Short Synthesis of (+)-Actinobolin: Simple Entry to Complex Small-Molecule Inhibitors of Protein Synthesis

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Authors	THARRA Prabhakara Rao MIKHAYLOV Andrey ŠVEJKAR Jiří GYSIN Marina HOBBIE Sven N. ŠVENDA Jakub
Year of publication	2022
Type	Article in Periodical
Magazine / Source	Angewandte Chemie International Edition
MU Faculty or unit	Faculty of Science
Citation
web	https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202116520
Doi	https://doi.org/10.1002/anie.202116520
Keywords	Antibiotics; Natural Products; Organic Synthesis; Radical Chemistry; Ribosome Inhibitors
Description	We report a concise synthesis of the naturally occurring protein synthesis inhibitor (+)-actinobolin (1). The densely functionalized and stereochemically complex molecular structure of 1 was assembled from (-)-quinic acid, L-threonine, and L-alanine as the principal components. Our route is based around a convergent strategy that features conjugate addition of an alpha-amino radical in the key fragment-coupling step. The dramatically simplified synthesis of (+)-actinobolin proceeding in 9 steps with 18 % overall yield has practical implications for analog preparation, as demonstrated herein.
Related projects:	Postdoc@MUNI Preclinical Progression of New Organic Compounds with Targeted Biological Activity Syntéza a biologické testování analogů přírodních antibiotik bactobolinů