A total conformational analysis of diastereomeric esters and calculation of their conformational shielding models

Tamp, Sven; Danilas, Kady; Kreen, Malle; Vares, Lauri; Kiirend, Ene; Vija, Sirje; Pehk, Tõnis; Parve, Omar; Metsala, Andrus

doi:10.1016/j.theochem.2007.10.045

Cited by 10 publications

(9 citation statements)

References 33 publications

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“…For the current research, -methoxyphenylacetic acid (MPA) 2-butyl esters ( Figure 1) were chosen as subject compounds. They are diastereomeric esters of the well-known chiral derivatizing agent for NMR spectroscopic analysis [8,[19][20][21]. In the current work they are mere model compounds for calculation ( Figure 1).…”

Section: Introductionmentioning

confidence: 97%

“…Having previously followed such guidelines in the total conformational analysis of several esters with up to 11 dihedrals in their structure, the initial optimization of thousands of conformers all together have afforded reliable sets of conformers. The following higher level optimization of the selected conformers has led to the results that, in turn, have allowed calculation of the molecular shielding models in exceptional accordance with differential shielding effects in the NMR spectra [8].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…DFT and the hybrid B3LYP functional have allowed accurate computation of the geometries concerning the type of molecules under study [8]. This, in turn, has allowed calculating NMR and IR spectral characteristics in very good agreement with the experimental data [8,11,12]. The DF method using the B3LYP hybrid functional has been proven to give a good estimate of the electron correlation for some molecules, in particular, in conformational studies, when it is used with the 6-31G * or 6-311++G * * basis set [13,14].…”

Section: Introductionmentioning

confidence: 99%

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An Assessment of Alternative Low Level Calculation Methods for the Initial Selection of Conformers of Diastereomeric Esters

Metsala

Tamp

Danilas

et al. 2014

Journal of Theoretical Chemistry

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Critical assessment of performance of alternative molecular modeling methods depending on a specific object and goal of the investigation is a question of continuous interest. This prompted us to demonstrate the origin of the guidelines we have used for a rational choice and use of a proper low level calculation method (LLM) for an initial geometry optimization of generated conformers, with the aim of selecting a set for further optimization. What was performed herein was a comparison of LLMs: MM3, MM+, UFF, Dreiding, AM1, PM3, and PM6 on the optimization of conformers' geometry of -methoxyphenylacetic acid (MPA) 2-butyl esters as a set of typical diastereomeric esters of a chiral derivatizing agent. This set of esters calculated represents only compounds of this certain type in the current work. The LLM conformer energies were correlated with benchmark energies found by using higher level reference method B3LYP/6-311++G * * on the geometries gained previously by optimization with LLMs. In an alternative treatment, the energy range to be covered and corresponding number of LLM optimized conformers obligatory for submitting to further optimization using a high level optimization cascade were considered on the basis of determination of the cut-off conformer (COFC).

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Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

An Assessment of Alternative Low Level Calculation Methods for the Initial Selection of Conformers of Diastereomeric Esters

Metsala

Tamp

Danilas

et al. 2014

Journal of Theoretical Chemistry

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“…Developing methods in three fields: 1) for linking together chiral compounds, 2) for the analysis of diastereomeric ratio (dr) of the conjugates gained, and 3) for the determination of enantiomeric ratio (er) of chiral starting compounds forms a symbiotic process. For instance, a number of methods based on nuclear magnetic resonance (NMR) [15][16][17][18][19][20][21][22][23][24][25] spectroscopy of diastereomers are used for the determination of er and the absolute configuration of chiral compounds.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Quantitative Analysis of Diastereomeric Linked Ester Conjugates With Remote Stereocenters Using High‐Field NMR and Chiral HPLC

et al. 2013

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A stereochemically safe high-yielding procedure for linking unprotected as well as protected hydroxycarboxylic acids to chiral secondary alcohols via glycolic acid linker is proposed. L-menthol has been linked with both enantiomers of mandelic, malic, and methoxyphenylacetic acid using bromo- or iodoacetyl group as a precursor of the glycolic acid linker. High-field nuclear magnetic resonance (NMR) and chiral high-performance liquid chromatography (HPLC) determination of high diastereomeric ratio (dr) (>99%) of the products bearing remote stereocenters was explored. Chiral HPLC allowed quantitation of the diastereomers up to dr 99.9/0.1. High-field NMR quantitation of the diastereomeric and parent alcoholic impurities in esters was demonstrated at the molar 0.3% and 0.03% levels, respectively. These analyses were done via comparison of integral intensities from major component (13)C satellites in (1)H or even in (13)C spectra to the (1)H or (13C signals of impurities. Despite lower sensitivity, the last option generally has much better selectivity. In this way the dynamic resolution is brought down by two orders.

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Stereoselective Synthesis of γ‐(Acyloxy)carboxylic Acids and γ‐Lactones Featuring the Switch of Stereopreference of Candida antarctica Lipase B in Sodium γ‐Hydroxycarboxylate Homologues

et al. 2022

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Scalable protocols of straightforward synthesis of enantiomeric γ‐(acyloxy)carboxylic acids and γ‐lactones are presented. The key step is lipase‐catalyzed stereoselective acylation of γ‐hydroxycarboxylic acid sodium salt in organic solvent followed by acidification of the product, extraction and acidic relactonization of the unreacted enantiomer. The mixture of γ‐(acyloxy)carboxylic acid and γ‐lactone is separated either by extraction with solution of sodium bicarbonate or by distillation. A switch of enantioinduction of Candida antarctica lipase B along homologous nucleophiles from R configuration of γ‐hydroxyhexanoic acid salt to S configuration of the C7 and longer‐chain homologues has been disclosed. Both enantiomers of γ‐(acyloxy)pentanoic acids; γ‐(acetyloxy)octanoic and ‐nonanoic acids with S configuration; [(1S,5R)‐5‐(chloroacetyloxy)cyclopent‐2‐en‐1‐yl]acetic acid and enantiomeric γ‐lactones derived from them were prepared with e. r. >98.5/1.5. The rates of acylation of C5 to C9 homologous salts differ by three orders of magnitude but remain applicable for preparative synthesis by variation of the enzyme loading and reaction time.

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A total conformational analysis of diastereomeric esters and calculation of their conformational shielding models

Cited by 10 publications

References 33 publications

An Assessment of Alternative Low Level Calculation Methods for the Initial Selection of Conformers of Diastereomeric Esters

An Assessment of Alternative Low Level Calculation Methods for the Initial Selection of Conformers of Diastereomeric Esters

Synthesis and Quantitative Analysis of Diastereomeric Linked Ester Conjugates With Remote Stereocenters Using High‐Field NMR and Chiral HPLC

Stereoselective Synthesis of γ‐(Acyloxy)carboxylic Acids and γ‐Lactones Featuring the Switch of Stereopreference of Candida antarctica Lipase B in Sodium γ‐Hydroxycarboxylate Homologues

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