Novel biomimetic organocatalysts and asymmetric formal cycloaddition reactions using enolisable anhydrides as nucleophiles

Abstract

The synthesis of a biomimetic organocatalyst bearing functional groups mimicking the active residues in the active site of the oxidoreductase enzyme non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (GAPN) has been undertaken. Analogues of GAPN having a Cys-mimicking thiol group, a Asn- mimicking amide functionality but devoid of a NAD+ -mimicking pyridinium ion were prepared and evaluated in the reaction with aldehydes to form hemithioacetal species, which is the first step of the overall oxidation reaction catalysed by the natural enzyme GAPN. For the first time the reactivity of a Cys-mimicking thiol group was exploited in a biomimetic oxidation and we could observe that in our enzyme mimics, acid catalysis (in the form of hydrogenbond donation) was not involved in the hemithioacetal-forming step. Attempts to imitate the hydride transfer step of the biochemical pathway failed repeatedly due to the instability of the enzyme mimic under the reaction conditions.