Z-D-Ala-Gly-NH2 → (S)-Benzyl (1-((2-amino-2-oxoethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate
Reaction equation
[NH:1]([C:11]([O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:12])[C@@H:2]([C:4]([NH:6][CH2:7][C:8]([NH2:10])=[O:9])=[O:5])[CH3:3].N(C(OC[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=O)[C@@H](C(NCC(N)=O)=O)CCC(=O)O.N(C(OCC1C=CC=CC=1)=O)[C@@H](C(NCC(N)=O)=O)CCCCN.N(C(C)=O)[C@@H](C(NCC(N)=O)=O)CC1C=CC=CC=1>>[NH:1]([C:11]([O:13][CH2:14][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1)=[O:12])[C@@H:2]([C:4]([NH:6][CH2:7][C:8]([NH2:10])=[O:9])=[O:5])[CH2:3][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1Participants
Procedure
For accurate comparison, the D-isomers Z-D-Phe-OBn, Z-D-Ala-OBn, Z-D-Glu-OMe, Z-D-Lys-OBn, and Ac-D-Phe-OBn (15-19) of the representative L-amino acids Z-L-Phe-OBn, Z-L-Ala-OBn, Z-L-Glu-OMe, and Z-L-Lys-SBn (1-4) examined in the previous ligation examples were used. The stereoselectivity of SBL-WT for L-amino acids was clear (Table 4), because none of the D-amino acid esters evaluated gave dipeptide products with WT as the catalyst. All of the S166C-MEs yielded dipeptide products containing D-amino acids Z-D-Phe-Gly-NH2, Z-D-Ala-Gly-NH2, Z-D-Glu-Gly-NH2, Z-D-Lys-Gly-NH2, and Ac-D-Phe-Gly-NH2 (20-24). While each of these enzymes still showed a preference for L-amino acids, yields of up to 66% of Z-D-Phe-Gly-NH2, using S166C—SCH2C6H5, over 0% for WT, demonstrated a dramatic improvement in SBL's acceptance of D-amino acids.
Sources & evidence
- ORD record
- ord-489839d11a1745f782da01bd26c7a789
- Source dataset
- uspto-grants-2003_06
- Patent number
- US06576454B2
Reaction notes
Loading…