Total Synthesis of Keramaphidin B and Ingenamine

The full details of the total synthesis of keramaphidin B and ingenamine are reported. The most conspicuous transformation in our total synthesis is the base-catalyzed Diels-Alder reaction using dynamic regioselective crystallization (alternatively referred to as crystallizationinduced transformation: CIT). The tertiary alcohol, which is used for the base-catalyzed activation in the Diels-Alder reaction, is removed as its p-fluorobenzoate using SmI 2 (HMPA) 4 . Double macrocyclic alkylation enables the regioselective construction of two macrocycles in a single step. The developed sequence is highly efficient, achieving the unified total synthesis of keramaphidin B and ingenamine within 13 steps from commercially available compounds. Our biological study elucidated the significant role of the two macrocycles in their antiproliferative effects against human cancer cell lines.