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The Evolution of the Total Synthesis of Rocaglamide
Zhe Zhou1, Darryl D Dixon1, Anais Jolit1
1Chemistry Department, University of Hawaii at Manoa, 2545 The Mall, Honolulu, HI, 96822, USA.
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.
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