Total Synthesis of Racemic Laurenditerpenol, an HIF-1 Inhibitor

The convergent total synthesis of the HIF-1 inhibitor laurenditerpenol 1 and its diastereomer 1' is reported. The key step involves the Julia-Kocienski olefination-reduction process between the sulfone 55 and the aldehyde 54. The unusual trimethylated oxanorbornane sulfone 55 was successfully synthesized from the known exo Diels-Alder adduct 24 of 2,5-dimethylfuran 7 and maleic anhydride 23 in 8 steps. The aldehyde 54 was prepared by ring-opening and elaboration of lactone 41. In addition, four analogues of 1 were also successfully synthesized for biological testing.