Stereodivergent Total Syntheses of (+)‐Mycaperoxides C, D, G Methyl Ester and (−)‐Mycaperoxide B

Mycaperoxides are natural endoperoxides isolated from different Mycale genus sponges, showing significant antiviral or antibacterial activities. We report herein the first total syntheses of representative congeners of this family from sclareol using a stereodivergent approach. Thus, an innovative oxidative ring expansion of cyclobutanol was used to bring the 1,2‐dioxane subunit, and a Mukaiyama aldol reaction on peroxycarbenium species was utilized to install the propionic acid subunit. During the study toward (+)‐mycaperoxide D methyl ester (2), the isolation of the eight possible diastereomers under their ethyl thioester form allowed to build a pertinent database for further NMR assignment studies. Thus, we completed the total syntheses of (+)‐mycaperoxides D, C, G methyl ester, and (−)‐mycaperoxide B in 11 to 15 steps, confirming their original assignment. Totally expanded. (+)‐Mycaperoxides D, C, G methyl ester, and (−)‐mycaperoxide B were synthesized in 11 to 15 steps for the first time. A stereodivergent approach from sclareol was adopted, highlighting ring expansion of strain cyclobutanol into 1,2‐dioxane, and Mukaiyama aldol reaction on peroxycarbenium species to install the propionic acid subunit.