Bioinspired Divergent Synthesis of Tricyclic Sesquiterpenoids: Cedrane, Angular Triquinane, allo-Cedrane, and Zizaene

The cedrane-, angular triquinane-, allo-cedrane-, and zizaene-type natural products belong to the classic family of tricyclic sesquiterpenoids, and many of them possess highly complex molecular structures and display interesting biological activities. Herein, we report a unified strategy toward divergent and bioinspired syntheses of these four types of tricyclic sesquiterpenoid skeletons from common advanced intermediate cyclopentenone 12, which could be constructed by reductive oxy-Nazarov cyclization. Key late-stage transformations include (i) double Brown hydroboration and oxidation, followed by an intramolecular aldol condensation to form the cedrane (I) and angular triquinane (II) skeletons, and (ii) an effective anionic semipinacol rearrangement of tricyclic cedrane mesylate (derived from cis-diol 25 and trans-diol 30) to afford allo-cedrane (III) and zizaene (IV) skeletons, not only a pathway consistent with our proposal for the biogenesis between cedrane and zizaene sesquiterpenoids but also further evidence for the biogenetic relationship between the typical cedrane and allo-cedrane sesquiterpenoids.