dataset
uspto-grants-1999_07
Patent number
US05928933

Reaction notes

Loading…