First Asymmetric Total Synthesis and Insight into the Structure of Laurenidificin

Abstract

(+)‐Laurenidificin has a fused bis‐THF skeleton and an enyne structure in its side chain. It is known that the bis‐THF skeleton is cis,cis fused, and the absolute configuration at the C6 position is R, but the whole structure has not been determined. We synthesized one possible isomer of (+)‐laurenidificin by using intramolecular double bromoetherification as a key step. Treatment of a protected (E,E)‐diene diol with 2,4,4,6‐tetrabromo‐2,5‐cyclohexadienone as the halogenating agent afforded a cis,cis‐fused bis‐THF derivative in good yield with high stereoselectivity. Several additional transformations, including introduction of a hydroxy group at the C6 position and construction of the enyne structure, gave a possible isomer of (+)‐laurenidificin. The 1H NMR and 13C NMR spectroscopy data of this isomer are in complete agreement with those of natural (+)‐laurenidificin, and its optical rotation and that of natural laurenidificin have the same positive sign.