Atroposelective Total Synthesis of Cihunamide B.

Abstract

A short, atroposelective synthesis of cihunamide B (1) is reported. The feature of this report is the decagram-scale SNAr reaction of l-tryptophan derivatives, followed by atroposelective Larock macrocyclization. This strategy allowed the construction of a Trp-Trp cross-linkage with unprecedented atropisomerism. The atroposelectivity of this Larock macrocyclization has been investigated through a combination of experimental and computational chemistry, yielding detailed insights into the synthesis of biaryl linkages. It also enabled the concise synthesis of cihunamide B (1), which is expected to be a potential antibacterial agent.