Solid-phase total synthesis of trunkamide A

Marine organisms are a rich source of novel, biologically active compounds. Herein, the solid-phase total synthesis of trunkamide A, currently in prec linical trials, is presented. Trunkamide A contains a thiazoline heterocycl e and two residues of Ser and Thr with the hydroxy function modified as rev erse prenyl (rPr). Cornerstones of the synthesis are as follows: (i) solid- phase peptide chain elongation using a quasi-orthogonal protecting scheme w ith tert-butyl and fluorenyl based groups, on a chlorotrityl resin; (ii) co ncourse of HOAt-based coupling reagents; and (iii) cyclizations in solution . Furthermore, the following synthetic steps are discussed: (i) preparation of the reverse prenyl derivatives of Ser and Thr; (ii) introduction of pre cursor of thiazoline as a protected amino thionoacid derivative; and (iii) formation of the thiazoline ring with DAST, All these features make this st rategy particularly suitable for the large-scale synthesis of trunkamide A and other peptides containing the same motifs.