Peptides containing dipropylglycine

Abstract

Using 4‐heptanone in the Ugi reaction, it is possible to prepare a peptide containing a single residue of dipropylglycine (Dpg) in modest yield, but attempts to form peptides containing contiguous Dpg residues were unsuccessful. Methods of extending Dpg‐Dpg to higher homo‐oligomers have been examined. Carboxyl extension of N‐trifluoroacetyl (Tfa)‐Dpg2 is possible through its oxazolin‐5(4H)‐one, but only as far as the tripeptide. However, amino extension of Dpg2‐OButby successive steps of addition of 2‐trifluoromethyl‐4,4‐dipropyloxazolin‐5 (4H)‐one and N‐deprotection allowed preparation of Tfa‐Dpg6‐OButin good yield. Removal of the Tfa group from Dpg residues is only possible using sodium borohydride reduction under conditions which lead to partial reduction of the t‐butyl esters of protein amino acids. The use of the N'N'‐dibenzylhydrazide (DBH) group for C‐protection, however, circumvents this problem. Direct regeneration of carboxyl from DBH is possible with bromine in acetonitrile, and catalytic reduction gives the free hydrazide. Tfa‐Dpg‐NHNH2 can be oxidatively coupled to Gly‐OButbut not to Dpg‐OBut. Tfa‐Dpg3‐N3 undergoes Curtius rearrangement in preference to peptide bond formation, and Dpg3‐N3 eliminates isocyanic acid on heating to form N‐(Dpg)2‐heptylideneimine.