Bioinspired Collective Synthesis of Gymnothelignans I, F, K, and L

We report a collective stereoselective synthesis of gymnothelignan members, i.e., gymnothelignans I, F, K, and L, based on their proposed biosynthetic pathways. A chiral eupomatilone skeleton was employed as a key common intermediate. Reduction of a carbonyl moiety of eupomatilone readily gave gymnothelignan I, which was smoothly converted to the corresponding oxocarbenium ion upon treatment with an acid. Subsequent intermolecular and intramolecular nucleophilic additions of respective nucleophiles to the oxocarbenium ion provided gymnothelignans F, K, and L. This work provides information to support the plausible biosynthetic pathway of these structurally unique lignans.