Functionalized tetrahydrofurans (THFs) constitute key structural features of biologically interesting natural products exhibiting significant various pharmacological activities including anticancer, antiviral, antibiotic and antifungal activities (Figure 1). In particular, 2,5-cis- or -trans disubstituted-THFs are found in a wide range of complex natural products which have been largely attracted from synthetic community culminating the development of a number of methodologies.
The total synthesis of proposed (−)-bisezakyne A and revised (−)-bisezakyne A have been accomplished in 15 steps for longest sequence from commercially available hexa-1,5-dien-3-ol with an overall yields of 6.8% and 3.7%, respectively. Highlight of the synthesis include the IAEA (intramolecular amide enolate alkylation) for steroselective synthesis of 2,3-cis-2,5-cis-tetrahydrofuran and 2,3-cis-2,5-trans-tetrahydrofuran and the Nakata’s halogenation protocol. In addition, our synthesis unambiguously confirmed the absolute configuration of the natural (−)-bisezakyne A.
