The Convergent Synthetic Efforts toward Knightol and a Simplified Analog

Abstract We report our efforts toward the convergent total synthesis of the cembranoid diterpene (−)-knightol, a marine natural product reported to exhibit antibiofilm activity against Staphylococcus aureus, and a rationally designed aryl analog, mknightol. Our strategy was guided by a two-phase approach involving construction of the macrocyclic framework, followed by selective epoxidation and further diversification. Both targets were designed to arise from common western fragment building blocks and an eastern fragment accessible on a gram scale. A scalable cross-electrophile coupling provided efficient access to an advanced intermediate en route to the cyclophane and enabled evaluation of key late-stage transformations.