Total Syntheses of (−)-Spirooliganones A and B and Their Diastereoisomers: Absolute Stereochemistry and Inhibitory Activity against Coxsackie Virus B3

To investigate the effects of configuration on bioactivity, spirooliganones A and B and their six diastereoisomers (<b>1</b>–<b>8</b>) were synthesized in 11 steps. The key benzopyran core was assembled by intermolecular [4 + 2] hetero-Diels–Alder cycloaddition between (−)-sabinene and <i>o</i>-quinone methide, which was generated from the corresponding <i>o</i>-hydroxybenzyl alcohol. After establishing the absolute configuration, the inhibitory activities of spirooliganones <b>1</b>–<b>8</b> against Coxsackie virus B3 were evaluated, and the primary structure–activity relationships were analyzed. Compound <b>3</b> was the most potent compound, with an IC₅₀ of 0.41 μM