For the planningo fa no rganic synthesis route, the disconnection approach guided by retrosynthetic analysis of possible intermediates and the chemical reactions involved, backt or eady available starting materials, is well established. In contrast, such concepts just get developed for biocatalytic routes. In this Review we highlightf unctional group interconversions catalyzed by enzymes. The article is organized rather by chemical bonds formed-exemplified for CÀN, CÀO-and CÀC-bonds-and not by enzyme classes, covering ab road range of reactions to incorporate the desired functionality in the target molecule. Furthermore, the successful use of biocatalysts, also in combination with chemicals teps, is exemplified for the synthesis of various drugs and advanced pharmaceutical intermediates such as Crispine A, Sitagliptina nd Atorvastatin. This Reviewa lso provides some basic guidelines to choose the most appropriate enzyme for at argeted reaction keepingi nm ind aspects like commercial availability,c ofactor-requirement, solventt olerance, use of isolated enzymes or whole cell recombinant microorganisms aiming to assist organic chemists in the use of enzymesf or synthetic applications.

No abstract

The development of a continuous flow process for the multistep synthesis of α-halo ketones starting from N-protected amino acids is described. The obtained α-halo ketones are chiral building blocks for the synthesis of HIV protease inhibitors, such as atazanavir and darunavir. The synthesis starts with the formation of a mixed anhydride in a first tubular reactor. The anhydride is subsequently combined with anhydrous diazomethane in a tube-in-tube reactor. The tube-in-tube reactor consists of an inner tube, made from a gas-permeable, hydrophobic material, enclosed in a thick-walled, impermeable outer tube. Diazomethane is generated in the inner tube in an aqueous medium, and anhydrous diazomethane subsequently diffuses through the permeable membrane into the outer chamber. The α-diazo ketone is produced from the mixed anhydride and diazomethane in the outer chamber, and the resulting diazo ketone is finally converted to the halo ketone with anhydrous ethereal hydrogen halide. This method eliminates the need to store, transport, or handle diazomethane and produces α-halo ketone building blocks in a multistep system without racemization in excellent yields. A fully continuous process allowed the synthesis of 1.84 g of α-chloro ketone from the respective N-protected amino acid within ~4.5 h (87% yield).

Gliflozins are an important class of prescription drugs used to treat type II diabetes. They reduce blood sugar levels by targeting the sodium-glucose transport protein 2 (SGLT2) and consequently inhibit glucose reabsorption in the kidney. There are currently several FDA-approved gliflozins as well as others in the pipeline to be launched in the next few years. This review describes the synthetic strategies used for manufacturing SGLT2 inhibitors on both bench and industrial scales. Moreover, the drawbacks to the strategies and the improvements made to obtain selected gliflozins and their glucose derivatives over the years are highlighted.

Silica immobilized lipases have been prepared and utilized in the valorization of fatty acid-derived food waste streams under continuous flow conditions. Findings demonstrate that better conversions could be obtained when compared with commercially available immobilized enzymes. † Electronic supplementary information (ESI) available. See