title: The Evolution of the Total Synthesis of Rocaglamide.
abstract: The complex flavagline, (-)-rocaglamide, possesses a synthetically intriguing tricyclic scaffold with five contiguous stereocenters and also exhibits potent anticancer, anti-inflammatory and insecticidal activity. This full account details distinct approaches to (±)- and (-)-rocaglamide utilizing Brønsted acid catalyzed and asymmetric Pd0-catalyzed Nazarov chemistry developed in our laboratory, respectively. The successful asymmetric synthesis revealed unforeseen mechanistic complexity that required adjusting our strategy to overcome an unanticipated racemization process, an unusual reversible ring-cleavage step and a very facile trialkylsilyl group migration.
authors.affiliation: Chemistry Department, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI, 96822, USA.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Chemistry Department, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI, 96822, USA.
authors.forename: Darryl D
authors.initials: DD
authors.lastname: Dixon
authors.affiliation: Chemistry Department, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI, 96822, USA.
authors.forename: Anais
authors.initials: A
authors.lastname: Jolit
authors.affiliation: Chemistry Department, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI, 96822, USA. tius@hawaii.edu.|University of Hawaii, Cancer Center, 701 Ilalo Street, Honolulu, HI, 96813, USA. tius@hawaii.edu.
authors.forename: Marcus A
authors.identifier: http://orcid.org/0000-0002-7092-8993
authors.initials: MA
authors.lastname: Tius
mesh_terms: D000143:Acids / Q000737:chemistry*; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D003500:Cyclization; D010165:Palladium / Q000737:chemistry*
chemical_list: D000143:Acids; D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D010165:Palladium; C107772:rocaglamide
keywords: Nazarov; cyclization; palladium catalysis; rocaglamide; total synthesis