抄録
Tamulamide B (1), a new family of marine polycyclic ethers, was isolated from the Florida red tide dinoflagellate Karenia brevis by Baden and co-workers in 2010. This compound inhibits the binding of tritiated dihydrobrebetoxin B to the voltage-sensitive sodium channels in a concentration dependent manner and acts as a brevetoxin antagonist. As well as the novel biological activities, the unique structural features have attracted attention of synthetic chemists. In this paper, we wish to report the recent results and our efforts on the synthetic study of tamulamide B (1). Synthesis of the ABC ring segment 3 was started from the known lactone 5. The Kumada-Tamao-Corriu coupling of the triflate 6, prepared from 5, with vinylmagnesium bromide gave the diene 7, which was converted to the acrylate 9. Reductive cyclization of 9 with SmI2 efforted 10 in highly stereoselective manner. Compound 10 was converted to the ABC ring segment 3 by several steps. The FG ring segment 4, prepared from the furan 14 via the Achmatowicz reaction and Et3SiH reduction, was connected with the ABC ring fragment 3 leading to the a-acetoxy ether 28. Intramolecular allylation of 28 followed by ring-closing metathesis using the Grubbs catalyst 30 to furnish the heptacyclic ether 2. The right hand diene was introduced by Wittig reaction, and the construction of the left hand side chain was archieved by Curtius rearrangement to afford the acetamide 38. Further studies towards the total synthesis of tamulamide B (1) is in progress.
