Exploring Short and Efficient Synthetic Routes Using Titanocene(III)-Catalyzed Reactions: Total Synthesis of Natural Meroterpenes with Trisubstituted Unsaturations.

The stereo- and regioselective total syntheses of OMe derivatives of the scarce bioactive meroterpenoids makassaric acid () and fascioquinol B () have been accomplished. The synthetic sequences are based on the following three efficient and selective catalytic reactions: Cu-catalyzed addition of Grignard compounds to an epoxide; a regioselective Barbier-type reaction, catalyzed by CpTiCl; and regio- and stereoselective bioinspired cyclization, also catalyzed by CpTiCl. These three key processes allow us to obtain the main skeletons of and in a few steps. The valuable synthetic proposal shown in this work provides fast access to scarce, structurally complex meroterpenes with promising biological activities, which are a sustainable source for later studies and applications in medicine.