First Asymmetric Total Synthesis and Insight into the Structure of Laurenidificin.

Yoshikawa, Yusuke; Yamakawa, Maki; Kobayashi, Tetsuya; Murai, Kenichi; Arisawa, Mitsuhiro; Sumimoto, Michinori; Fujioka, Hiromichi

( )-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 af-forded 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.

SKELETON; ISOMERS; ETHERIFICATION; CYCLOHEXADIENONES; STEREOSELECTIVE reactions; NUCLEAR magnetic resonance spectroscopy

European Journal of Organic Chemistry, 2017, Vol 2017, Issue 19, p2715

1434-193X

Academic Journal

10.1002/ejoc.201700321