Synthesis and Studies of NADH Models: Stereoselective Reductions and Host-Guest Properties

Sammanfattning: The aim of the project has been to synthesise macrocyclic NADH models and to study them as reducing agents and hosts. Three types of macrocyclic NADH models have been synthesised. They consist of the same subunits; a chiral unit, a nicotinamide unit and an aromatic spacer. Several nicotinamide units are incorporated in the models, thus creating multicentre redox systems. The macrocyclic framework with aromatic spacers forms a chiral, hydrophobic cavity suitable for complexation of certain substrates.

The first two models that were studied were prepared in a similar fashion. Their host-guest properties in water were then investigated. Both models showed an affinity for benzoic acid derivatives such as the dianions of terephthalic (TP^2-) and isophthalic acid (IP^2-). In the 1:1 complex between the larger of the two models and TP^2- and IP^2-, respectively, it was shown that the guests were located inside the cavity.

These two models were also tested as reducing agents in methylene chloride using Mg²⁺ as a cocatalyst. Both compounds were able to reduce methyl benzoylformate stereoselectively in good yields. Reductions using the smaller model were more selective, where reduction of ethyl benzoylformate to ethyl mandelate gave as high as 96 % enantiomeric excess. A third type of NADH model was designed, for which a synthetic route was developed. This model was also capable to stereoselectively reduce methyl benzoylformate in methylene chloride. Using the developed synthetic route, a water-soluble reducing agent can be prepared. Such a model has the potential to reduce substrates catalytically and stereoselectively in water.