Enzyme-Based Organic Synthesis. Cheanyeh Cheng
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Название: Enzyme-Based Organic Synthesis
Автор: Cheanyeh Cheng
Издательство: John Wiley & Sons Limited
Жанр: Химия
isbn: 9781118995150
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2.1.7 Baeyer–Villiger Reactions
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 CHMOTight and CHMOLoose structures [116]. The CHMOTight structure determines the substrate acceptance and stereospecificity, and the CHMOLoose 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.
2.1.8 Peroxidation Reactions
In mammalian cells, hydrogen peroxide and organic hydroperoxides are synthesized continuously during aerobic metabolism. Peroxides can damage the cell components by their formation of highly reactive hydroxyl radicals that can initiate lipid peroxidation, to oxidize amino acid side chains in proteins, and to cause DNA strand breaks and base modification [120]. Therefore, peroxides must be detoxified continuously to prevent oxidation of cellular components by peroxides or peroxide‐derived reactive oxygen species (ROS). In addition, the generation of peroxides in cells consumes oxygen, which causes the disposal of peroxides particularly important for human brain because brain cells utilize 20% of the oxygen used by the body [121]. In cells, H2O2 is produced by the disproportionation of superoxide generated through the mitochondrial respiratory chain as a by‐product with superoxide dismutases (SODs). Besides, H2O2 can also be produced by the reactions using oxidases such as monoamine oxidases [122]. Stereospecifically defined organic peroxides are generated in cells through the pathways of prostaglandins and leukotrienes by cyclooxygenases and lipoxygenases. Hydroperoxides are also formed by unspecific oxidation of polyunsaturated fatty acids in membranes by radical‐mediated lipid peroxidation [123].
Although not too many enzymatic syntheses of peroxides can be found in literature because of their substrate‐dependent processes, peroxides are of interest to synthetic chemists due to their potent antimalarial and antimicrobial properties [124–126]. Crude enzyme from marine green algae, Ulva pertusa, has been used for the enantioselective α‐hydroxylation of long‐chain saturated and unsaturated fatty acids to corresponding (R)‐2‐hydroperoxy acids (Scheme 2.29) with >99% e.e. enantiopurity. The product of the same hydroperoxylation performed with either brown or red algae on palmitic acid was also (R)‐2‐hydroperoxy acid in >99% e.e. enantiopure.
Scheme 2.29 Enantioselective 2‐hydroperoxylation СКАЧАТЬ