Photodecarboxylative Ring Annulation of α- and β-Functionalized Phthaloyl-GABA Derivatives : (Bioactive Pyrroloisoindolinones with High Quantum Efficiency)

The triplet-sensitized (by the solvent acetone) as well as the direct (λₑₓ=300–320 nm) photochemical decarboxylation of N-phthaloylated γ-aminobutyric acid (GABA) derivatives are versatile and high-yielding routes to benzopyrrolizidines via intramolecular electron transfer initiated decarboxylation followed by radical coupling. The ß-mono- and ß,ß'-disubstituted N-phthaloyl GABA derivatives 7 a–7 g, respectively, were applied as substrates. Decarboxylative photocyclization yielded hydroxy benzopyrrolizidines 8 a–8 g in high chemical yields and with moderate diastereoselectivities from the ß-monosubstituted substrates. The analogous α-substituted GABA derivatives 11 a–11 c were also applied as potential substrates for memory of chirality effects. The reaction quantum yields of the photodecarboxylation reactions for the parent GABA derivative 13 and for the new substrates 7 h and 11 a were determined by the quantum yield determination system (QYDS) and showed a remarkable concentration dependency indicating aggregation at higher substrate concentrations. Inhibition studies on the atherogenic human serine hydrolase cholesterol esterase showed derivatives 8 a and 8 d to exhibit a hyperbolic mode of inhibition with moderate IC₅₀ values of about 60–80 μM.