Marine furanocembranoids-inspired macrocycles enabled by Pd-catalyzed unactivated C(sp3)-H olefination mediated by donor/donor carbenes

Abstract Biomimetic modularization and function-oriented synthesis of structurally diversified natural product-like macrocycles in a step-economical fashion is highly desirable. Inspired by marine furanocembranoids, herein, we synthesize diverse alkenes substituted furan-embedded macrolactams via modular biomimetic assembly strategy. The success this the development crucial Pd-catalyzed carbene coupling between ene-yne-ketones as donor/donor precursors unactivated Csp 3 ?H bonds which represents great challenge organic synthesis. Notably, method not only obviates use unstable, explosive, toxic diazo compounds, but also can be amenable to allenyl ketones precursors. DFT calculations demonstrate that formal 1,4-Pd shift could involved mechanism. Moreover, collected furanocembranoids-like show significant anti-inflammatory activities against TNF-?, IL-6, IL-1? cytotoxicity comparable Dexamethasone.