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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The one‐pot epoxidation of cyclohexene and N‐benzyloxycarbonyl‐3,4‐dihydroxy‐pyrrolidine by Novozym 435® gave cyclohexene oxide and (3R,4R)‐N‐benzyloxycarbonyl‐3,4‐epoxy‐pyrrolidine, respectively, which were subsequently trans‐dihydrolyzed by resting cells of Sphingomonas sp. to produce corresponding trans‐vicinal diols in high enantiomeric excess values and high yields [88]. The silicone composites of Novozym 435 (silicoat‐NZ435) have been used in the solvent‐free three‐phase system chemoenzymatic epoxidation of 1‐dodecene to demonstrate the ability of the most difficult terminal alkene epoxidation [89]. The reaction showed an 80% yield with almost 100% selectivity and is better than the native Novozym 435 (NZ435).
Growing cells and resting cells of recombinant E. coli containing the styrene monooxygenase StyAB were used for enantioselective styrene epoxidation to efficiently produce (S)‐styrene oxide in an organic/aqueous two‐liquid‐phase system and batch or fed‐batch reaction [90–93]. Styrene monooxygenase (StyAB) from Pseudomonas sp. VLB120 is composed of an FAD‐dependent monooxygenase component (StyA) that catalyzes the epoxidation reaction and an NADH‐dependent reductase component (StyB) that delivers the reducing equivalents from NADH to StyA via FADH2 [94]. The enzyme StyAB catalyzes the specific (S)‐epoxidation of a broad range of m‐ and p‐ as well as α‐ and β‐substituted styrene derivatives [95]. Since the motif of enantiopure 1,2‐amino alcohol is present in alkaloids, amino sugars, enzyme inhibitors, and antibiotics, various enantiopure 2‐phenyl, 2‐amino ethanols were prepared chemically through the nitrogen nucleophilic addition to the epoxy group of a number of styrene epoxide derivatives (Scheme 2.22) [96]. However, the formation of various styrene epoxide derivatives was performed enzymatically by using the recombinant E. coli to oxidize various styrene derivatives. The bioconversions were performed in an aqueous buffer using an organic phase to separate both the epoxide product and unreacted styrene derivatives. The enantiomeric excess values for epoxide products are quite high (>95% e.e.) except the epoxide derived from 1‐phenyl, 2‐methyl propene.
Two reasons cause monooxygenase catalyzed epoxidation reactions using whole cells rather than isolated enzyme more attractive, which are the very unstable monooxygenase in vitro and the easy regeneration of the cofactor for NAD(P)H‐dependent monooxygenase in whole cell. The epoxidation of ally phenyl ether (APE) for producing chiral phenyl glycidyl ether (PGE) with an enantiomeric excess of 86% has been investigated by encapsulating whole‐cell Mycobacterium M156 in water‐in‐oil reverse micelles [97] as in Scheme 2.23.
Scheme 2.22 The synthesis of enantiopure 2‐amino‐1‐phenyl and 2‐amino‐2‐phenyl ethanols through enantioselective enzymatic epoxidation of styrene derivatives.
Scheme 2.23 Epoxidation of ally phenyl ether for producing chiral phenyl glycidyl ether.
Scheme 2.24 Stereoselective epoxidation of unsaturated bicyclic γ‐lactones.
The epoxidation of cis‐propenylphosphonic acid (cPPA) by bacterium Bacillus simplex strain S101 has been used for the preparation of fosfomycin that is more delicate, environmentally friendly, and has a higher conversion yield (81.3%) than the large‐scale industrial process (<20%) [98]. The biologically active unsaturated bicyclic γ‐lactones (4,4,6‐trimethyl‐9‐oxabicyclo[4.3.0]non‐2‐en‐8‐one (1a) and 4,4‐dimethyl‐9‐oxabicyclo‐[4.3.0]non‐2‐en‐8‐one (1b)) were stereoselectively transformed into the corresponding trans‐epoxylactones (2,3‐epoxy‐4,4,6‐trimethyl‐9‐oxabicyclo[4.3.0]nonan‐8‐one (2a) and 2,3‐epoxy‐4,6‐dimethyl‐9‐oxabicyclo[4.3.0]nonan‐8‐one (2b)) by the strain Absidia cylindrospora as shown in Scheme 2.24 [99]. These epoxylactones can be further converted to yield hydroxylactones with the secondary hydroxy group. Oleic acid in the lipophilic extractives can be oxidized with Pycnoporus cinnabarinus laccase in the presence of 1‐hydroxybenzotriazole (HBT) to form an epoxy oleic acid at the C9 and C10 double bond. The conversion was 88% after a two‐hour treatment [100].
2.1.6 Sulfoxidation Reactions
There are natural organosulfur compounds such as sulfur containing amino acids (cysteine, methionine, and cystine), allicin, lipoic acid, and unnatural organosulfur compounds such as dibenzothiophene in petroleum products or penicillin in pharmaceutical products. Among the variety of organosulfur compounds, chiral organic sulfoxides (COSs) are useful chiral building blocks or stereodirecting groups in asymmetric synthesis of important pharmaceuticals that contain a functional sulfinyl group attached to the alkyl moieties [101, 102]. However, the preparation of COSs also can be obtained through sulfoxidation by the high regioselectivity and stereoselectivity of enzymes [103]. For example, the purified catalase‐peroxidase (KatG) characterized as a heme‐containing protein from the bacterium Bacillus pumillis was employed for stereoselective oxidation of β‐lactams, represented by penicillin‐G, penicillin‐V, and cephalosporin‐G to their R‐sulfoxides [104].
The use of co‐expression system that is the co‐expression of formate dehydrogenase from gene originated from Candida boidinii and the cyclohexanone monooxygenase (CHMO) gene cloned from Acinetobacter calcoaceticus NCIMB 9871 in E. coli BL21 has been used as the whole‐cell biocatalyst to selectively synthesize chiral R‐phenyl methyl sulfoxide (R‐PMSO) from thioanisole. In this reaction system, NADPH has also been regenerated to improve the catalytic efficiency [105]. Another strategy was utilized to selectively synthesize corresponding S‐sulfoxide from p‐chlorothioanisole as shown by Scheme 2.25 [106]. In this investigation, the asymmetric oxygenation of sulfide to S‐sulfoxide was with co‐expressed E. coli that contains the P450SMO gene from Rhodococcus sp. and the glucose dehydrogenase gene from Bacillus subtilis. In this study, NADPH was efficiently regenerated when glucose was supplied to the reaction.