Peptides with C-terminal aldehydes (PAs) are of interest due to their
inhibitory properties toward numerous classes of proteolytic enzymes.
In this paper, we describe and compare two novel approaches for the pr
eparation of PAs by solid phase synthesis, one based on the reduction
of the Weinreb amide and the other on the reduction of phenyl esters.
A study showed that purification of the PAs by chromatography (silica
gel or reversed phase) induced a loss of the optical integrity of the
C-terminal residue. Both methods were found to be suitable for the syn
thesis of PAs which were then used for the preparation of reduced-bond
-containing peptides on insoluble polymers. The Weinreb amide approach
was preferred for the synthesis of PAs due to an uncontrolled over-re
duction of phenyl esters in our hands.