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Published April 5, 2023 | public
Journal Article

Total Synthesis of Strempeliopidine and Non-Natural Stereoisomers through a Convergent Petasis Borono-Mannich Reaction


Strempeliopidine is a member of the monoterpenoid bisindole alkaloid family, a class of natural products that have been shown to elicit an array of biological responses including modulating protein–protein interactions in human cancer cells. Our synthesis of strempeliopidine leverages palladium-catalyzed decarboxylative asymmetric allylic alkylations to install the requisite all-carbon quaternary centers found in each of the two monomeric natural products, aspidospermidine and eburnamine. Initial studies employing Suzuki–Miyaura cross-coupling followed by diastereoselective hydrogenation provided evidence for a structural reassignment of the natural product. Our final synthetic sequence employs a diastereoselective Petasis borono–Mannich reaction to couple eburnamine to a trifluoroborate aspidospermidine derivative. These convergent approaches enabled the synthesis of eight diastereomers of this heterodimer and offer support for the reassignment of the absolute configuration of strempeliopidine.

Additional Information

© 2023 American Chemical Society. The authors thank Dr. David VanderVelde for assistance with NMR experiments and Dr. Michael Takase for assistance with X-ray analysis. The authors thank the NIH-NIGMS (R35GM145239 and R01GM080269), The Merkin Institute for Translational Research, and The Heritage Medical Research Investigation Program for financial support. K.J.G. thanks the NSF GRFP for funding. The authors declare no competing financial interest.

Additional details

September 28, 2023
October 24, 2023