Organocatalyst for Regioselective Lactonization

Keywords

aminoxyl-peptides - organocatalyst - regioselective lactonization

Significance

Lactones are prominent functional groups in synthesis, appearing in a plethora of natural product and pharmaceutical scaffolds. In this work, the authors show that asymmetric diols can be oxidatively lactonized in a regioselective manner using optimized aminoxyl-peptide catalysts. The regioselectivity of the oxidation could be controlled by the choice of organocatalyst. This is an innovative synthetic tool that invites unsymmetrical diols as useful substrates for regioselective lactonization transformations.

Comment

Using aminoxyl-peptide catalysts 1 and 2 the authors establish selective lactonization conditions for unsymmetric diols. Interestingly, lower oxidation states like hemiacetals and 1,6-hydroxyaldehydes can also be accessed by reducing the equivalents of the oxidant trichloroisocyanuric acid (TCCA). This protocol works on natural product scaffolds derived from polygodial and camphor. Another advantage of this protocol is a convenient two-step lactone transposition which was demonstrated on iridomymecin. This is not only synthetically convenient but also opens the door to late-stage drug modifications on lactone moieties.

Publication History

Article published online:
22 April 2025