Total Synthesis of Natural and Unnatural Lamellarins with Saturated and Unsaturated D-Rings

Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi−RC) of the benzyldihydroisoquinoline and α-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54−95% yield. In addition, only two steps in our developed strategy require column chromatography.