Asymmetric Total Synthesis of (−)-4-Hydroxyzinowol, a Highly Oxygenated Dihydro-β-Agarofuran

Abstract

(−)-4-Hydroxyzinowol (1) is a potent inhibitor of P-glycoprotein, which has been implicated in multi-drug resistance in the treatment of cancer. The highly oxygenated structure of 1, comprising a trans-decalin AB-ring and a tetrahydrofuran C-ring, with six acyloxy groups and one hydroxy group has posed a formidable synthetic challenge. We achieved the total synthesis of this extremely complex structure in 36 steps from 5-acetoxynaphthalen-1-ol. Here our efforts to complete the total synthesis of 1 are described in detail.