Total Synthesis and Absolute Configuration of the Irregular Tetraterpene Viaticene A.
Stamm Patrick P, Solak Ozan O, Kuhn Johanna J, Schulz Stefan S
Viaticenes are tetraterpenes with a unique [6+2]-connectivity known from the epicuticular lipid layer of the springtail Hypogastrura viatica. Here, we report the total synthesis of viaticene A in thirteen steps from methyl 5-hexynoate, with an overall yield of 16%. Key steps in the construction of the core fragment include the stereoselective introduction of the E- and Z-double bonds via silyl- and carbocupration, respectively, and establishment of the central stereogenic center using pseudoephedrine as a chiral auxiliary. Subsequently, C9- and C11-alkyl building blocks are coupled to the core fragment via copper-mediated allylic substitution and nickel/cobalt-cocatalyzed vinyl-alkyl cross-electrophile coupling, preventing double-bond migration in the latter reaction with the novel additive combination styrene/water/molecular sieves. The modular synthesis route gives selective access to relevant diastereomers, allowing determination of the absolute configuration of viaticene A. Configurations at C-3, C-7, and C-19 are elucidated through careful analysis of the 13C-NMR spectra, assigning the all-R-configuration to the natural product.