Convergent synthesis of potent peptide inhibitors of the Grb2-SH2 domain by palladium catalyzed coupling of a terminal alkyne

J Schoepfer, B Gay, N End, E Muller, G Scheffel…

Index: Schoepfer, Joseph; Gay, Brigitte; End, Nicole; Muller, Evelyne; Scheffel, Gisela; Caravatti, Giorgio; Furet, Pascal Bioorganic and Medicinal Chemistry Letters, 2001 , vol. 11, # 9 p. 1201 - 1203

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Citation Number: 14

Abstract

A new strategy was developed to prepare in a very efficient and convergent manner C- terminal modified tripeptides with high affinities for the Grb2-SH2 domain. Using Pd (PPh3) 2Cl2 as catalyst, selected naphthyl iodides and triflates were coupled to Ac-Pmp (t-Bu) 2- Ac6c-Asn-NH (prop-2-ynyl). The resulting alkyne derivatives were hydrogenated and deprotected to afford potent Grb2-SH2 inhibitors.