Amorphous zirconium metal-organic frameworks assembled from mixed porphyrins as solvent-free catalysts for Knoevenagel condensation.

Three mixed porphyrins, icpp (1-3), were synthesized via the reactions of 4-formylbenzoic acid and 4-imidazolecarboxaldehyde, and then five amorphous or crystalline Zr-MOFs-SPUZ (1-5) were obtained from icpp (1-3), timp and tcpp, respectively. The catalytic activities of the synthesized porphyrins and MOFs were studied on the Knoevenagel condensation of aldehydes and malononitrile under solvent-free conditions. Among them, amorphous MOF SPUZ-1 showed the highest catalytic activity. Further studies on various aldehydes demonstrated that most reactions were completed with a low catalyst loading (1 mol%) in a short reaction time (5-30 min), and the best result was obtained with the yield of 99.9% within 5 min. Moreover, SPUZ-1 could be recycled 7 times without significant loss of activity.

Enantioselective bioreduction of benzo-fused cyclic ketones with engineered Candida glabrata ketoreductase 1 - a promising synthetic route to ladostigil (TV3326).

Biocatalysis has been recently emerging as a promising alternative to traditional chemical synthesis because of its "green" characteristics and comparable selectivities, which accord with the concept of sustainable development and demand for asymmetric synthesis. In this study, whole-cell biocatalysts containing glucose dehydrogenase (GDH) and Candida glabrata ketoreductase 1 (CgKR1) variants were constructed. These biocatalysts were applied to the reduction of benzo-fused cyclic ketones and showed good to high activities and enantioselectivities. Particularly, CgKR1 variants displayed high activities (90.6%-98.4% conversions) and enantioselectivities (>99.9% ee) towards 5a, a key intermediate of ladostigil (TV3326). Based on these results, a chemoenzymatic synthesis of (S)-5b was developed by using biocatalytic asymmetric reduction as a key step, giving the product with a total yield of 34.0% and 99.9% ee.