Total synthesis and structural confirmation of the antibacterial diterpene leubethanol

We report the total synthesis of leubethanol (1), a serrulatane compound that has recently been reported as having considerable antibacterial activity against multidrug-resistant bacteria, such as Staphylococcus aureus, and is of interest for applications in the control of bacterial biofilms in human medicine. Our synthetic route begins with (-)-isopulegol (4) and key steps include substrate directed hydroboration to generate the C1′ stereocentre and formation of the aromatic ring via the α-oxoketene-S,S-acetal intermediate 3. Overall the conversion of (-)-isopulegol (4) to leubethanol was achieved in 13 steps and an overall yield of 7%. Comparison of our spectroscopic data with those reported for leubethanol (1), isolated from Leucophyllum frutescens, verified the structure of the natural product.