Glycinamide hydrochloride → Z-D-Ala-Gly-NH2

HRID 1937302Notes

Reaction equation

HRID 1937302 reaction equation
[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:15])[C@@H:2]([C:4]([O:6]CC1C=CC=CC=1)=O)[CH3:3].[NH:24]([C:41]([O:43][CH2:44][C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)=[O:42])[C@@H:25]([C:31]([O:33]CC1C=CC=CC=1)=O)[CH2:26][CH2:27][C:28](=[O:30])[OH:29].Cl.[NH2:52][CH2:53][C:54]([NH2:56])=[O:55]>>[NH:1]([C:14]([O:16][CH2:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:15])[C@@H:2]([C:4]([NH:52][CH2:53][C:54]([NH2:56])=[O:55])=[O:6])[CH3:3].[NH:24]([C:41]([O:43][CH2:44][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)=[O:42])[C@@H:25]([C:31]([NH:52][CH2:53][C:54]([NH2:56])=[O:55])=[O:33])[CH2:26][CH2:27][C:28](=[O:30])[OH:29]

Participants

5

Reactant 3

HCID 2723639Glycinamide hydrochlorideHCID 7018162Z-D-Glu-OBzl2×HCID 10781466Z-D-Ala-OBn2×

Product 2

HCID 11437420Z-D-Ala-Gly-NH2Yield 86%HCID 100979520Z-D-Glu-Gly-NH2Yield 74%

Procedure

Next, the extension of the use of the MEs to the coupling reaction of D-amino acids as acyl donor, Z-D-Phe-OBn (28), Z-D-Ala-OBn (29), and Z-D-Glu-OBn (30) with Z-L-Phe-OBn (1) was examined. While WT enzyme did not accept D-amino acids as acyl donors, all of the MEs were able to catalyze the coupling of D-amino acids with Z-L-Phe-OBn (1). Although the reactions of Z-D-Phe-OBn (28) in all cases were slow to give Z-D-Phe-Gly-NH2 (39) in low yield (the best was 14% by using M-n), peptide coupling of Z-D-Ala-OBn (29) or Z-D-Glu-OBn (30) with Gly-NH2 (31) proceeded without remaining substrates. It is noteworthy that using ME-k and -m in case of Z-D-Ala-OBn (29) and ME-o in case of Z-D-Glu-OBn (30) gave Z-D-Ala-Gly-NH2 (37, 86%) and Z-D-Glu-Gly-NH2 (38, 74%), respectively, in very high yields. Probably, the CMMs recognized D-amino acids in a different manner from L-amino acids, i.e., the carbobenzoxy group of α-position seems to bind the S1 pocket. On the other hand, repulsion between the phenylmethyl group of Z-D-Phe-OBn (28), which had the biggest substituent among the three kinds of substrate, and the other parts in the pocket of active site of the MEs could cause low reactivity of Z-D-Phe-OBn (28).

Workup

  1. customin low yield (the

Sources & evidence

ORD record
ord-f7d80c196b3e43b399273b09abc5e111
Source dataset
uspto-grants-2002_05
Patent number
US06395532B1

Reaction notes

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