Contra-thermodynamic E → Z isomerization of cinnamamides via selective energy transfer catalysis

A bio-inspired, photocatalytic E -> Z isomerization of cinnamides is reported using inexpensive (-)-riboflavin (vitamin B-2) under irradiation at lambda = 402 nm. This operationally simple transformation is compatible with a range of amide derivatives including -NR2, -NHSO2R and N(Boc)(2) (up to 99:1 Z:E). Selective energy transfer from the excited state photocatalyst to the starting E-isomer ensures that directionality is achieved: The analogous process with the Z-isomer is inefficient due to developing allylic strain causing chromophore deconjugation. This is supported by X-ray analysis and Stern-Volmer photo-quenching studies. Preliminary validation of the method in manipulating the conformation of a simple model Leu-enkephalin penta-peptide is disclosed via the incorporation of a cinnamamide-based amino acid. (C) 2020 Published by Elsevier Ltd.