Total Synthesis of (−) and (+)-Zingibergingerols A

The first total synthesis of both of the enantiomers
of Zingibergingerol
A has been accomplished. The distinctive 3,7,9-trioxabicyclo[4.2.1]nonane
skeleton is crafted through gold-catalyzed alkynol cycloisomerization.
The synthesis comprises sequential C–C bond formations at both
ends of epichlorohydrin: first opening the epoxide with eugenol-derived
alkyne, followed by subsequent epoxide installation, and again opening
with a Grignard reagent. The resulting alkynol with a fixed C5 stereochemistry
was subjected to O-allylation, followed by dihydroxylation and alkynol
cycloisomerization.