Total Synthesis of Rhizopodin Enabled by a Late-Stage Oxazole Ring Formation Strategy
Junyang Liu1,2, Kai Chen2, Yian Guo2
1School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, 529020, China.
Abstract:
Actin stabilizers that are capable of interfering with actin cytoskeleton dynamics play an important role in chemical biology. Rhizopodin, a novel actin stabilizer, affects the actin cytoskeleton at nanomolar concentrations and exhibits potent antiproliferative activities against a range of tumor cell lines with IC50 values in the low nanomolar range. Herein, we report the total synthesis of rhizopodin based on a late-stage oxazole ring formation strategy, whose success demonstrates the feasibility of late-stage oxazole ring formation in the synthesis of complex oxazole containing natural products. Other features of the synthesis include a Nagao aldol reaction, a Suzuki coupling, a Yamaguchi esterification, a modified Robinson-Gabriel synthesis of the oxazoles, and a bidirectional Ba(OH)2-mediated Horner-Wadsworth-Emmons (HWE) reaction.
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