Enzyme-Based Organic Synthesis. Cheanyeh Cheng

Enzyme-Based Organic Synthesis - Cheanyeh Cheng


Скачать книгу
bind carbonic anhydrase with only one point through the cofactor zinc ion and react to form bicarbonate or the reversible reaction [10]. Another example for small molecule is the binding of a covalent adduct formed between pyruvate and nicotinamide adenine dinucleotide (NAD+) to lactate dehydrogenase (LDH) to produce lactate in which only two binding points, namely, the carbonyl group and the carboxylate group, of pyruvate are used to bind with the LDH [12]. The number of binding sites of an enzyme to the substrate is important in determining the type of enzyme specificity. The molecular recognition for enzyme specificity has been categorized into three major types of specificities: substrate specificity, regiospecificity, and stereospecificity [13].

      1.4.1 Substrate Specificity

      1.4.2 Regiospecificity

      Some of the enzymes may selectively catalyze one functional group at certain region of the molecule among several similar functional groups located at different regions of the same molecule. This kind of substrate specificity is called regiospecificity or diastereospecificity [13]. Example of regiospecificity in organic synthesis has been found since 1986 that the regioselective deacylation of methyl 2,3,4,6‐tetra‐O‐acyl‐D‐hexopyranosides gives the 6‐OH derivatives in high yields using the lipase from Candida cylindracea [14]. The enzyme‐catalyzed regioselective O‐acylation of ribo‐, arabino‐, xylo‐, rhamnopyranosides, and aryl pyranosides is reviewed, and the methodology is applied to the total synthesis of the naturally occurring rhamnopyranoside by Bashir et al [15]. Regioselective biotransformation of dinitrile compounds 2‐, 3‐, and 4‐(cyanomethyl) benzonitrile can be performed by whole bacterium cell Rhodococcus rhodochrous to the corresponding 2‐(cyanophenyl) acetic acid, 3‐ or 4‐(cyanomethyl) benzoic acid with high yield [16]. Whole cell bacterium Bacillus cereus has also been used for regioselectively converting 2‐phenylenediamine to 2‐aminoacetanilide with a76% molar yield [17]. Other than bacterium, monooxygenase in the phytopathogenic fungi Colletotrichum gloeosporioides and Botrytis cinerea has been found having the ability of regioselective hydroxylation of the C‐H bonds to yield the corresponding diols [18]. Enzyme in cultured plant cells of Phytolacca Americana can reduce, and regioselectively hydroxylate and glucosylate, raspberry ketone and zingerone to their β‐glycosides [19]. Ginkgo biloba cell suspension cultures were used to regio‐ and stereoselectively convert sinenxan A, 2α,5α,10β,14β‐tetra‐acetoxy‐4(20), 11‐taxadiene, a taxoid isolated from callus tissue cultures of Taxus spp., in Taxol® synthesis [20]. The regioselective oxidation of (–)‐verbenone, an important component of the essential oil from rosemary, to (–)‐10‐hydroxyberbenone with human liver microsomes has been investigated by Miyazawa et al [21]. Although regioselective oxidation of terpenoids is difficult by chemical methods, regioselective oxidation of (+)‐ and (–)‐citronellene was recently performed with Spodoptera litura, a larvae of common cutworm, to (2R,3S)‐3,7‐dimethyl‐6‐octene‐1,2‐diol (yield: 89.7%) and (2S,3R)‐3,7‐dimethyl‐6‐octene‐1,2‐diol (yield: 56.3%) [22]. These examples of enzyme‐catalyzed regiospecificity clearly elucidates that the specific enzyme–substrate binding configuration at the active site allows only one of several similar function groups in different regions of the substrate molecule reacts to produce the product. The number of binding points of enzyme–substrate complex for regioselective molecular recognition must be a “multi‐point” binding case to match the complexity of the substrate molecule.

      1.4.3 Stereospecificity

      The most magnificent specificity of enzyme is its distinguishable ability for only one enantiomeric structure of racemic substrate molecules. The molecular recognition of an enzyme for enantiomeric molecules is called enantiospecificity or stereospecificity. The stereospecificity is an intrinsic property of enzyme which is due to the chirality of active site of the enzyme. Except for a few cases, all enzymes are chiral catalysts because they all made from L‐amino acids, thus the binding of asymmetric substrate at the active site is stereoselective. Since the stereospecificity of enzyme involves enzyme–substrate complex formation with only one enantiomer of a racemate, only one product is formed from the enzyme‐catalyzed reaction. Therefore, enzyme‐catalyzed reactions are in great favor of the organic asymmetric synthesis [23].


Скачать книгу