title: Peptides containing dipropylglycine. Part 2. Preparation of tripeptides and higher homo-oligomers of 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-OBut by successive steps of addition of 2-trifluoromethyl-4,4-dipropyloxazolin-5 (4H)-one and N-deprotection allowed preparation of Tfa-Dpg6-OBut in 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-OBut but 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.
mesh_terms: D008722:Methods; D009842:Oligopeptides / Q000138:chemical synthesis*; D014633:Valine / Q000031:analogs & derivatives*
chemical_list: D009842:Oligopeptides; C038263:dipropylglycine; D014633:Valine