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

• Autoři: THARRA Prabhakara Rao; MIKHAYLOV Andrey; ŠVEJKAR Jiří; GYSIN Marina; HOBBIE Sven N.; ŠVENDA Jakub
• Rok publikování: 2022
• Druh: Článek v odborném periodiku
• Časopis / Zdroj: Angewandte Chemie International Edition
• Fakulta / Pracoviště MU: Přírodovědecká fakulta
• www: https://onlinelibrary.wiley.com/doi/full/10.1002/anie.202116520
• Doi: https://doi.org/10.1002/anie.202116520
• Klíčová slova: Antibiotics; Natural Products; Organic Synthesis; Radical Chemistry; Ribosome Inhibitors
• Popis: 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.

Související projekty

• Postdoc@MUNI
• Preklinická progrese nových organických sloučenin s cílenou biologickou aktivitou
• Syntéza a biologické testování analogů přírodních antibiotik bactobolinů