Stereocontrolled Synthesis of (−)-Bactobolin A

A stereoselective synthesis of the ribosome-binding antitumor antibiotic (−)-bactobolin A is reported. The presented approach makes effective use of (−)-quinic acid as a chiral pool starting material and substrate stereocontrol to establish the five contiguous stereocenters of (−)-bactobolin A. The...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2020-04, Vol.142 (16), p.7306-7311
Main Authors: Vojáčková, Petra, Michalska, Lucyna, Nečas, Marek, Shcherbakov, Dimitri, Böttger, Erik C, Šponer, Jiří, Šponer, Judit E, Švenda, Jakub
Format: Article
Language:English
Subjects:
Benzopyrans - chemical synthesis
Catalysis
Stereoisomerism
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Summary:A stereoselective synthesis of the ribosome-binding antitumor antibiotic (−)-bactobolin A is reported. The presented approach makes effective use of (−)-quinic acid as a chiral pool starting material and substrate stereocontrol to establish the five contiguous stereocenters of (−)-bactobolin A. The key steps of the synthesis include a stereoselective vinylogous aldol reaction to introduce the unusual dichloromethyl substituent, a completely diastereoselective rhodium­(II)-catalyzed C–H amination reaction to set the configuration of the axial amine, and an intramolecular alkoxycarbonylation to build the bicyclic lactone framework. The developed synthetic route was used to prepare 90 mg of (−)-bactobolin A trifluoroacetate in 10% overall yield.
ISSN:0002-7863
1520-5126
DOI:10.1021/jacs.0c01554