2016 Volume 74 Issue 5 Pages 426-440
Multicomponent reaction represented by Mannich reaction, Strecker reaction and Biginelli reaction has been applied to several natural product synthesis because a complexed framework of the natural product can be constructed by assembling more than three simple components at one step. It is also attractive from a medicinal chemical point of view because it enables us to supply a range of analogues to investigate a structure-activity relationship simply by changing components in the reaction. Here, we described our recent studies utilizing a multicomponent reaction in natural product-based medicinal chemistry. First topic is about total synthesis of syringolin A class of proteasome inhibitor and its structure-activity relationship study by intramolecular Ugi three-component reaction. We also synthesized cyclic peptide natural products (sandramycin, quinaldopeptin) and analogues and revealed their biological properties. Finally, design and synthesis of simplified caprazamycin analogues using aza-Prins-Ritter reaction was described.