Lipases - Enzymes for biocatalytic asymmetric synthesis

Abstract

(A) Kinetic resolution of racemates is the most common application for lipases in organic synthesis, and there are countless examples of successful attempts to separate enantiomers with a free hydroxyl residing not too far from the stereogenic center. The ee values are short of astonishing in many cases, and Upases are therefore very useful in the preparation of chiral synthons. Enantiomers of C4 building blocks featuring a dithiane and an oxirane were constructed by Sundby et al., with a lipase-catalyzed kinetic resolution as a key step. (B) Integration of lipase-catalyzed kinetic resolution into a reaction sequence may be a rewarding solution in cases where stereo-selective synthesis is unavailable or fails. Kamal et al. have developed a one-pot synthesis of enantiopure secondary alcohols from carbonyl compounds by tandem reduction-resolution. The method was applied in a chemoenzymatic synthesis of both enantiomers of the β-adrenoreceptor blocker propranolol (1) in excellent yields and optical purities. (C) Yamagishi et al. reported a lipase-catalyzed kinetic resolution of α-hydroxy-H-phosphinates. With two chiral centers, one on phosphorus and one on the adjacent carbon, the substrate comprised a mixture of diastereomers. The lipase hydrolyzed the acetate of only one diastereomer in the mixture stereoselectively with very high preference, yielding one enantiomer in excellent ee. (D) Lipases have become important tools for regio- and stereoselective protection and deprotection of carbohydrates. In a study on regioselective acylation of pyranoses, Gonçalves et al. unveiled enzymatic means for the resolution of α and β-anomers of galactose derivatives. Both anomers were acylated in position 6, while the β-anomer reacted also on position 2. (E) While kinetic resolution offers a maximum yield of 50% of one enantiomer, dynamic kinetic resolution (DKR) may realize higher yields of the desired enantiopure compound by constant racemization of the substrate in situ. Protocols for chemoenzymatic DKR of different substrates employing a metal catalyst for racemization and an immobilized lipase have been developed by Bäckvall and co-workers. Recently, a highly efficient method for DKR of alcohols was reported. (F) Lipase-catalyzed enantioselective desymmetrization can afford optically active compounds in high yields since all of the substrate can be utilized in a symmetry-breaking reaction. In pursuit of axially chiral biaryls, Matsumoto et al. applied lipases to stereoselectively hydrolyze σ-symmetric biaryl diacetates. (G) Desymmetrization of prochiral diols affords enantiomerically enriched mono-esters. 2-Functionalized 1,3-propanediols are useful starting materials for asymmetric acetylation with lipases, yielding products that can be further transformed with chemoselectivity. Neri and Williams used lipases to desymmetrize N-Boc-serinol, and converted the product further into chiral Evans auxiliaries. © Georg Thieme Verlag Stuttgart.