Facile and Divergent Synthesis and Antifungal Evaluation of Drimane Meroterpenoids by Merging Decarboxylative Borylation and Suzuki Coupling
Based on the easily accessible and inexpensive sclareol, the bench stable drimanyl BPin was achieved through oxidative degradation and decarboxylative borylation. The following Suzuki coupling of the borate intermediate was developed as a powerful platform for a large variety of drimane meroterpenoids, non-natural mimics and ring-distorted motifs. Key features include mild conditions, operational facility, broad substrate scope, scalability, and good chemofidelity and stereofidelity as well as the easy availability of the various coupling partners.
formal synthesis of a large number of complex natural products is feasible via
the current methodology. The high degree of practicality of the current
chemistry bodes well for the discovery sciences towards pharmaceutically
important meroterpenoids or leads through detailed SAR study. The facile
accessibility to drimane meroterpenoids and mimics allowed the unprecedented evaluation
of these chemical entities as antifungal agents. The promising activity of the non-natural
mimics may open a new window for structural optimization and the identification
of new targets.