Asymmetric Total Synthesis of Naturally Occurring (-)-EBC-329 through an (E)-Selective Cross-Metathesis Reaction.

We disclose the first asymmetric synthesis of naturally occurring seco-casbene diterpene (-)-EBC-329. Lipase-mediated enzymatic enantioselective desymmetrization (EED) was employed to fix the cyclopropane-containing (8R,9S) stereocenters in the natural product. An E-selective CM (cross-metathesis) reaction was successfully employed to construct the C12-C13 olefinic unsaturation. A conjugated γ-alkylidene-butenolide, the key partner in the CM reaction, was constructed through a "Pd-Cu" bimetallic cascade cyclization reaction. Late-stage Wittig olefination was employed for the assembly of C6-C7 unsaturated acid functionality. Measurement of the optical rotation value and circular dichroism analysis confirms the absolute configuration of the natural product.