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

Participants

Reaction Steps

Fragment I was prepared by stepwise chain elongation using the mixed anhydride procedure at -15° C. with careful temperature control. As seen in Scheme 1 of FIG. 2 mixed anhydride 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 tetrapeptide (I).

Provenance & Evidence