| Abstract
| - Marine organisms are a rich source of novel, biologically active compounds. Herein, the solid-phasetotal synthesis of trunkamide A, currently in preclinical trials, is presented. Trunkamide A containsa thiazoline heterocycle and two residues of Ser and Thr with the hydroxy function modified asreverse prenyl (rPr). Cornerstones of the synthesis are as follows: (i) solid-phase peptide chainelongation using a quasi-orthogonal protecting scheme with tert-butyl and fluorenyl based groups,on a chlorotrityl resin; (ii) concourse of HOAt-based coupling reagents; and (iii) cyclizations insolution. Furthermore, the following synthetic steps are discussed: (i) preparation of the reverseprenyl derivatives of Ser and Thr; (ii) introduction of precursor of thiazoline as a protected aminothionoacid derivative; and (iii) formation of the thiazoline ring with DAST. All these features makethis strategy particularly suitable for the large-scale synthesis of trunkamide A and other peptidescontaining the same motifs.
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