Peptide aldehydes by solid phase synthesis

We have focused our attention on the solid phase synthesis of such compounds and described our results here. Alternative routes for the preparation of peptide aldehydes and side-chain protected peptide aldehydes in solid phase synthesis are described. Three new linkers that are stable tmder classical Fmoc or Boc strategies have been developed to obtain the peptide aldehyde from the solid support. One of these linkers was conceptualized on the basis of the Weinreb amide (49) and the other on the basis of phenolic esters (50). Both strategies required the reduction with hydrides of the peptide-linker-resin to release the peptidic aldehydic function. The use of these two different approaches was demonstrated by the synthesis of N-protected a-amino-aldehydes and peptide aldehydes, llie third approach used the ozonolysis reaction for the generation of the desired aldehyde. This concept requires a linker incorporating a double bond in the a-position of the asymmetric carbon of the C-terminal residue that will be cleaved by ozone to produce the carbonyl function. 

Among all the described preparations of N-protected amino aldehydes and peptide aldehydes, the redaction of Weinreb amides is used most widely. This 

This methodology was validated by the synthesis of Boc-Ala-H and Boc-Phe-H these compounds were purified on a silica gel column according to the procedure described by Ho and Ngu (52) to prevent racemization during purification. Their optical purities were in accordance with those reported in the literature (53). 

In all reactions, no over-reduction was observed, confirming the formation of the stable metal-chelate intermediate described by Nahm and Weinreb (49). Furthermore, during the reduction, no aldehyde derivative could be 

Protocol 9. Preparation of peptide aldehydes by reduction of a polymer-supported Weinreb amide 

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