Tetrahydrocyclopenta [b]furanols and their derivatives are a privileged fused heterocyclic skeletons frequently found in many natural products and biologically active molecules, such as heliconol A-C, HIV-1 protease inhibitors, methyl rocaglate and rocaglamide, 3 PRMT5 inhibitors, silvestrol and episilvestrol, and so on (Figure ). These compounds exhibit a broad spectrum of important biological activities, including antifungal, anticancer, anti-inflammatory, anti-HIV and serine hydrolase inhibitory activities.