5-tert-Butyl N-((phenylmethoxy)carbonyl)-L-glutamate → Z-Glu(OtBu)-Asn-OtBu

HRID 462863Notes

Reaction equation

HRID 462863 reaction equation
[NH:1]([C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[C@H:2]([C:12]([OH:14])=O)[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:10])([CH3:9])[CH3:8].[NH2:25][C@H:26]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][C:28](=[O:30])[NH2:29]>>[NH:1]([C:15]([O:17][CH2:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)=[O:16])[C@H:2]([C:12]([NH:25][C@H:26]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][C:28](=[O:30])[NH2:29])=[O:14])[CH2:3][CH2:4][C:5](=[O:11])[O:6][C:7]([CH3:8])([CH3:9])[CH3:10]

Participants

3

Reactant 2

HCID 1074725-tert-Butyl N-((phenylmethoxy)carbonyl)-L-glutamateHCID 6995006L-Asparagine tert-butyl ester

Product 1

HCID 13501932Z-Glu(OtBu)-Asn-OtBu

Procedure

Fragment I was prepared by stepwise chain elongation using the mixed anhydride procedure at -15° C. with careful temperature control. As seen in the scheme of FIG. 2 mixed anhydride (M.A.) coupling (isobutylchloroformate) of Z-Glu(OtBu)-OH with H-Asn-OtBu provided Z-Glu(OtBu)-Asn-OtBu. Catalytic hydrogenation (10% Pd-C) of this compound cleaved the N-terminal protective group and the dipeptide was coupled to Z-Ala-OH using mixed anhydride coupling to give Z-Ala-Glu (OtBu)-Asn-OtBu. The N-terminal was again deprotected by catalytic hydrogenation and the tripeptide coupled with Z-Glu(OtBu)-OH to give the protected tetrapeptide Z-Glu(OtBu)-Ala-Glu(OtBu)-Asn-OtBu which is deblocked by catalytic hydrogenation to provide the desired protected tetrapeptide (1).

Workup

  1. customFragment I was prepared by stepwise chain elongation
  2. customat -15° C.

Sources & evidence

ORD record
ord-722f8b12187d4458918d4776aef8c308
Source dataset
uspto-grants-1985_05
Patent number
US04517119

Reaction notes

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