Facile and Divergent Synthesis and Antifungal Evaluation of Drimane Meroterpenoids by Merging Decarboxylative Borylation and Suzuki Coupling

Abstract

<p> </p><p>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.</p><p> </p><p>Expedient formal synthesis of a large number of complex natural products is feasible <i>via</i> 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.<br></p>

Modular Synthesis of Drimane Meroterpenoids Leveraging Decarboxylative Borylation and Suzuki Coupling

“…In summary, with the invention of the bench stable and easily accessible drimanyl Bpin from the inexpensive natural diterpene sclareol, a new paradigm merging decarboxylative borylation and Suzuki coupling was developed as a powerful platform for a large variety of drimane meroterpenoids and non-natural mimics. 23 The high degree of practicality bodes well for the discovery of pharmaceutically important meroterpenoids. The current facile chemistry allowed the unprecedented antifungal evaluation of these scaffolds.…”