Total Synthesis of Immunosuppressive Mycestericin E and G Enabled by a Highly Stereoselective Nitroso–Ene Cyclization

This report describes a streamlined synthesis of immunosuppressive mycestericin E and G through a highly stereoselective nitroso–ene cyclization in 11–12 steps using readily available materials. The stereochemical outcome in the formation of a Nα-quaternary stereogenic center is rationalized by a trajectory based on the polar diradical intermediate and subsequent hydrogen transfer. Julia olefination offers a facile chain elongation method that presents a viable strategy for structural derivatization in future medicinal applications.