Explorations into neolignan biosynthesis: concise total syntheses of helicterin B, helisorin, and helisterculin A from a common intermediate.
Helicterins A and B (1 and 2), helisorin (3), and helisterculin A (4) are structurally unique natural products with the ability to combat the avian myeloblastosis virus. Biogenetically, their architectures are considered to be products of seemingly straightforward Diels-Alder, radical-based, or acid-induced dimerizations of common, simpler precursors. Yet, the pursuit of such blueprints in the laboratory has failed thus far in enabling their successful synthesis. Herein, we describe the first total syntheses of three of these natural products. Key features include the use of a building block distinct from Nature's likely starting material, highly complex retro Diels-Alder/Diels-Alder reaction cascades, an unconventional protecting group to achieve the proper balance of chemical reactivity on sensitive scaffolds, and several carefully developed reaction conditions that effectively balance competing reaction pathways.
Snyder
Scott A
SA
Department of Chemistry, Columbia University, Havemeyer Hall, 3000 Broadway, New York, New York 10027, USA.
Kontes
Ferenc
F
D002934:Cinnamates / Q000737:chemistry; D053630:Depsides / Q000737:chemistry; D017705:Lignans / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry; D019660:Malvaceae / Q000737:chemistry / Q000378:metabolism; D000097123:Rosmarinic Acid
D002934:Cinnamates; D053630:Depsides; D017705:Lignans; D000097123:Rosmarinic Acid