Metal-Free, One-Pot Cascade Annulation of 2-Pyrones in Water for the Synthesis of Peptidomimetics.

A one-pot, metal-free, double cyclization for the synthesis of bicyclic 2-pyridones as peptidomimetics was developed. In this process, the transformation of 2-pyrones bearing a tethered, homochiral α-amino acid started with the removal of the N-Boc protective group under acidic or neutral conditions at elevated temperature, followed by several key transformations, including cyclic enamine formation, decarboxylation or esterification, isomerization, and lactamization, to furnish bicyclic 2-pyridones in up to 98% yield with retention of the chirality at the α-carbon of the amino acid portion of the molecule. Exploration of the substrate scope revealed some selectivity between the decarboxylation and esterification pathways under thermal acidic conditions, while performing the reaction in boiling water yielded the decarboxylation products exclusively.

Citation

Wannaporn Disadee, Anek Lekky, Somsak Ruchirawat. Metal-Free, One-Pot Cascade Annulation of 2-Pyrones in Water for the Synthesis of Peptidomimetics. The Journal of organic chemistry. 2020 Feb 21;85(4):1802-1822

Mesh Tags

Substances

PMID: 31875399

search → result