Читать книгу Enzyme-Based Organic Synthesis - Cheanyeh Cheng - Страница 31

Baeyer–Villiger (BV) oxidation of ketones is the insertion of a molecular oxygen into the Baeyer–Villiger monooxygenases (BVMOs) [109–111]. BVMO catalyzes the carbonyl group in a compound to form esters, or lactones, from ketones, often with great enantioselectivity [112]. It has been used as an intermediate step for the production of 11‐hydroxyundec‐9‐enoic acid, a precursor for synthesizing Nylon‐11, from ricinoleic acid via recombinant E. coli (Scheme 2.26) [113]. A variety of secondary metabolites of plants, oxygenated unsaturated carboxylic acids, which are difficult to synthesize were also explored by designing an artificial biotransformation pathway consisting of fatty acid double‐bond hydratases, ADHs, BVMOs, and esterases. In this case, γ‐linolenic acid that contains three double bonds in the carbon skeleton has been used as the substrate for the recombinant E. coli whole‐cell biocatalysis to efficiently produce the target products (6Z,9Z)‐12‐hydroxydodeca‐6,9‐dienoic acid, (Z)‐9‐hydroxynon‐6‐enoic acid, (Z)‐dec‐4‐enedioic acid, and (6Z,9Z)‐13‐hydroxyoctdeca‐6,9‐dienoic acid [114].

Scheme 2.26 The multiple enzyme biosynthesis of ω‐hydroxyundec‐9‐enoic acid from ricinoleic acid via Baeyer–Villiger oxidation.

Recombinant E. coli expressing CHMO has been extensively used to investigate BV oxidation of cyclohexanone to ε‐caprolactone (Scheme 2.27), which can be influenced by not only the efficient regeneration of NADPH but also a sufficient supply of oxygen [115]. The study of the crystal structure of CHMO reported that two crystal structures are found to bind ε‐caprolactone: the CHMO_Tight and CHMO_Loose structures [116]. The CHMO_Tight structure determines the substrate acceptance and stereospecificity, and the CHMO_Loose is the first structure where the product is solvent accessible. Three regiodivergent BVMOs expressed in E. coli strains have been applied to enantioselectively oxidize a series of cyclic α,β‐unsaturated ketones to produce either chiral enol‐lactones or ene‐lactones, which broadens the scope of BVMO activities [117].

The S‐selective altered CHMO mutant 1‐K2‐F5 (Phe432Ser) from Acinetobacter sp. NCIMB has been tested in the BV oxidative desymmetrization of a number of structurally different ketones with excellent enantioselectivity [118]. An asymmetric BV bio‐oxidation reaction catalyzed by E. coli has been scaled up to a pilot plant (kg) scale using a new “resin‐based in situ substrate feeding and product removal (SFPR)” methodology with nearly enantiopure form (ee > 98%) and good yield [119]. In this application, racemic bicycle[3.2.0]hept‐2‐en‐6‐one was regiodivergent parallel kinetic resolution to two regioisomeric lactones that the (+)‐bicycle[3.2.0]hept‐2‐en‐6‐one enantiomer is converted into the “expected” (−)‐(1S,5R) lactone and (−)‐bicycle[3.2.0]hept‐2‐en‐6‐one is converted into the “unexpected” (−)‐(1R,5S) lactone as indicated by Scheme 2.28. The formation of “expected” lactone means that the oxygen is inserted into the more substituted carbon‐carbon bond of the substrate ketone.

Scheme 2.27 The Baeyer–Villiger oxidation of cyclohexanone to ε‐caprolactone by recombinant E. coli expressing cyclohexanone monooxygenase (CHMO).

Scheme 2.28 Enantiopure asymmetric microbial Baeyer–Villiger oxidation of rac‐bicyclo[3.2.0]hept‐2‐en‐6‐one.