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

Autor:	Rand AW; Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States., Gonzalez KJ; Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States., Reimann CE; Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States., Virgil SC; Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States., Stoltz BM; Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
Jazyk:	angličtina
Zdroj:	Journal of the American Chemical Society [J Am Chem Soc] 2023 Apr 05; Vol. 145 (13), pp. 7278-7287. Date of Electronic Publication: 2023 Mar 23.
DOI:	10.1021/jacs.2c13146
Abstrakt:	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.
Databáze:	MEDLINE
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