Physical Sciences and Mathematics Commons^™

Synthetic Routes To Therapeutic Agents Via Masked Functionalities: From Orthogonal Peptide Crosslink To Photothermal Cancer Prodrug, Chyree Shantel Batton

LSU Doctoral Dissertations

The theonellamides are a family of compounds distinguished by their crosslinking ô-histidinoalanine (ô-HAL) residue. Part one of this dissertation details the synthesis of an orthogonally protected ô-HAL building block that will be incorporated into a total synthesis of theonellamide C. Selective deprotection of each amine and acid of this orthogonally protected building block is also demonstrated. Various reaction partners for the assembly of ô-histidinoalanine were explored. One approach involved the coupling of N-Fmoc-â-iodoalanine benzyl ester and (Nðim)-blocked histidine nucleophiles including a fused bicyclic urea and a Boc-His(Nð-Pac)-OMe. While the imidazolium salts were identified by mass spectrometry, elimination of the iodide …