Stereochemical control in the preparation of α-amino N-methylthiazolidine masked aldehydes used for peptide aldehydes synthesis

Chiral N-methyl thiazolidines masked α-amino aldehydes are used for solid phase peptide aldehyde elongation. Contrary to N-Boc-protected α-amino aldehydes, N-trityl protection secures the chiral integrity of the incoming aldehyde chiral C1′ carbon atom during condensation of the amino aldehydes with l-cysteinyl residues. The Ac-Tyr-Val-Ala-Asp-H caspase inhibitor was prepared on a solid support starting from the N-trityl-amino thiazolidine masked aspartinal as a validation of this process.