A convergent synthesis of the decacyclic ciguatoxin model containing the F-M ring framework

A highly convergent synthesis of the decacyclic ciguatoxin model 2, which c ontains the F-M ring framework of the natural product, has been achieved th rough the assembly of pentacyclic oxonane 4 and JKLM ring fragment 5. The t wo key steps in the synthesis of the former compound are (i) a Lewis acid-m ediated intramolecular reaction of a gamma-alkoxyallylsilane with an acetal group to form an O-linked oxacycle and (ii) a SmI2-mediated intramolecular Reformatsky reaction leading to construction of the annelated oxonane ring system. Preliminary biological investigations revealed that model compound 2 did not inhibit the binding of tritium-labeled dihydrobrevetoxin B to vo ltage-sensitive sodium channels at micromolar concentrations.