Physicochemical and biochemical properties of synthetic zinc 131-(un)substituted chlorophyll-a derivatives

Zinc methyl pheophorbides a/a’, which possess oxo and methoxycarbonyl groups at the C131- and C132-positions, respectively, on the exo-five membered ring fusing the cyclic tetrapyrrole of their chlorin π-skeletons, were prepared via chemical modifications of chlorophyll a produced in phototrophs. The C131-hydroxylated and unsubstituted analogues were synthesized by reduction of the ketone moiety. The C131- and C132-stereochemistry of these semi-synthetic compounds was confirmed by 1H NMR and circular dichroism spectroscopies. A methoxycarbonyl group at the chiral C132-position in the ketone was stereo-inverted under basic conditions, whereas those in the corresponding alcoholic and dihydro-forms were not. The in vitro BciC enzymatic reaction of the (132R)-ketone was found to stereoselectively hydrolyze the C132-methoxycarbonyl group, followed by spontaneous decarboxylation. Similarly, the (132R)-COOCH3 group in the (131S)-alcohol was hydrolyzed, whereas the (132R)-COOCH3 group in the (131R)-alcohol was not. After the enzymatic reaction of the C131-dihydro-compound, its (132S)-demethoxycarbonylated and hydroxylated product was observed. [Display omitted] •Zinc 131-hydroxylated and unsubstituted chlorophyll-a derivatives were synthesized.•The 131- and 132-stereochemistry was confirmed by 1H NMR and CD spectroscopies.•The 131-oxo analog was 132-epimerized, but 131-hydroxy and dihydro forms could not.•A recombinant BciC enzyme stereospecifically hydrolyzed the 132-COOMe in vitro.