Enol reductase

Enolate anion, reaction, 10 505 Enolate initiators, 14 258 Enolate reductases, 3 674 Enolboration, 13 671-672 Enol properties, of 1,3-diketones,... 

Enolate reductase Reduction of enones, a,p-unsaturated esters Whole-cell systems Isolated enzymes... 

KR), dehydratase (DH), and enol reductase (ER) domains while docked at the ACP. Once fully processed, the extended chain is passed to the KS of the subsequent module by a transthioesterification reaction. The process is repeated, leading to the final module where the product is generally excised via hydrolysis or thioesterase (TE) mediated macrocyclization. 

Scheme 13. Proposed mode of action of ery-thromycin-PKS. KS = ketoacyl synthase KR = keto reductase DH = deydratase ER = enol reductase ACP = acyl carrier protein CoA=coenzyme A.

Reaction of phthalic anhydride (70-1) with the ylide from ethyl triphenylphos-phoniumacetate leads to the condensation product (70-2), which in effect consists of a cyclic enol anhydride. Treatment of this product with hydrazine leads to the hydrazone-hydrazide (70-3). Alkylation of the anion from removal of the hydrazide proton with the substituted benzyl bromide (70-4) affords the alkylation product (70-5). Saponification then leads to the aldose reductase inhibitor ponalrestat (70-6) [79]. 

Lack of congruence of structure and mechanism Common structure does not imply a common mechanism The /1-barrel structures triosephosphate isomerase and xylose isomerase function by hydride transfer through enol, whereas aldose reductase performs hydride transfer through a metal ion. 

Enol radical cation intermediates have rerantly been invoked in the ribonucleotide reductase process. According to a hypothesis by Stubbe [127], they are formed through water loss from the 3 -ribonucleotide radical. They are supposed to react subsequently with H (or alternatively via a very unlikely two-electron reduction followed by protonation) to an intermediate 3 -hydroxy radical that is finally transformed to the deoxyribonucleotide. The above mechanistic evidence on simple enol radical cation chemistry, however, argues against this mechanistic model, since deprotonation should be much faster than nucleophilic attack even under physiological conditions. 

Fujita, A., Soma, N., Goto-Yamamoto, N., Shindo, H., Kakuta, T., Koizumi, T. and Hashizume, K. (2005) Anthocyanidin reductase gene expression and accumulation of flavan-3-ols in grape berry, Am. J. Enol. Vitic., 56(4), 336-342. 

The keto-sugar nucleotide dTDP-L-rhamnose is synthesized from dTDP-4-keto-6-deoxy-D-glucose by dTDP-i-rhamnose synthase [104, 105). The enzyme consists of two components, a cofactor independent epimerase and an NADH-dependent reductase. The epimerase component is inactive without the reductase component. The mechanism involves epimerization of two stereocenters flanking a carbonyl group, via sequential deprotonation/reprotonation, with two enol intermediates. Complete solvent isotope incorporation into both epimerized stereocenters was observed, and primary substrate-derived KIEs have been determined [104],... 

Lee, H., Reyes, V. M., Kraut, J. (1996) Crystal structures of Escherichia coli dihydrofolate reductase complexed with 5-formyltetrahydrofolate (folinic acid), in two space groups evidence For enolization of pteridine 04, Biochemistry 35, 7012-7020. 

AcetoacetylCoA thiolase (E.C. 2.3.1.9), acetoacetylCoA reductase (E.C. 1.1.1.36), and polyhydroxybutyrate synthetase12471 are the enzymes involved in polyester synthesis. AcetoacetylCoA thiolase catalyzes the head-to-tail Claisen condensation of two acetylCoA molecules. In this reaction, the active site cysteine attacks acetylCoA to form a thioester enzyme intermediate, which then reacts with the enolate derived from enzymatic deprotonation of the other acetylCoA. Mechanistic studies have been performed on this enzyme from Zooglea ramigera, which has been cloned and overexpressed12471. It has been established that the thiolase will form acyl enzyme intermediates with a number of acylCoA substrates, but will only accept acetylCoA as the nucleophile. After subsequent reduction, this results in all polymer units possessing a P-hydroxy group. These polymers are also useful sources of (R)-P-hydroxy acids[2481. 

The major rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl Coenzyme A reductase (HMG-CoA reductase), has been a therapeutic target for many research groups. A synthesis of the functionalized thiophene 172, prepared for its biological activity, illustrates the utility of 162 for the introduction of one of the hydroxy chiral centers present in the molecule. This chiral center is then exploited for the introduction of the second chiral hydroxy center. Treatment of aldehyde 169 with the double anion of 162 at —95 °C in THF affords as the major product 170 (98.8 1.2). Treatment of the adduct with excess tert-butylacetate enolate at — 78 °C followed by acidic work-up furnishes the jS-hydroxyketone 171 in 86% isolated yield. Chelation-controlled reduction of the ketone, accomplished by initial complexation of the ketone and the hydroxy group with triethylborane followed by sodium borohydride addition, provides the desired dihydroxyester 172 (Scheme 39) [47]. 

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