Challenges in the Syntheses of Peptidic Natural Products

Abstract

Peptidic natural products are commonly perceived as ‘simple’ molecules that are easily accessible by standard methods. This review sets out to demonstrate that the total synthesis of peptidic natural products is far from being ‘standard’ and highly elaborate methodologies paired with careful synthesis planning are required to attain their often complex structures. 1 Introduction 2 Peptide Synthesis with Amino Acids Incompatible with ‘Standard’ Peptide Synthesis Conditions: The Synthesis of Feglymycin and Tubulysin D 3 Macrocyclizations as Pitfalls in the Synthesis of Cyclo(depsi)peptides: The Synthesis of Largazole 4 Synthesis of Cyclo(depsi)peptides via Carbon–Carbon Bond-Forming Macrocyclizations: The Synthesis of Chondramide C and Syringolin A 5 Control of Atropisomerism in Side-Chain-Cyclized Peptidic Natural Products: The Synthesis of Chloropeptin, Complestatin (Chloropeptin II) and Isocomplestatin 6 Solid-Phase Syntheses of Peptidic Natural Products: The Synthesis of Oxathiocoraline and Symplocamide A 7 Structural Complexity as a Challenge: The Synthesis of Kapakahines 8 Conclusions