Organocatalyst-controlled stereoselective head-to-tail macrocyclizations

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Source: Science Magazine

Original: https://www.science.org/doi/abs/10.1126/science.aec8992?af=R...

Published: 2026-02-26T07:00:02Z

Scientists have developed a new peptide-based catalyst that enables more efficient production of macrocycles – large molecular rings with 12 to 18 atoms[1]. This method uses a bifunctional peptide catalyst to direct the ends of a linear precursor, favoring ring formation instead of unwanted side reactions[1]. The catalyst controls the stereoselectivity – that is, which of the two possible mirror configurations is formed – even in cases where the linear precursor contains pre-existing stereochemical properties[1]. Scientists have synthesized diverse macrocyclic lactones and lactams from achiral linear precursors[1]. This new method provides a more practical approach to the production of chiral macrocycles with predictable stereochemical results[1]. Macrocycles have potential in new drug discovery because they can bind to large, flat or flexible protein surfaces that are inaccessible to traditional small molecules[5].