Z-Phe-OBzl → (S)-Benzyl (1-((2-amino-2-oxoethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate

HRID 1937301Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1937301
[NH:1]([C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21])[C@@H:2]([C:10]([O:12]CC1C=CC=CC=1)=O)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[NH:30](C(OCC1C=CC=CC=1)=O)[C@@H:31]([C:33]([O:35]CC1C=CC=CC=1)=O)C.[NH:53](C(OCC1C=CC=CC=1)=O)[C@@H](C(OCC1C=CC=CC=1)=O)CCC(=O)O.N(C(OCC1C=CC=CC=1)=O)[C@H](C(OCC1C=CC=CC=1)=O)CC1C=CC=CC=1>>[NH:1]([C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])[C@@H:2]([C:10]([NH:30][CH2:31][C:33]([NH2:53])=[O:35])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Komponenten

5

Edukt 4

HCID 7016068Z-Phe-OBzl2×HCID 7018162Z-D-Glu-OBzlHCID 10781466Z-D-Ala-OBnHCID 10927237Z-D-Phe-OBn2×

Produkt 1

HCID 10937159(S)-Benzyl (1-((2-amino-2-oxoethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate

Versuchsvorschrift

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).

Quellen und Nachweise

ORD-Eintrag
ord-efd15600ffe443b7bce851bf6c612650
Quelldatensatz
uspto-grants-2002_05
Patentnummer
US06395532B1

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