Total Synthesis of Gambierol, a Marine Polycyclic Ether

Abstract

The first total synthesis of gambierol, a marine polycyclic ether toxin, has been achieved. Highly efficient synthesis of the ABC and EFGH ring fragments allowed us to prepare those two advanced intermediates in multi-gram quantities. The key feature of the present total synthesis is the B-alkyl Suzuki-Miyaura coupling tactics, which culminated in the union of the advanced intermediates and convergent synthesis of the octacyclic polyether core. Introduction of the sensitive triene side chain via Pd(PPh3) 4/CuCl/LiCl-promoted Stille coupling was conducted at the final step of the synthesis. The present total synthesis supplied useful quantities of gambierol and its structural analogues for detailed biological studies: an interesting observation was gained through pathological studies. Also, preliminary structure-activity relationship studies revealed that the functionalities present in the H ring and unsaturated side chain are crucial for notent toxicitv asainst mice.