anti-malarial 3 synthesis proposal
Here is an example of a synthesis using the solid-support strategy described previously using standard Merrifield polypeptide synthesis conditions. All compounds are commercially available from Sigma-Aldrich but the tBOC amino acid derivatives were not in Chmoogle. Also the only listed source of the commonly available bromoacetone was a private collection. So it seems Chmoogle should be used cautiously to determine commercial availability.
Steps A and B should proceed without difficulty. Step C is more problematic. Polyalkylation of the primary amine or alkylation of the phenols may occur also. An alternative to step C might be reductive amination with pyruvaldehyde. I think the aldehyde end will preferentially form the imine over the ketone. I am also concerned with the cyclization to the diketopiperazine - will that be problematic for a secondary amine? The reaction conditions for cyclization are given previously.
If anyone has a suggestion or comment about my proposed synthesis please contribute.
ChemSketch File of this Synthesis