Stereoselective Construction of 2,7-Disubstituted fused-Bis Tetrahydrofuran Skeletons: Biomimetic-Type Synthesis and Biological Evaluation of (±)- and (−)-Aplysiallene and Their Derivatives

A series of trans/trans and cis/cis fused-bis tetrahydrofuran compounds have been obtained stereoselectively in high yields via a one-pot operation involving the intramolecular haloetherification of (Z,Z)-diene diol 19a and (E,E)-diene disilylether 19d, respectively. This method was subsequently applied to the biomimetic-type synthesis of (±)- and (−)-aplysiallene. The inhibitory activities of these compounds and their bromodiene isomers toward Na+/K+ ATPase were determined in vitro, and gave IC50 values of approximately 15 μM in all cases.