Glycinamide → Z-Phe-ala-NH2

HRID 1937296Notes

Reaction equation

HRID 1937296 reaction equation
[NH2:1][C@H:2]([C:4]([NH2:6])=[O:5])[CH3:3].[NH:7]([C:26]([O:28][CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)=[O:27])[C@H:8]([C:16]([O:18]CC1C=CC=CC=1)=O)[CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.NCC(N)=O>>[NH:7]([C:26]([O:28][CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1)=[O:27])[C@H:8]([C:16]([NH:1][C@H:2]([C:4]([NH2:6])=[O:5])[CH3:3])=[O:18])[CH2:9][C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

4

Reactant 3

HCID 69020GlycinamideHCID 444939L-AlaninamideHCID 7016068Z-Phe-OBzl2×

Product 1

HCID 7020268Z-Phe-ala-NH2

Procedure

In all cases, the reaction of L-Ala-NH2 (6) with Z-L-Phe-OBn (1) was slower than Gly-NH2 (5) with Z-L-Phe-OBn (1). Further, after 24 hours, Z-L-Phe-Ala-NH2 (11) was obtained in moderate yield (33-57%) using WT, S166C—SCH2C6H5, —SCH2C6F5, and —SCH2(p-COOH—C6H4) as the catalysts. However, Z-L-Phe-Ala-NH2 (11) was obtained in 88% yield in the case of S166C—SCH2CH2NH3+. Unlike S166C—SCH2CH2NH3+, the use of M222C—SCH2CH2NH3+ did not improve the yield of the dipeptide product as compared to the WT-catalyzed reaction; only a low 22% yield of Z-L-Phe-Ala-NH2 (11) was obtained. This was possibly due to the steric interaction of this residue at the binding site, S1pocket, with the P1 substrate as mentioned above.

Sources & evidence

ORD record
ord-5f4aed4b3267481bb879c586f87dac4a
Source dataset
uspto-grants-2002_05
Patent number
US06395532B1

Reaction notes

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