Enhancement and Reversal of Enantioselectivity of the Enzymatic Hydrolysis of (RS)-3-(4-Methoxycarbonyl)phenyl-2-methylprop-1-yl Acetate upon its Transformation into the η6-Arene(tricarbonyl)chromium Complex

Serebryakov, É. P.; Gamalevich, G. D.; Strakhov, A. V.; Васильев, А. А.

doi:10.1070/mc1995v005n05abeh000509

Cited by 8 publications

(7 citation statements)

References 5 publications

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“…Zemplen saponification of acetate (S)-IIIa gave alcohol (S)-III in 98% yield. PMR spectra of the obtained compounds agreed fully with those of (R)-III and (S)-III that were isolated earlier[8]. The correlation of the [a] D values found earlier for products with 100% ee and for the synthesized (R)-III and (S)-III indicated that their enantiomeric purities were 89.5 and 96%, respectively.…”

supporting

confidence: 72%

“…The addition of them could have a favorable effect on the enzyme microenvironment [6,7]. Amines, crown ethers, moistened sodium or lithium salts, and various combinations of enzymes with added Group IV -VII elements (Si, Cr, Ru) were used as such additives.We settled on a previously unused approach, i.e., a drastic change of the electronic and steric properties of the substrate by converting it into the corresponding racemic arene(tricarbonyl)chromium complex of alcohol (RS)-IV [5] and/or its acetate (RS)-IVa [8]. …”

mentioning

confidence: 99%

“…We settled on a previously unused approach, i.e., a drastic change of the electronic and steric properties of the substrate by converting it into the corresponding racemic arene(tricarbonyl)chromium complex of alcohol (RS)-IV [5] and/or its acetate (RS)-IVa [8].…”

mentioning

confidence: 99%

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Synthesis of the Racemate and Both Enantiomers of Biologically Active 4-(2,6-Dimethylheptyl)Benzoic Acid and Their Effect on Cholesterol Accumulation in Aorta Cells

2015

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A chemical and enzymatic approach to the synthesis of (S)-and (R)-3-(4-methoxycarbonyl)phenyl-2-methyl-1-propanols, convenient intermediates for the synthesis of both enantiomers of 4-(2,6-dimethylheptyl)benzoic acid, was described. The biological activity of (R)-and (S)-isomers of the racemic acid was studied. It was established that the (S)-configuration of its antipode in the racemate decreased the cholesterol level in aorta cells.Keywords: (R)-and (S)-4-(2,6-dimethylheptyl)benzoic acids, (S)-and (R)-3-(4-methoxycarbonyl)phenyl-2-methyl-1-propanols and their h 6 -chromiumtricarbonyl complexes, porcine pancreatic lipase (PPL), aorta cholesterol level.Racemic 4-(2,6-dimethylheptyl)benzoic acid [(RS)-I] reduces effectively the in vivo blood level of excessive cholesterol [1] and also suppresses cholesterol accumulation in human atherosclerotic aorta cells in culture [2] more strongly that standard Clofibrate ® . This makes it promising in the battle with atherosclerosis. However, the pharmacological properties of the pure enantiomers (R)-I and (S)-I have not been previously studied because the acids themselves were unknown.We developed previously [3] a stereo-divergent synthetic scheme in order to synthesize the undescribed acids (R)-I and (S)-I from the common precursor enal II [4] through racemic alcohol (RS)-III. The scheme included enzymatic kinetic separation of (RS)-III using porcine pancreatic lipase (PPL).The PPL-catalyzed kinetic separation of the (RS)-acetate of 3-(4-methoxycarbonyl)phenyl-2-methyl-1-propanol produced the (R)-III and (S)-III enantiomers of the corresponding alcohol with 22 -27% optical purity. The enantiomeric excess (ee) could not be increased above 33% with repeated enzymatic hydrolysis of the "residual" acetate under the same conditions. Partial acylation [5] of (RS)-III alcohol using vinylacetate-Candida cylindracea (CCL) also did not give products with the required high enantiomeric purity.The limited choice of lipases with high enantiomeric selectivity for racemic substrate (RS)-III and the desire to synthesize pure enantiomers of (R)-III and (S)-III with an acceptable ee for synthesizing target acids (R)-I and (S)-I prompted us to seek new approaches for solving this problem.Examples where the selectivity of lipases was increased by adding chemical additives to the reaction mixture were reported. The addition of them could have a favorable effect on the enzyme microenvironment [6,7]. Amines, crown ethers, moistened sodium or lithium salts, and various combinations of enzymes with added Group IV -VII elements (Si, Cr, Ru) were used as such additives.We settled on a previously unused approach, i.e., a drastic change of the electronic and steric properties of the substrate by converting it into the corresponding racemic arene(tricarbonyl)chromium complex of alcohol (RS)-IV [5] and/or its acetate (RS)-IVa [8].

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confidence: 72%

mentioning

confidence: 99%

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Synthesis of the Racemate and Both Enantiomers of Biologically Active 4-(2,6-Dimethylheptyl)Benzoic Acid and Their Effect on Cholesterol Accumulation in Aorta Cells

2015

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“…First, the acetate fraction was collected (yield 34%), while further elutiot~ with pure Et20 afforded a specimen of alcohol (R)-6 with laiD 20 +14.40 ~ (c 0.95, CHCI3); yield 120 mg (96~~ This alcohol (86 rag, 0,25 retool) was dissolved in THF (5i mL) and oxidized with a saturated solution of 12 in THF (2.5 mL). After 24 h of exposure at 20--22 ~ followed by the standard work-u~, it was transformed into alcohol (R)-$ with ~CtlD20 + 10.42 ~ (c 0.58, CHCI~): yield 485 g (92%L The ,values of ICtlD found for these specimens of (R)-6 and (R)-5 correspond to about 100% enantiomeric purity of both alcohols, (cf Refs 11,12). …”

Section: H 2-h)mentioning

confidence: 99%

Enantioselectivity of enzymatic acylation of some structurally various racemic alcohols in anhydrous aprotic media

Gamalevich

Serebryakov

1997

Russ Chem Bull

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Partial acylation of (R,S)-3,7-dimethyloctan-1 -ol (1) and (R,S)-7-methoxy-3,7-dimethyloctan-l-ol (2) with vinyl acetate catalyzed by the lipase from Candida cylindracea affords in good yields the corresponding S-configured acetates with 92--98% enantiomeric excess (ee). Under similar conditions, racemic ct-cyelogeraniol (3), drim-7-en-ll-ol, methyl 4-(3-hydroxy-2-methylpropyl)benzoate, and its rl6-chromium(tricarbonyl) complex (6) are acylated with rather poor (and, for the two latter, opposite) enantioselectivity, whereas (R,S)-2,4:3,5-di-O-benzylidenexylitol remains unaffected. Raeemic isoborneol (8) and 2-nitro-l-phenylethanol also remain almost or completely unconverted. Attempts to perform enantioselective acylation of alcohols 3 and $ with Ac20 in the presence of porcine pancreatic lipase (PPL) proved equally unsuccessful. By contrast, the PPL-catalyzed acylation of alcohol 6 with vinyl acetate at 17% conversion affords the levorotatory acetate (S)-61 with ca. 100% ee. PPL-Mediated partial acylation of (R,S)-pantolactone with Ac20 , followed by mild deacylation of the resulting R acetate, gives (R)-(-)-pantolactone of 97% enantiomeric purity in 60% overall yield.

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“…Ìû ïðèáåãëè ê ðàíåå íå èñïîëüçîâàâøåìóñÿ ïðèåìó -ðåçêîìó èçìåíåíèþ ýëåêòðîííûõ è ñòåðè÷åñêèõ õàðàêòåðèñòèê ñóáñòðàòà ïóòåì åãî ïðåâðàùåíèÿ â ñîîòâåòñòâóþùèé ðàöåìè÷åñêèé àðåí(òðèêàðáîíèë)õðîìîâûé êîìïëåêñ ñïèðòà (RS)-IV [5] è/èëè åãî àöåòàòà (RS)-IVà [8].…”

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Синтез Рацемата И Обоих Энантиомеров 4-(2,6-Диметилгептил)бензойной Кислоты И Их Влияние На Накопление Холестерина В Клетках Аорты

Gamalevich¹,

Власюк²,

Серебряков³

2015

Хим.-фарм. ж.

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Разработан химико-ферментативный подход к синтезу (S)- и (R)-3-(4-метоксикарбонил)фенил-2-метил-1-пропанолов, удобных интермедиатов для получения обоих энантиомеров 4-(2,6-диметилгептил)бензойной кислоты. Исследована биологическая активность (R)- и (S)-компонентов рацемической кислоты. Установлено что (S)-конфигурация ее антипода в рацемате снижает уровень холестерина в клетках аорты.

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Enhancement and Reversal of Enantioselectivity of the Enzymatic Hydrolysis of (RS)-3-(4-Methoxycarbonyl)phenyl-2-methylprop-1-yl Acetate upon its Transformation into the η6-Arene(tricarbonyl)chromium Complex

Cited by 8 publications

References 5 publications

Synthesis of the Racemate and Both Enantiomers of Biologically Active 4-(2,6-Dimethylheptyl)Benzoic Acid and Their Effect on Cholesterol Accumulation in Aorta Cells

Synthesis of the Racemate and Both Enantiomers of Biologically Active 4-(2,6-Dimethylheptyl)Benzoic Acid and Their Effect on Cholesterol Accumulation in Aorta Cells

Enantioselectivity of enzymatic acylation of some structurally various racemic alcohols in anhydrous aprotic media

Синтез Рацемата И Обоих Энантиомеров 4-(2,6-Диметилгептил)бензойной Кислоты И Их Влияние На Накопление Холестерина В Клетках Аорты

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