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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Another method used for the preparation of enantiopure (S)‐1‐phenyl‐1,2‐ethanediol from the racemic (R,S)‐1‐phenyl‐1,2‐ethanediol was performed with the whole‐cell yeast Candida parapsilosis. In this method, (R)‐1‐phenyl‐1,2‐ethanediol is first stereoselectively oxidized to 2‐hydroxyacetophenone by a (R)‐specific ADH, and subsequently the intermediate is stereoselectively reduced by an (S)‐specific carbonyl reductase to form (S)‐1‐phenyl‐1,2‐ethanediol (Scheme 2.4). The catalytic activities of the two key enzymes in C. parapsilosis responsible for the deracemization were significantly enhanced by the increase of dissolved oxygen concentration with higher agitation speed [12].
Scheme 2.3 Regio‐ and stereoselective concurrent oxidations of (±)‐1,2 diols.
Scheme 2.4 Deracemization of racemic 1‐phenyl‐1,2‐ethanediol by C. parapsilosis through an oxidation–reduction sequence.
Enantiopure sec‐alcohols and α‐hydroxyketones (acyloins) are popular and important synthons for the asymmetric synthesis of many bioactive compounds [13–15]. A biocatalytic racemization is proved to be a useful tool for the preparation of enantiopure simple alcohols and acyloins via an enzymatic oxidation–reduction process with the formation of a nonchiral ketone or α‐diketone intermediate, respectively, using whole lyophilized cells of various bacteria, fungi, and one yeast [16]. The kinetic resolution process was applied for three selected sec‐alcohols (2‐octanol, 6‐methyl‐5‐heptene‐2‐ol, and 1‐phenylethanol) and three selected acyloins (benzoin, phenyl acetylcarbinol, and 2‐hydroxy‐1‐indanone) in which phenyl acetylcarbinol and derivatives are key intermediates for industrially manufacturing (−)‐(pseudo)ephedrine, antidepressants, and smoking cessation agents [17–20], and 2‐hydroxy‐1‐indanone is used for the synthesis of several human immunodeficiency virus (HIV)‐protease inhibitors [21, 22]. Sec‐alcohol dehydrogenases and α‐diketone reductases are responsible for the equilibrium‐controlled enzymatic oxidation–reduction sequence, respectively, and the racemization protocol gives (S)‐enantiomers (Scheme 2.5).
Glucose dehydrogenases, glucose oxidases, and gluconate dehydrogenases have been exploited for the oxidation of aldoses on large‐scale applications and biosensors [1]. For instance, glucose oxidase (GOx) has been widely employed in enzymatic kits for fast glucose determination and for the industrial production of gluconic acid from glucose, which was carried out using whole cells of Aspergillus niger. The industrial production of gluconic acid from glucose can be also performed by a membrane‐bound dehydrogenase from G. oxydans. A more recent industrial application of GOx is the direct oxidation of D‐glucosamine to D‐glucosaminic acid with the combined use of catalase to degrade the H2O2 produce.
Scheme 2.5 Biocatalytic racemization of sec‐alcohols and acyloins using lyophilized microbial cells.
Direct oxidation of heterocyclic and aromatic aldehydes to the corresponding carboxylic acids can be accomplished by Acetobacter rancens IFO3297, Acetobacter pasteurianus IFO13753, and Serratia liquefaciens LF14 [1, 23]. For instance, oxidation of furfural by A. rancens IFO3297 can produce 110 g L−1 of 2‐furoic acid with a 95% yield. 5‐Hydroxymethyl‐2‐furancarboxylic acid obtained from corresponding aldehyde can be obtained by whole cells LF14. Isophthalaldehyde, 2,5‐furandicarbaldehyde, 2,5‐thiophenedicarbaldehyde, and 2,2′‐biphenyldicarbaldehyde can be converted to the corresponding formylcarboxylic acid with 86–91% yields by both IFO13753 and LF14. The aromatic carboxylic acids such as vanillic acid, p‐hydroxybenzoic acid, and syringic acid can be produced by the oxidation of corresponding aromatic aldehydes using whole‐cell Burkholderia cepacia TM1 [1, 24].
The oxidation of alcohols and aldehydes to form corresponding aldehydes, ketones, and carboxylic acids has also been used by cells to produce important intermediates or precursors during the biosynthetic pathways. In the biosynthesis of depside atranorin from acetate using immobilized lichen cells Evernia prunastri, the most probable precursor, an aldehyde‐substituted phenolic aldehyde, haematommic acid, is produced by oxidation of an alcohol intermediate as shown in Scheme 2.6 [25]. In another example, resting cells of Nocardia iowensis DSM 45197 have been selected for the synthesis of vanillin and vanillic acid from the starting material isoeugenol. Three possible pathways used by N. iowensis have been suggested for the conversion of isoeugenol to vanillic acid and vanillin. 18O‐labeling studies showed that most likely route appears to be the initial side‐chain olefin epoxidation of isoeugenol, epoxide hydrolysis to a vicinal diol, followed by diol cleavage to vanillin and subsequently oxidation of the aldehyde group of vanillin to vanillic acid by an aldehyde oxidase (Scheme 2.7) [26].
Scheme 2.6 Oxidation of an alcohol intermediate to the precursor of atranorin in the biosynthetic pathway of lichen cells.
Scheme 2.7 Bioconversion of isoeugenol to vanillin and vanillic acid by N. iowensis.
2.1.2 Hydroxylation of Alkanes
Alkanes are saturated hydrocarbons that constitute about 20–50% of crude oil, and living organisms, such as bacteria, plants, and some animals, also produce them. They are chemically quite inert, low value, and usually burned as energy source to produce carbon oxides. Thus, there are two main reasons to carry out the catalytic hydroxylation of inert C–H bonds in alkanes for chemical industry applications. The first one is the providing of high‐value compounds from the low‐value oil refinery products such as the manufacturing of solvents, plasticizers, and surfactants. The second one is the removal of pollutants from the environment [27, 28].
Because carbon and hydrogen atoms have almost equal electronegativity, the activation of alkanes by the hydroxylation process, especially at the terminal positions, remains a challenging topic in synthetic chemistry. СКАЧАТЬ