Journal articles: 'D-enantiomer'

1

Zhou, Juan, Qiao Chen, Li-lan Wang, Yong-hua Wang, and Ying-zi Fu. "Chiral Discrimination of Tryptophan Enantiomers via (1R, 2R)-2-Amino-1, 2-Diphenyl Ethanol Modified Interface." International Journal of Electrochemistry 2011 (2011): 1–6. http://dx.doi.org/10.4061/2011/502364.

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The paper reported that a simple chiral selective interface constructed by (1R, 2R)-2-amino-1, 2-diphenyl ethanol had been developed to discriminate tryptophan enantiomers. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were used for the characteristic analysis of the electrode. The results indicated that the interface showed stable and sensitive property to determine the tryptophan enantiomers. Moreover, it exhibited the better stereoselectivity for L-tryptophan than that for D-tryptophan. The discrimination characteristics of the chiral selective interface for discriminating tryptophan enantiomers, including the response time, the effect of tryptophan enantiomers concentration, and the stability, were investigated in detail. In addition, the chiral selective interface was used to determine the enantiomeric composition of L- and D-tryptophan enantiomer mixtures by measuring the relative change of the peak current as well as in pure enantiomeric solutions. These results suggested that the chiral selective interface has the potential for enantiomeric discrimination of tryptophan enantiomers.

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2

Bystrická, Zuzana, and Jozef Lehotay. "In Vitro Investigation of D- and Lenantiomer Synergistic Efects of Some Amino Acids." Nova Biotechnologica et Chimica 15, no. 1 (June 1, 2016): 47–54. http://dx.doi.org/10.1515/nbec-2016-0005.

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Abstract D-amino acids can arise from endogenous microbial flora, from ingestion with the diet or from spontaneous racemization of L-amino acids during ageing. In this work, the behavior of methionine, homocysteine and cysteine enantiomers was investigated in human serum in vitro during 0-72 h at incubation temperature 37°C. The separation of enantiomers was realized in two dimensional on-line system (the connection of an achiral column Purospher RP-18 endcapped and a chiral column Chirobiotic TAG). This system allowed simultaneous monitoring all tested amino acids and their enantiomers. The possible effect D-enantiomer on the behavior of its L-enantiomer (the synergistic effect) was evaluated during incubation time. The first results have showed that no synergistic effect of D-enantiomer on its Lisomer has been observed in our experimental conditions in vitro.

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Ge, Huilin, Min Zhou, Daizhu Lv, Mingyue Wang, Cunzhu Dong, Yao Wan, Zhenshan Zhang, and Suru Wang. "New Insight Regarding the Relationship Between Enantioselective Toxicity Difference and Enantiomeric Toxicity Interaction from Chiral Ionic Liquids." International Journal of Molecular Sciences 20, no. 24 (December 6, 2019): 6163. http://dx.doi.org/10.3390/ijms20246163.

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Chirality is an important property of molecules. The study of biological activity and toxicity of chiral molecules has important theoretical and practical significance for toxicology, pharmacology, and environmental science. The toxicological significance of chiral ionic liquids (ILs) has not been well revealed. In the present study, the enantiomeric joint toxicities of four pairs of chiral ILs 1-alkyl-3-methylimidazolium lactate to Allivibrio fischeri were systematically investigated by using a comprehensive approach including the co-toxicity coefficient (CTC) integrated with confidence interval (CI) method (CTCICI), concentration-response curve (CRC), and isobole analysis. The direct equipartition ray (EquRay) design was used to design five binary mixtures of enantiomers according to molar ratios of 1:5, 2:4, 3:3, 4:2, and 5:1. The toxicities of chiral ILs and their mixtures were determined using the microplate toxicity analysis (MTA) method. Concentration addition (CA) and independent action (IA) were used as the additive reference models to construct the predicted CRC and isobole of mixtures. On the whole, there was an enantioselective toxicity difference between [BMIM]D-Lac and [BMIM]L-Lac, and [HMIM]D-Lac and [HMIM]L-Lac, while no enantioselective toxicity difference was observed for [EMIM]D-Lac and [EMIM]L-Lac, and [OMIM]D-Lac and [OMIM]L-Lac. Thereinto, the enantiomer mixtures of [BMIM]D-Lac and [BMIM]L-Lac, and [HMIM]D-Lac and [HMIM]L-Lac presented antagonistic action, and the enantiomer mixtures of [EMIM]D-Lac and [EMIM]L-Lac, and [OMIM]D-Lac and [OMIM]L-Lac overall presented additive action. Moreover, the greatest antagonistic toxicity interaction occurred at the equimolar ratio of enantiomers. Based on these results, we proposed two hypotheses, (1) chiral molecules with enantioselective toxicity difference tended to produce toxicity interactions, (2) the highest or lowest toxicity was usually at the equimolar ratio and its adjacent ratio for the enantiomer mixture. These hypotheses will need to be further validated by other enantiomer mixtures.

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Šaman, David, Martina Wimmerová, and Zdeněk Wimmer. "Synthesis and Structure Assignment of 2-(4-Methoxybenzyl)cyclohexyl β-D-Galactopyranoside Stereoisomers." Collection of Czechoslovak Chemical Communications 71, no. 8 (2006): 1186–98. http://dx.doi.org/10.1135/cccc20061186.

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Several promoters were used in the Koenigs-Knorr synthesis of the title alkyl β-D-galactopyranosides, both in their diastereoisomeric forms (5a/5b and 6a/6b), resulting from the synthesis performed with the respective racemic cis and trans isomers of 2-(4-methoxybenzyl)cyclohexan-1-ol, and in their enantiomerically pure forms 5a and 6a, starting only from the (1S,2S)- and (1S,2R)-enantiomers of 2-(4-methoxybenzyl)cyclohexan-1-ol. The aim of the study was to find convenient modification(s) of the Koenigs-Knorr synthesis of alkyl β-D-galactopyranosides from more hindered and more complex 2-substituted cycloalkanols. Separation of the diastereoisomeric compounds using HPLC on a chiral Nucleodex-β-OH column was used to obtain small quantities of all possibly existing enantiomerically pure products for unambiguous structure assignment by NMR analysis. The (1S,2S)- and (1S,2R)- enantiomers of 2-(4-methoxybenzyl)cyclohexan-1-ol (1a and 2a) were prepared by a reduction of 2-(4-methoxybenzyl)cyclohexan-1-one with Saccharomyces cerevisiae in enantiomeric purities: ee = 98.5% ((1S,2S)-enantiomer (1a)), and ee ≥ 99% ((1S,2R)-enantiomer (2a)).

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5

Gao, Jingyao, Haoyang Zhang, Chen Ye, Qilong Yuan, Kuan Chee, Weitao Su, Aimin Yu, et al. "Electrochemical Enantiomer Recognition Based on sp3-to-sp2 Converted Regenerative Graphene/Diamond Electrode." Nanomaterials 8, no. 12 (December 14, 2018): 1050. http://dx.doi.org/10.3390/nano8121050.

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It is of great significance to distinguish enantiomers due to their different, even completely opposite biological, physiological and pharmacological activities compared to those with different stereochemistry. A sp3-to-sp2 converted highly stable and regenerative graphene/diamond electrode (G/D) was proposed as an enantiomer recognition platform after a simple β-cyclodextrin (β-CD) drop casting process. The proposed enantiomer recognition sensor has been successfully used for d and l-phenylalanine recognition. In addition, the G/D electrode can be simply regenerated by half-minute sonication due to the strong interfacial bonding between graphene and diamond. Therefore, the proposed G/D electrode showed significant potential as a reusable sensing platform for enantiomer recognition.

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6

Ciceri, Samuele, Patrizia Ferraboschi, Paride Grisenti, Shahrzad Reza Elahi, Carlo Castellano, Matteo Mori, and Fiorella Meneghetti. "(S)-Pramipexole and Its Enantiomer, Dexpramipexole: A New Chemoenzymatic Synthesis and Crystallographic Investigation of Key Enantiomeric Intermediates." Catalysts 10, no. 8 (August 16, 2020): 941. http://dx.doi.org/10.3390/catal10080941.

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A new chemoenzymatic method has been developed for the synthesis of (S)- and (R)-N-(6-hydroxy-4,5,6,7-tetrahydrobenzo[d]thiazol-2-yl) acetamide, two key synthons for the preparation of (S)-pramipexole, an anti-Parkinson drug, and its enantiomer dexpramipexole, which is currently under investigation for the treatment of eosinophil-associated disorders. These two building blocks have been obtained in good yields and high enantiomeric excess (30% and >98% ee for the R-enantiomer, and 31% and >99% ee for the S- one) through a careful optimization of the reaction conditions, starting from the corresponding racemic mixture and using two consecutive irreversible transesterifications, catalyzed by Candida antarctica lipase type A. Single crystal X-ray analysis has been carried out to unambiguously define the stereochemistry of the two enantiomers, and to explore in depth their three-dimensional features.

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7

Chanotiya, Chandan S., and Anju Yadav. "Natural Variability in Enantiomeric Composition of Bioactive Chiral Terpenoids in the Essential Oil of Solidago Canadensis L. from Uttarakhand, India." Natural Product Communications 3, no. 2 (February 2008): 1934578X0800300. http://dx.doi.org/10.1177/1934578x0800300232.

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The natural variability in the enantiomeric distribution of biologically active chiral terpenoids in Solidago canadensis L. essential oil from Kumaon was evaluated by enantioselective capillary GC, capillary GC, and GC-MS. Germacrene D, a sesquiterpene hydrocarbon, was noticed as the major compound, contributing 56.7%, 75.5% and 69.7% to the samples, while other constituents with variable compositions were limonene (0.2 to 12.5%), bornyl acetate (2.1 to 2.9%), δ-elemene (2.4 to 3.2), β-elemene (1.3 to 1.8%), and elemol (1.4 to 2.6%). The enantiomeric excess has been determined for germacrene D with (+)-enantiomer (>41.8% to >47%) dominating over the (-)-enantiomer in all the samples. Furthermore, there has been above 95% enantiomeric excess for ( R)-(+)-limonene (>95.1% to >99%), whereas moderate to low excess for (1 R)-(+)-α-pinene (>47.9%), and (1 S)-(-)-β-pinene (>30.3%) was established. Notably, only (-)-bornyl acetate was found as a single enantiomer with >99% enantiomeric excess. However, for all the identified chiral terpenoids, the enantiomeric distribution varied within only a narrow range in all the samples.

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8

Bennett, L. Lee, Paula W. Allan, Gussie Arnett, Y. Fulmer Shealy, Donna S. Shewach, William S. Mason, Isabelle Fourel, and William B. Parker. "Metabolism in Human Cells of the d and l Enantiomers of the Carbocyclic Analog of 2′-Deoxyguanosine: Substrate Activity with Deoxycytidine Kinase, Mitochondrial Deoxyguanosine Kinase, and 5′-Nucleotidase." Antimicrobial Agents and Chemotherapy 42, no. 5 (May 1, 1998): 1045–51. http://dx.doi.org/10.1128/aac.42.5.1045.

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ABSTRACT The carbocyclic analog of 2′-deoxyguanosine (CdG) has broad-spectrum antiviral activity. Because of recent observations with other nucleoside analogs that biological activity may be associated thel enantiomer rather than, as expected, with thed enantiomer, we have studied the metabolism of both enantiomers of CdG to identify the enzymes responsible for the phosphorylation of CdG in noninfected and virally infected human and duck cells. We have examined the enantiomers as substrates for each of the cellular enzymes known to catalyze phosphorylation of deoxyguanosine. Both enantiomers of CdG were substrates for deoxycytidine kinase (EC 2.7.1.74) from MOLT-4 cells, 5′-nucleotidase (EC 3.1.3.5) from HEp-2 cells, and mitochondrial deoxyguanosine kinase (EC 2.7.1.113) from human platelets and CEM cells. For both deoxycytidine kinase and mitochondrial deoxyguanosine kinase, thel enantiomer was the better substrate. Even though thed enantiomer was the preferred substrate with 5′-nucleotidase, the rate of phosphorylation of the lenantiomer was substantial. The phosphorylation of d-CdG in MRC-5 cells was greatly stimulated by infection with human cytomegalovirus. The fact that the phosphorylation of d-CdG was stimulated by mycophenolic acid and was not affected by deoxycytidine suggested that 5′-nucleotidase was the enzyme primarily responsible for its metabolism in virally infected cells.d-CdG was extensively phosphorylated in duck hepatocytes, and its phosphorylation was not affected by infection with duck hepatitis B virus. These results are of importance in understanding the mode of action of d-CdG and related analogs and in the design of new biologically active analogs.

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9

MÜller, Markus D., and Hans-Paul Bosshardt. "Enantiomer Resolution and Assay of Propionic Acid-Derived Herbicides in Formulations by Using Chiral Liquid Chromatography and Achiral Gas Chromatography." Journal of AOAC INTERNATIONAL 71, no. 3 (May 1, 1988): 614–17. http://dx.doi.org/10.1093/jaoac/71.3.614.

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Abstract Enantiomers of 6 propionic acid-derived herbicides in the form of their esters were resolved using liquid chromatography with a chiral column. Free acids are converted to methyl esters by means of a BF3- catalyzed reaction. Chromatographic resolutions for 6 of 8 herbicides investigated were in the range of 2 to 4. The method was applied for the simultaneous determination of mecoprop and 2,4-D content and individual mecoprop enantiomers in 2 formulations containing racemic and R-mecoprop in mixture with 2,4-D. Precision and accuracy of content determination was comparable to standard methods, and enantiomer contents were in good agreement with declared values. The enantiomers of dichlorprop and mecoprop were also resolved as diastereomeric menthyl esters by achiral high resolution gas chromatography (HRGC). HRGC data on enantiomer composition were in good agreement with those from the LC method and other data

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10

Li, Yan Liang, Zhong Zhen Liu, Yu Fen Huang, Lan Wei, Lian Xi Huang, Shao Hai Yang, and Zhi Xiang Fang. "Biphasic Enantioselective Partitioning of R,S-Omeprazole Enantiomers Using Chiral Extraction." Advanced Materials Research 1030-1032 (September 2014): 2334–39. http://dx.doi.org/10.4028/www.scientific.net/amr.1030-1032.2334.

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Enantioselective partitioning of racemic omeprazole enantiomers was studied using a biphasic recognition chiral extraction system. Hydrophilic hydroxypropyl-ڂ-cyclodextrin in aqueous phase and hydrophobic D-tartaric acid hexyl ester in organic phase as chiral selectors which preferentially recognize (R)-omeprazole enantiomer and (S)-omeprazole enantiomer, respectively. Different experimental variable parameters could affect the chiral extraction efficiency. The largest distribution coefficientskS,kRand separation factorځwere obtained at concentrations o f 0.1 mol/L HP-ڂ-CD and 0.2 mol/L D-tartaric acid hexyl ester, which were 47.38, 58.65 and 1.24, respectively.kRis always larger thankSwhen using different kinds of tartaric acid derivatives as chiral selectors in organic phase. The present study also reveal the mechanism of biphasic recognition chiral extraction forR,S-omeprazole enantiomers.

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11

Bayer, Ernst, Hartmut Frank, Jürgen Gerhardt, and Graeme Nicholson. "Capillary Gas Chromatographic Analysis of Amino Acids by Enantiomer Labeling." Journal of AOAC INTERNATIONAL 70, no. 2 (March 1, 1987): 234–40. http://dx.doi.org/10.1093/jaoac/70.2.234.

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Abstract The optical isomers of amino acids can be easily separated by gas chromatography using capillary columns coated with the chiral polysiloxane peptide, Chirasil-Val. Quantitative trace amino acid analysis in complex mixtures such as biological fluids, sea water, or protein hydrolysates can be achieved by enantiomer labeling: The D-amino acid enantiomers, which do not occur naturally, are added to the sample prior to analysis as internal standards. Because the D-enantiomers show the same physical and chemical properties as the natural L-enantiomers, they are ideal standard references. In routine analysis, the derivatization is achieved with a new automated derivatization robot. The D-standard serves as overall internal standard for the whole analytical procedure from sample enrichment to derivatization, chromatography, and response of the detector.

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12

Kowlessur, D., E. W. Thomas, C. M. Topham, W. Templeton, and K. Brocklehurst. "Dependence of the P2-S2 stereochemical selectivity of papain on the nature of the catalytic-site chemistry. Quantification of selectivity in the catalysed hydrolysis of the enantiomeric N-acetylphenylalanylglycine 4-nitroanilides." Biochemical Journal 266, no. 3 (March 15, 1990): 653–60. http://dx.doi.org/10.1042/bj2660653.

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1. N-Acetyl-L-phenylalanylglycine 4-nitroanilide and its D-enantiomer were synthesized and characterized and used as substrates with which to evaluate stereochemical selectivity in papain (EC 3.4.22.2)-catalysed hydrolysis. 2. Kinetic analysis at pH 6.0, I 0.1, 8.3% (v/v) NN-dimethylformamide and 25 degrees C by using initial-rate data with [S] much less than Km and weighted non-linear regression provided values of kcat./Km for the catalysed hydrolysis of both enantiomers as (kcat./Km)L = 2040 +/- 48 M-1.S-1 and (kcat./Km)D = 5.9 +/- 0.07 M-1.S-1. These data, taken together with individual values of kcat. and Km for the hydrolysis of the L-enantiomer (a) estimated in the present work as kcat. = 3.2 +/- 1.2 S-1 and Km = 1.5 +/- 0.6 mM and (b) reported by Lowe & Yuthavong [(1971) Biochem. J. 124, 107-115] for the reaction at pH 6.0 in 10% (v/v) NN-dimethylformamide and 35 degrees C, as kcat. = 1.3 +/- 0.2 S-1 and Km = 0.88 +/- 0.1 mM, suggest that (kcat./Km)L congruent to 2000 M-1.S-1 and thus that (kcat./Km)L/(kcat./Km)D congruent to 330.3. Model building indicates that both enantiomeric 4-nitroanilides can bind to papain such that the phenyl ring of the N-acetylphenylalanyl group makes hydrophobic contacts in the S2 subsite with preservation of mechanistically relevant hydrogen-bonding interactions and that the main difference is in the positioning of the beta-methylene group. 4. The dependence of P2-S2 stereochemical selectivity of papain on the nature of the catalytic-site chemistry for reactions involving derivatives of N-acetylphenylalanine is discussed. The variation in the index of stereochemical selectivity (ratio of the appropriate kinetic or thermodynamic parameter for a given pair of enantiomeric ligands), from 330 for the overall acylation process of the catalytic act, through 40 and 31 for the reaction at electrophilic sulphur in 2-pyridyl disulphides respectively without and with assistance by (His-159)-Im(+)-H, to 5 for the formation of thiohemiacetal adducts by reaction at aldehydic carbon, is interpreted in terms of the extent to which conformational variation of the bound ligand in the catalytic-site region permits the binding mode of the -CH2-Ph group of the D-enantiomer to approach that of the L-enantiomer.

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13

Gal, Joseph. "Single-Isomer Science: The Phenomenon and Its Terminology." CNS Spectrums 7, S1 (April 2002): 8–13. http://dx.doi.org/10.1017/s1092852900028546.

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ABSTRACTSingle-isomer drugs are of great importance in modern therapeutics. In this article, the basics of the underlying phenomenon are explained. Some molecules are chiral, ie, their mirror image is not superposable on the original. The most common element producing molecular chirality is a chiral center, typically a carbon atom carrying four different groups. The mirror-image molecules are termed enantiomers, but the less specific terms stereoisomers and isomers are also used. A substance consisting of only one of the two enantiomers is a single enantiomer or single isomer, and the 1:1 mixture of the enantiomers is the racemic mixture or racemate. A graphical convention that conveys the three-dimensional aspects of chiral molecules drawn in two dimensions, as well as two nongraphical conventions, based on optical rotation and configuration, are used to identify enantiomers. Optical rotation is a physical property of single enantiomers and involves rotation of the plane of plane-polarized light, each pure enantiomer rotating with equal magnitude but in the opposite direction (dextro and levo). Configuration is the actual arrangement in space of the atoms of chiral molecules. Two systems of indicating configuration are in use. One employs D and L to denote the respective enantiomers, and is applicable only to α-amino acids and carbohydrates. The other is a universal system using R and S as descriptors for the two possible arrangements, respectively, of the atoms around the chiral center. Interest in chiral drugs stems from the frequently observed biological differences between enantiomers. Such enantioselectivity is the result of different interactions of the drug enantiomers with target receptors that are themselves chiral and single-enantiomeric.

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14

Baek, Judy, and Subramaniam Pennathur. "Urinary 2-Hydroxyglutarate Enantiomers Are Markedly Elevated in a Murine Model of Type 2 Diabetic Kidney Disease." Metabolites 11, no. 8 (July 21, 2021): 469. http://dx.doi.org/10.3390/metabo11080469.

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Metabolic reprogramming is a hallmark of diabetic kidney disease (DKD); nutrient overload leads to increased production of metabolic byproducts that may become toxic at high levels. One metabolic byproduct may be 2-hydroxyglutarate (2-HG), a metabolite with many regulatory functions that exists in both enantiomeric forms physiologically. We quantitatively determined the levels of L and D-2HG enantiomers in the urine, plasma, and kidney cortex of db/db mice, a pathophysiologically relevant murine model of type 2 diabetes and DKD. We found increased fractional excretion of both L and D-2HG enantiomers, suggesting increased tubular secretion and/or production of the two metabolites in DKD. Quantitation of TCA cycle metabolites in db/db cortex suggests that TCA cycle overload and an increase in 2-HG precursor substrate, α-ketoglutarate, drive the increased L and D-2HG production in DKD. In conclusion, we demonstrated increased 2-HG enantiomer production and urinary excretion in murine type 2 DKD, which may contribute to metabolic reprogramming and progression of diabetic kidney disease.

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15

Cooper, George, and Andro C. Rios. "Enantiomer excesses of rare and common sugar derivatives in carbonaceous meteorites." Proceedings of the National Academy of Sciences 113, no. 24 (May 31, 2016): E3322—E3331. http://dx.doi.org/10.1073/pnas.1603030113.

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Biological polymers such as nucleic acids and proteins are constructed of only one—the d or l—of the two possible nonsuperimposable mirror images (enantiomers) of selected organic compounds. However, before the advent of life, it is generally assumed that chemical reactions produced 50:50 (racemic) mixtures of enantiomers, as evidenced by common abiotic laboratory syntheses. Carbonaceous meteorites contain clues to prebiotic chemistry because they preserve a record of some of the Solar System’s earliest (∼4.5 Gy) chemical and physical processes. In multiple carbonaceous meteorites, we show that both rare and common sugar monoacids (aldonic acids) contain significant excesses of the d enantiomer, whereas other (comparable) sugar acids and sugar alcohols are racemic. Although the proposed origins of such excesses are still tentative, the findings imply that meteoritic compounds and/or the processes that operated on meteoritic precursors may have played an ancient role in the enantiomer composition of life’s carbohydrate-related biopolymers.

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16

Mann, Lea, Markus Lang, Philipp Schulze, Jan Henrik Halz, René Csuk, Sophie Hoenke, Rüdiger W. Seidel, and Adrian Richter. "Racemization-free synthesis of Nα-2-thiophenoyl-phenylalanine-2-morpholinoanilide enantiomers and their antimycobacterial activity." Amino Acids 53, no. 8 (July 14, 2021): 1187–96. http://dx.doi.org/10.1007/s00726-021-03044-1.

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AbstractNα-2-thiophenoyl-d-phenylalanine-2-morpholinoanilide (MMV688845, IUPAC: N-(1-((2-morpholinophenyl)amino)-1-oxo-3-phenylpropan-2-yl)thiophene-2-carboxamide) from the Pathogen Box® library (Medicines for Malaria Ventures, MMV) is a promising lead compound for antimycobacterial drug development. Two straightforward synthetic routes to the title compound starting from phenylalanine or its Boc-protected derivative are reported. Employing Boc-phenylalanine as starting material and the T3P® and PyBOP® amide coupling reagents enables racemization-free synthesis, avoiding the need for subsequent separation of the enantiomers. The crystal structure of the racemic counterpart gives insight into the molecular structure and hydrogen bonding interactions in the solid state. The R-enantiomer of the title compound (derived from d-phenylalanine) exhibits activity against non-pathogenic and pathogenic mycobacterial strains, whereas the S-enantiomer is inactive. Neither of the enantiomers and the racemate of the title compound shows cytotoxicity against various mammalian cells.

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17

Urban, Jennifer M., Janson Ho, Gavin Piester, Riqiang Fu, and Bradley L. Nilsson. "Rippled β-Sheet Formation by an Amyloid-β Fragment Indicates Expanded Scope of Sequence Space for Enantiomeric β-Sheet Peptide Coassembly." Molecules 24, no. 10 (May 23, 2019): 1983. http://dx.doi.org/10.3390/molecules24101983.

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In 1953, Pauling and Corey predicted that enantiomeric β-sheet peptides would coassemble into so-called “rippled” β-sheets, in which the β-sheets would consist of alternating l- and d-peptides. To date, this phenomenon has been investigated primarily with amphipathic peptide sequences composed of alternating hydrophilic and hydrophobic amino acid residues. Here, we show that enantiomers of a fragment of the amyloid-β (Aβ) peptide that does not follow this sequence pattern, amyloid-β (16–22), readily coassembles into rippled β-sheets. Equimolar mixtures of enantiomeric amyloid-β (16–22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated β-sheet fibrils. Formation of rippled β-sheets composed of alternating l- and d-amyloid-β (16–22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled β-sheet formation by l- and d-amyloid-β (16–22) is energetically favorable relative to self-assembly into corresponding pleated β-sheets. This work illustrates that coassembly of enantiomeric β-sheet peptides into rippled β-sheets is not limited to peptides with alternating hydrophobic/hydrophilic sequence patterns, but that a broader range of sequence space is available for the design and preparation of rippled β-sheet materials.

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18

Valverde, Serafin, Bernardo Herradon, Rosa M. Rabanal, and Manuel Martin-Lomas. "The synthesis of D-asperlin." Canadian Journal of Chemistry 65, no. 2 (February 1, 1987): 339–42. http://dx.doi.org/10.1139/v87-057.

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19

Pohanka, Miroslav. "D-Lactic Acid as a Metabolite: Toxicology, Diagnosis, and Detection." BioMed Research International 2020 (June 18, 2020): 1–9. http://dx.doi.org/10.1155/2020/3419034.

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Two enantiomers of lactic acid exist. While L-lactic acid is a common compound of human metabolism, D-lactic acid is produced by some strains of microorganism or by some less relevant metabolic pathways. While L-lactic acid is an endogenous compound, D-lactic acid is a harmful enantiomer. Exposure to D-lactic acid can happen by various ways including contaminated food and beverages and by microbiota during some pathological states like short bowel syndrome. The exposure to D-lactic acid cannot be diagnosed because the common analytical methods are not suitable for distinguishing between the two enantiomers. In this review, pathways for D-lactic acid, pathological processes, and diagnostical and analytical methods are introduced followed by figures and tables. The current literature is summarized and discussed.

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20

QU, Ning, Natalia A. IGNATENKO, Phillip YAMAUCHI, David E. STRINGER, Corey LEVENSON, Patrick SHANNON, Scott PERRIN, and Eugene W. GERNER. "Inhibition of human ornithine decarboxylase activity by enantiomers of difluoromethylornithine." Biochemical Journal 375, no. 2 (October 15, 2003): 465–70. http://dx.doi.org/10.1042/bj20030382.

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Racemic difluoromethylornithine (d/l-DFMO) is an inhibitor of ODC (ornithine decarboxylase), the first enzyme in eukaryotic polyamine biosynthesis. d/l-DFMO is an effective anti-parasitic agent and inhibitor of mammalian cell growth and development. Purified human ODC-catalysed ornithine decarboxylation is highly stereospecific. However, both DFMO enantiomers suppressed ODC activity in a time- and concentration-dependent manner. ODC activity failed to recover after treatment with either l- or d-DFMO and dialysis to remove free inhibitor. The inhibitor dissociation constant (KD) values for the formation of enzyme–inhibitor complexes were 28.3±3.4, 1.3±0.3 and 2.2±0.4 μM respectively for d-, l- and d/l-DFMO. The differences in these KD values were statistically significant (P<0.05). The inhibitor inactivation constants (Kinact) for the irreversible step were 0.25±0.03, 0.15±0.03 and 0.15±0.03 min−1 respectively for d-, l- and d/l-DFMO. These latter values were not statistically significantly different (P>0.1). d-DFMO was a more potent inhibitor (IC50~7.5 μM) when compared with d-ornithine (IC50~1.5 mM) of ODC-catalysed l-ornithine decarboxylation. Treatment of human colon tumour-derived HCT116 cells with either l- or d-DFMO decreased the cellular polyamine contents in a concentration-dependent manner. These results show that both enantiomers of DFMO irreversibly inactivate ODC and suggest that this inactivation occurs by a common mechanism. Both enantiomers form enzyme–inhibitor complexes with ODC, but the probability of formation of these complexes is 20 times greater for l-DFMO when compared with d-DFMO. The rate of the irreversible reaction in ODC inactivation is similar for the l- and d-enantiomer. This unexpected similarity between DFMO enantiomers, in contrast with the high degree of stereospecificity of the substrate ornithine, appears to be due to the α-substituent of the inhibitor. The d-enantiomer may have advantages, such as decreased normal tissue toxicity, over l- or d/l-DFMO in some clinical applications.

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21

Bennett, Brian M., Jake W. Kempenaar, L. Douglas Hayward, and Romy Baur. "Pharmacokinetic–hemodynamic studies of the enantiomers of isoidide dinitrate in conscious rats." Canadian Journal of Physiology and Pharmacology 69, no. 9 (September 1, 1991): 1277–83. http://dx.doi.org/10.1139/y91-187.

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Our objective was to determine the pharmacokinetic properties of the D- and L-enantiomers of isoidide dinitrate (IIDN) in relation to their hemodynamic effects. Conscious male Sprague–Dawley rats were administered a bolus i.v. dose of 2 mg∙kg−1D- or L-IIDN and simultaneous blood samples and blood pressure recordings were taken at various times. The elimination half-life of D-IIDN was significantly shorter than that of L-IIDN (10 vs. 16 min) owing to a larger Vd area of the L-enantiomer (5.8 vs. 3.8 L∙kg−1). The plasma clearance of either enantiomer was approximately 250 mL∙min−1∙kg−1 a value equal to plasma cardiac output. The pharmacokinetic data indicates that IIDN is distributed extensively and that significant extrahepatic biotransformation of the drug occurs. After intravenous administration of D-IIDN, there was an initial decrease in mean arterial pressure (MAP) of 29% compared with 15% for L-IIDN (p < 0.05). For L-IIDN, the decrease in MAP was short lived (less than 2 min), while for D-IIDN, MAP remained significantly decreased for up to 60 min. The oral bioavailability of both enantiomers was low (ca. 7%). However, decreases in MAP occurred after oral administration of D-IIDN, suggesting that the mononitrate metabolite of IIDN was pharmacologically active. We conclude that, despite a faster rate of elimination from the central compartment, D-IIDN exhibits a greater vasodilator effect in the intact animal compared to L-IIDN. This is consistent with previous observations of a 10-fold greater potency of D-IIDN for relaxation of isolated vascular smooth muscle.Key words: organic nitrates, isoidide dinitrate, enantiomers, pharmacokinetics, hemodynamics.

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22

Kraft, Jochen, Martin Golkowski, and Thomas Ziegler. "Spiro-fused carbohydrate oxazoline ligands: Synthesis and application as enantio-discrimination agents in asymmetric allylic alkylation." Beilstein Journal of Organic Chemistry 12 (January 29, 2016): 166–71. http://dx.doi.org/10.3762/bjoc.12.18.

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In the present work, we describe a convenient synthesis of spiro-fused D-fructo- and D-psico-configurated oxazoline ligands and their application in asymmetric catalysis. The ligands were synthesized from readily available 3,4,5-tri-O-benzyl-1,2-O-isopropylidene-β-D-fructopyranose and 3,4,5-tri-O-benzyl-1,2-O-isopropylidene-β-D-psicopyranose, respectively. The latter compounds were partially deprotected under acidic conditions followed by condensation with thiocyanic acid to give an anomeric mixture of the corresponding 1,3-oxazolidine-2-thiones. The anomeric 1,3-oxazolidine-2-thiones were separated after successive benzylation, fully characterized and subjected to palladium catalyzed Suzuki–Miyaura coupling with 2-pyridineboronic acid N-phenyldiethanolamine ester to give the corresponding 2-pyridyl spiro-oxazoline (PyOx) ligands. The spiro-oxazoline ligands showed high asymmetric induction (up to 93% ee) when applied as chiral ligands in palladium-catalyzed allylic alkylation of 1,3-diphenylallyl acetate with dimethyl malonate. The D-fructo-PyOx ligand provided mainly the (R)-enantiomer while the D-psico-configurated ligand gave the (S)-enantiomer with a lower enantiomeric excess.

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23

Kuzeff, R. M. "A Review of Use of Enantiomers in Homeopathy." ISRN Toxicology 2012 (August 15, 2012): 1–22. http://dx.doi.org/10.5402/2012/575292.

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This paper reviews publications of laboratory experiments using pairs of enantiomers in homeopathy. Many molecules in nature have geometry which enables them to exist as nonsuperimposable mirror images or enantiomers. Modulation of toxicity of such molecules provides possibility for therapeutics, since they target multiple points in biochemical pathways. It was hypothesized that toxicity of a chemical agent could be counteracted by a homeopathic preparation of the enantiomer of the chemical agent (patents applied for: PCT/AU2003/000219-PCT/AU2008/001611). A diverse body of data, including controlled laboratory studies, supports the conclusion that toxicity of optical isomers may be inhibited by homeopathic enantiomer preparations. These data were obtained with minimal or no pretesting to determine optimal test solutions. Inhibition of the excitotoxic neurotransmitter L-glutamic acid with homeopathic preparations of D-glutamic acid indicates the latter may be of use for amelioration of symptoms of disturbances of mood. Similarly, homeopathic preparation of (+)-nicotine may be of use for inhibition of effects of nicotine in tobacco.

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24

Gao, Li Ping, Wen Juan Li, and Xin Ping Wang. "A Validated Chiral HPLC Method for the Enantiomeric Separation of Melphalan HCl." Advanced Materials Research 781-784 (September 2013): 993–98. http://dx.doi.org/10.4028/www.scientific.net/amr.781-784.993.

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A new and accurate chiral HPLC method was developed for the determination of Melphalan HCl, L-Phenylalanine, 4-bis (2-chloroethyl) amino hydrochloride an anti-cancer chemotherapy drug and its potential impurity namely D-Phenylalanine, 4-bis (2-chloroethyl) amino hydrochloride ( D-enantiomer) in bulk substance. HPLC separation was carried out by reverse phase chromatography on Crownpak CR (+) (5μm, 4.0x150mm) with a mobile phase composed of perchloric acid (pH 4.0): methanol in the ratio of 90:10. Melphalan and its potential impurities were baseline resolved in the optimized method. The pH of perchloric acid solution in the mobile phase has played a key role in achieving chromatographic resolution between the enantiomers and in enhancing chromatographic efficiency. The developed method was completely validated and proved to be robust. The validated method yielded good results regarding specificity, precision, linearity, accuracy, robustness, sensitivity. Melphalan HCl sample solution is found to be stable for at least 60hrs at room temperature. The proposed method was found to be suitable and accurate for quantitative determination of Melphalan HCl and its D-enantiomer in bulk substance.

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25

Küsters, Ernst, and Willy Rahmen. "Allo-Verbindungen mit ungewöhnlichem Verhalten bei der Gaschromatographie an chiraler stationärer Phase / Allo-Compounds with Unusual Behaviour in Gas Chromatography Using Chiral Stationary Phase." Zeitschrift für Naturforschung B 43, no. 5 (May 1, 1988): 619–22. http://dx.doi.org/10.1515/znb-1988-0522.

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Abstract The Separation of the enantiomers of D,L-allo-threoninol, necessary in racemization studies of peptide hydrolysates, gave a surprising result with respect to the elution series of the antipodes. Contrary to the rule (L before D on Chirasil-L-Val) D-allo-threoninol is eluted before its mirror image. This behaviour can only be explained by the differing importance of the asymmetric centres contained in the molecule. As a result of this and taking into account the chromatographic behaviour of allo-compounds refined model concepts of enantiomer separation must be devel-oped in future.The separation of allo-compounds of threonine, isoleucine and cystathionine is considered from this aspect.

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26

Gati, W. P., A. N. Lin, T. I. Wang, J. D. Young, and A. R. P. Paterson. "Parasite-induced processes for adenosine permeation in mouse erythrocytes infected with the malarial parasite Plasmodium yoelii." Biochemical Journal 272, no. 1 (November 15, 1990): 277–80. http://dx.doi.org/10.1042/bj2720277.

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In mouse erythrocytes harbouring the malarial parasite Plasmodium yoelii, three processes contributed to inward fluxes of adenosine, one of which is attributed to the native nucleoside transporter, because of the inhibitory effects of nitrobenzylthioinosine (NBMPR). New (parasite-induced) permeation processes of low NBMPR-sensitivity were (i) saturable fluxes with preference for the D enantiomer (D-Ado) and (ii) apparently unsaturable fluxes that proceeded by a channel-like route without enantiomeric selectivity. Parasite-induced fluxes of L- and D-Ado were similarly inhibited by furosemide [IC50 (concn. causing half-maximal inhibition) 15-17 microM], whereas D-Ado fluxes in uninfected erythrocytes were 10-fold less sensitive.

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27

Zagami, Roberto, Maria Angela Castriciano, Andrea Romeo, and Luigi Monsù Scolaro. "Spectroscopic investigations on chiral J-aggregates induced by tartaric acid in alcoholic solution." Journal of Porphyrins and Phthalocyanines 21, no. 04-06 (April 2017): 327–33. http://dx.doi.org/10.1142/s1088424617500183.

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Chiral J-aggregates of meso-tetrakis(4-sulfonatophenyl)porphyrin (TPPS[Formula: see text] have been obtained in ethanol solution triggered by addition of both enantiomeric forms of tartaric acid. A detailed spectroscopic investigation has been performed on aggregates obtained by a well-defined mixture protocol of reactants. Our findings show as both aggregation process and induced supramolecular chirality essentially depend on the concentration of the reactants. Contrary to what occurs in aqueous solution, TPPS4 in ethanol solution shows: (i) at low porphyrin concentration, an aggregation behavior characterized by a L-tartaric acid threshold whereas the D-tartaric does not work even at high concentrations, so revealing an enantiomeric discrimination; (ii) at high porphyrin concentration, a large kinetic discrimination of D- vs. L-enantiomer.

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28

Yamamoto, Taiji, Keisuke Yaku, and Takashi Nakagawa. "Simultaneous Measurement of Amino Acid Enantiomers in Aged Mouse Brain Samples by LC/MS/MS Combined with Derivatization Using Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA)." Metabolites 11, no. 1 (January 15, 2021): 57. http://dx.doi.org/10.3390/metabo11010057.

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d-amino acids have distinct roles from their l-enantiomer. In particular, some d-amino acids function as agonists or antagonists of neuronal receptors and are involved in higher brain functions. Thus, it is important to precisely measure the levels of these amino acid enantiomers in cells and tissues. Various quantification methods have been developed for measurements of chiral amino acids. However, each method has advantages and disadvantages. Additionally, measuring the amino acid enantiomers in crude biological samples requires a higher selectivity. In this study, we developed a quantification method for amino acid enantiomers using derivatization with Nα-(5-Fluoro-2,4-dinitrophenyl)-l-leucinamide (l-FDLA) followed by liquid chromatography–tandem mass spectrometry (LC/MS/MS) with a conventional reversed-phase column. We simultaneously identified 10 chiral amino acids. Furthermore, we applied this method to investigate murine tissue samples and examined the effect of aging on the amino acid levels in aged brain regions. We found that aging decreased the levels of both d-serine and d-aspartate in the hippocampus. In addition, d-Phenylalanine in the thalamus significantly increased with age. In conclusion, our method is suitable for the quantification of the d-amino acids in crude biological samples and may contribute to elucidating the biological roles of chiral amino acids.

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Stewart, David H., L. Douglas Hayward, and Brian M. Bennett. "Differential biotransformation of the enantiomers of isoidide dinitrate in isolated rat aorta." Canadian Journal of Physiology and Pharmacology 67, no. 11 (November 1, 1989): 1403–8. http://dx.doi.org/10.1139/y89-225.

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Previous studies have demonstrated that the D-enantiomer of isoidide dinitrate (IIDN) is 10-fold more potent than the L-enantiomer for relaxation and cyclic GMP accumulation in isolated rat aorta. To test whether preferential biotransformation of D-IIDN to a species that activates guanylate cyclase is the basis for this observed enantioselectivity, paired segments of rat aorta were exposed to D- and L-IIDN and the tissue accumulation of the parent compound and the formation of their respective metabolites (D- and L-isoidide mononitrate, IIMN) were determined. The extent of relaxation of rat aorta following exposure to 2 μM D-IIDN was greater than that by L-IIDN over a 5-minute time course, and this was associated with a higher rate of D-IIDN biotransformation to D-IIMN at all time points. In addition, the rate of D-IIDN biotransformation was greater than that of L-IIDN at most IIDN concentrations tested. By contrast, the amount of D- and L-IIDN in the tissue was the same at all time points and concentrations tested, indicating that selective uptake of D-IIDN into blood vessels did not occur. When tissues were made tolerant to organic nitrate-induced relaxation by treatment with a high concentration of glyceryl trinitrate, the biotransformation of both D- and L-IIDN was attenuated. This suggests that mechanism-based biotransformation may be affected during tolerance development. Furthermore, the association of preferential D-IIDN biotransformation with its greater potency for vasodilation and cyclic GMP accumulation suggests than an enantioselective site for biotransformation is an important component of organic nitrate-induced vasodilation.Key words: biotransformation, vascular smooth muscle, organic nitrates, isoidide dinitrate, enantiomers.

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30

Victoria, Florence, John Manioudakis, Liana Zaroubi, Brandon Findlay, and Rafik Naccache. "Tuning residual chirality in carbon dots with anti-microbial properties." RSC Advances 10, no. 53 (2020): 32202–10. http://dx.doi.org/10.1039/d0ra05208f.

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Chiral carbon dots, prepared from the unnatural d-enantiomer of cysteine, inhibit the growth of Escherichia coli ATCC 25922 and MG1655 at a lower concentration than l-carbon dots, prepared from the l-enantiomer.

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31

Salom, S. M., R. F. Billings, W. W. Upton, M. J. Dalusky, D. M. Grosman, T. L. Payne, C. W. Berisford, and T. N. Shaver. "Effect of verbenone enantiomers and racemic endo-brevicomin on response of Dendroctonusfrontalis (Coleoptera: Scolytidae) to attractant-baited traps." Canadian Journal of Forest Research 22, no. 7 (July 1, 1992): 925–31. http://dx.doi.org/10.1139/x92-123.

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Different enantiomeric ratios and elution rates of the inhibitor pheromones verbenone and racemic endo-brevicomin were evaluated for their effects on the numerical response of the southern pine beetle, Dendroctonusfrontalis Zimm., to attractant-baited traps. Enantiomeric ratios and elution rates of verbenone were important factors in inhibiting response of male D. frontalis. Deterrence was most effective for enantiomeric ratios of verbenone containing 34 and 50% of the (+) enantiomer. Using a 34% (+): 66% (−) mixture of verbenone, the number of male D. frontalis captured in attractant-baited traps declined as elution rates increased from 4.2 to 12.5 mg/h. None of the enantiomeric ratios or elution rates of verbenone tested consistently influenced female response. endo-Brevicomin added to attractant-baited traps reduced catches of male D. frontalis, but did not significantly reduce catches further when added to traps also emitting verbenone. Female catches were not reduced significantly by the presence of endo-brevicomin. Numerical responses of the predatory beetle Thanasimusdubius Fab. are generally unaffected by the presence of verbenone alone or in combination with endo-brevicomin.

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32

Zipper, Christian, Monika Bunk, Alexander J. B. Zehnder, and Hans-Peter E. Kohler. "Enantioselective Uptake and Degradation of the Chiral Herbicide Dichlorprop [(RS)-2-(2,4-Dichlorophenoxy)propanoic acid] by Sphingomonas herbicidovorans MH." Journal of Bacteriology 180, no. 13 (July 1, 1998): 3368–74. http://dx.doi.org/10.1128/jb.180.13.3368-3374.1998.

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ABSTRACT Sphingomonas herbicidovorans MH was able to completely degrade both enantiomers of the chiral herbicide dichlorprop [(RS)-2-(2,4-dichlorophenoxy)propanoic acid], with preferential degradation of the (S) enantiomer over the (R) enantiomer. These results are in agreement with the recently reported enantioselective degradation of mecoprop [(RS)-2-(4-chloro-2-methylphenoxy)propanoic acid] by this bacterium (C. Zipper, K. Nickel, W. Angst, and H.-P. E. Kohler, Appl. Environ. Microbiol. 62:4318–4322, 1996). Uptake of (R)-dichlorprop, (S)-dichlorprop, and 2,4-D (2,4-dichlorophenoxyacetic acid) was inducible. Initial uptake rates of cells grown on the respective substrate showed substrate saturation kinetics with apparent affinity constants (Kt ) of 108, 93, and 117 μM and maximal velocities (V max) of 19, 10, and 21 nmol min−1 mg of protein−1 for (R)-dichlorprop, (S)-dichlorprop, and 2,4-D, respectively. Transport of (R)-dichlorprop, (S)-dichlorprop, and 2,4-D was completely inhibited by various uncouplers and by nigericin but was only marginally inhibited by valinomycin and by the ATPase inhibitorN,N′-dicyclohexylcarbodiimine. Experiments on the substrate specificity of the putative transport systems revealed that (R)-dichlorprop uptake was inhibited by (R)-mecoprop but not by (S)-mecoprop, (S)-dichlorprop, or 2,4-D. On the other hand, the (S)-dichlorprop transport was inhibited by (S)-mecoprop but not by (R)-mecoprop, (R)-dichlorprop, or 2,4-D. These results provide evidence that the first step in the degradation of dichlorprop, mecoprop, and 2,4-D by S. herbicidovorans is active transport and that three inducible, proton gradient-driven uptake systems exist: one for (R)-dichlorprop and (R)-mecoprop, another for (S)-dichlorprop and (S)-mecoprop, and a third for 2,4-D.

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33

Pettigrew, Jeremy D., Rebecca P. Freeman, and Peter D. Wilson. "Total synthesis of ()-xyloketal D and its enantiomer Confirmation of absolute stereochemistry." Canadian Journal of Chemistry 82, no. 11 (November 1, 2004): 1640–48. http://dx.doi.org/10.1139/v04-138.

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The total synthesis of ()-xyloketal D and its enantiomer have been achieved by the reaction of an ortho-quinone methide with (4R)- and (4S)-4,5-dihydro-2,4-dimethylfuran via a diastereoselective inverse electron demand DielsAlder reaction. This total synthesis confirmed the absolute stereochemistry of the natural product. The ortho-quinone methide was generated by reaction of an appropriately functionalized Mannich base with methyl iodide. The Mannich base was prepared in one step from 2,4-dihydroxyacetophenone, formaldehyde, and morpholine. The enantiomeric dihydrofurans were prepared from (2R)- and (2S)-2-methylpent-4-ynoic acid via a three-step reaction sequence. These chiral nonracemic synthetic precursors were prepared from the corresponding (R)-phenylglycinol-derived diastereomeric amides of the readily available racemic carboxylic acid. The absolute stereochemistry of these carboxylic acids was firmly established by conversion to a known compound that had been previously prepared from a chiral pool starting material.Key words: xyloketal D, inverse electron demand DielsAlder reaction, ortho-quinone methide, dihydrofuran.

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34

Templeton, W., D. Kowlessur, E. W. Thomas, C. M. Topham, and K. Brocklehurst. "A re-appraisal of the structural basis of stereochemical recognition in papain. Insensitivity of binding-site-catalytic-site signalling to P2-chirality in a time-dependent inhibition." Biochemical Journal 266, no. 3 (March 15, 1990): 645–51. http://dx.doi.org/10.1042/bj2660645.

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1. 2-(N'-Acetyl-D-phenylalanylamino)ethyl 2′-pyridyl disulphide (compound I) [m.p. 123-124 degrees C; [alpha]20D -7.1 degrees (c 0.042 in methanol)] was synthesized, and the results of a study of the pH-dependence of the second-order rate constant (k) for its reaction with the catalytic-site thiol group of papain (EC 3.4.22.2), together with existing kinetic data for the analogous reaction of the L-enantiomer (compound II), were used to evaluate the consequences for transition-state geometry of the difference in chirality at the P2 position of the probe molecule. 2. The kinetic data suggest that the D-enantiomer binds approx. 40-fold less tightly to papain than the L-enantiomer but that the binding-site-catalytic-site signalling that results in a (His-159)-Im(+)-H-assisted transition state occurs equally effectively in the interaction of the former probe as in that of the latter. This results in pH-k profiles for the reactions of both enantiomers each characterized by four macroscopic pKa values (3.7-3.9, 4.1-4.3, 7.9-8.3 and 9.4-9.5) in which k is maximal at pH approx. 6 where the -Im(+)-H-assisted transition state is most fully developed. 3. Model building indicates that both enantiomers can bind to papain such that the phenyl ring of the N-acetylphenylalanyl group makes hydrophobic contacts in the binding pocket of the S2 subsite with preservation of the three hydrogen-bonding interactions involving the substrate analogue reagent and (Asp-158) C = O, (Gly-66) C = O, and (Gly-66)-N-H of papain. Earlier predictions that binding of N-acyl-D-phenylalanine derivatives to papain would be prevented on steric grounds [Berger & Schechter (1970) Philos. Trans. R. Soc. London B 257, 249-264; Lowe & Yuthavong (1971) Biochem. J. 124, 107-115; Lowe (1976) Tetrahedron 32, 291-302] were based on assumed models that are not consistent with the X-ray-diffraction data for papain inhibited by alkylation of Cys-25 with N-benzyloxycarbonyl-Phe-Ala-chloromethane [Drenth, Kalk & Swen (1976) Biochemistry 15, 3731-3738]. 4. The possibility that the kinetic expression of P2-S2 stereospecificity may depend on the nature of the chemistry occurring in the catalytic site of papain is discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

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35

Uta, Daisuke, Kohei Koga, Hidemasa Furue, Keiji Imoto, and Megumu Yoshimura. "L-bupivacaine Inhibition of Nociceptive Transmission in Rat Peripheral and Dorsal Horn Neurons." Anesthesiology 134, no. 1 (November 9, 2020): 88–102. http://dx.doi.org/10.1097/aln.0000000000003596.

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Background Although the widely used single L-enantiomers of local anesthetics have less toxic effects on the cardiovascular and central nervous systems, the mechanisms mediating their antinociceptive actions are not well understood. The authors hypothesized that significant differences in the ion channel blocking abilities of the enantiomers of bupivacaine would be identified. Methods The authors performed electrophysiologic analysis on rat dorsal root ganglion neurons in vitro and on spinal transmissions in vivo. Results In the dorsal root ganglion, these anesthetics decreased the amplitudes of action potentials. The half-maximum inhibitory concentrations of D-enantiomer D-bupivacaine were almost equal for Aβ (29.5 μM), Aδ (29.7μM), and C (29.8 μM) neurons. However, the half-maximum inhibitory concentrations of L-bupivacaine was lower for Aδ (19.35 μM) and C (19.5 μM) neurons than for A β (79.4 μM) neurons. Moreover, D-bupivacaine almost equally inhibited tetrodotoxin-resistant (mean ± SD: 15.8 ± 10.9% of the control, n = 14, P < 0.001) and tetrodotoxin-sensitive (15.4 ± 15.6% of the control, n = 11, P = 0.004) sodium currents. In contrast, L-bupivacaine suppressed tetrodotoxin-resistant sodium currents (26.1 ± 19.5% of the control, n = 18, P < 0.001) but not tetrodotoxin-sensitive sodium currents (74.5 ± 18.2% of the control, n = 11, P = 0.477). In the spinal dorsal horn, L-bupivacaine decreased the area of pinch-evoked excitatory postsynaptic currents (39.4 ± 11.3% of the control, n = 7, P < 0.001) but not touch-evoked responses (84.2 ± 14.5% of the control, n = 6, P = 0.826). In contrast, D-bupivacaine equally decreased pinch- and touch-evoked responses (38.8 ± 9.5% of the control, n = 6, P = 0.001, 42.9 ± 11.8% of the control, n = 6, P = 0.013, respectively). Conclusions These results suggest that the L-enantiomer of bupivacaine (L-bupivacaine) effectively inhibits noxious transmission to the spinal dorsal horn by blocking action potential conduction through C and Aδ afferent fibers. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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36

Rohokale, Rajendra S., and Dilip D. Dhavale. "Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin." Beilstein Journal of Organic Chemistry 10 (March 17, 2014): 667–71. http://dx.doi.org/10.3762/bjoc.10.59.

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A directed manipulation of the functional groups at C3 and C4 of D-glucose was demonstrated to synthesize naturally occurring (2S,3R)-α-hydroxy-β-aminodecanoic acid (AHDA, 2a) and its enantiomer 2b. The enantiomer of 2a is the N-terminal part of the natural linear pentapeptide microginin, which is used as an antihypertensive agent.

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37

Conway, Stuart J., Jan W. Thuring, Sylvain Andreu, Brynn T. Kvinlaug, H. Llewelyn Roderick, Martin D. Bootman, and Andrew B. Holmes. "The Synthesis of Membrane Permeant Derivatives of myo-Inositol 1,4,5-Trisphosphate." Australian Journal of Chemistry 59, no. 12 (2006): 887. http://dx.doi.org/10.1071/ch06357.

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In order to enable the study of the intracellular second messenger d-myo-inositol 1,4,5-trisphosphate (InsP3) and its receptors (InsP3Rs), it has been desirable to develop protected derivatives of InsP3 that are able to enter the cell, upon extracellular application. The subsequent removal of the lipophilic protecting groups, by intracellular enzymes, releases InsP3 and leads to the activation of InsP3Rs. Two syntheses of d-myo-inositol 1,4,5-trisphosphate hexakis(butyryloxymethyl) ester (d-InsP3/BM) and one of l-InsP3/BM are reported. It is demonstrated that extracellular application of the d-enantiomer results in Ca2+ release, which is thought to occur via InsP3Rs. Application of the l-enantiomer resulted in little Ca2+ release.

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Xhonneux, Raymond, Luc Wouters, Robert S. Reneman, and Paul A. J. Janssen. "The l-enantiomer of nebivolol potentiates the blood pressure lowering effect of the d-enantiomer." European Journal of Pharmacology 181, no. 3 (June 1990): 261–65. http://dx.doi.org/10.1016/0014-2999(90)90087-m.

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39

Molins, Elies, and Josep Coll. "Lupulin structures revisited." Acta Crystallographica Section C Crystal Structure Communications 65, no. 3 (February 7, 2009): e11-e12. http://dx.doi.org/10.1107/s0108270108000309.

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The crystal structures of lupulin A, C30H46O11, and lupulin D, C25H38O8, should both display the neoclerodane skeleton, but the deposited atomic coordinates of lupulin D correspond to the inverted enantiomer.

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40

VERRI, Annalisa, Giuseppina PRIORI, Silvio SPADARI, Luisa TONDELLI, and Federico FOCHER. "Relaxed enantioselectivity of human mitochondrial thymidine kinase and chemotherapeutic uses of L-nucleoside analogues." Biochemical Journal 328, no. 1 (November 15, 1997): 317–20. http://dx.doi.org/10.1042/bj3280317.

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Our discovery that Herpes virus thymidine kinase (TK) and cellular deoxycytidine kinase lack enantioselectivity, being able to phosphorylate both D- and L-enantiomers of the substrate, suggested the use of unnatural L-nucleoside analogues as antiviral drugs (Herpes, hepatitis and immunodeficiency viruses). Several L-nucleoside analogues have displayed a short-term cytotoxicity much lower than their corresponding D-counterpart. Since the delayed cytotoxicity of a drug often depends on its effects on mitochondrial metabolism, we have investigated the degree of enantioselectivity of human mitochondrial thymidine kinase (mt-TK). We demonstrate that mt-TK does not show an absolute enantioselectivity, being able to recognize, although with lower efficiency, the L-enantiomers of thymidine, deoxycytidine and modified deoxyuridines, such as (E)-5-(2-bromovinyl)-2ʹ-deoxyuridine and 5-iodo-2ʹ-deoxyuridine. Interestingly, the reported negative co-operativity of mt-TK phosphorylating β-D-2ʹ-deoxythymidine (D-Thd), disappears when the deoxyribose moiety has the inverted configuration, resulting in the preferential phosphorylation of D-Thd even in the presence of high concentrations of the L-enantiomer. This, coupled with the higher Km for β-l-2ʹ-deoxythymidine (L-Thd), makes mt-TK resistant to high concentrations of L-Thd and L-Thd analogues, minimizing the mitochondria-dependent delayed cytotoxicity that might be caused by the administration of l-nucleoside analogues as antivirals.

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Kirchhoefer, Ross D., Gerard M. Sullivan, and James F. Allgire. "Analysis of USP Epinephrine Injections for Potency, Impurities, Degradation Products, and d-Enantiomer by Liquid Chromatography, Using Ultraviolet and Electrochemical Detectors." Journal of AOAC INTERNATIONAL 68, no. 2 (March 1, 1985): 163–65. http://dx.doi.org/10.1093/jaoac/68.2.163.

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Abstract A liquid chromatographic (LC) method was adapted for the determination of epinephrine and related impurities in intravenous and cardiac injections; ultraviolet (UV) and electrochemical detectors (EC) were used in series. Epinephrine was determined and related impurities, i.e., adrenalone, epinephrine sulfonic acid, and norepinephrine, were detected directly in a small portion of the injection solution. Diastereoisomers of the epinephrine enantiomers were prepared by derivatization and determined by LC with a UV detector. The recovery of epinephrine added to epinephrine injection was 100%. The recovery of d-enantiomer from ad, I mixture was 100%. Impurities at levels < 1% were easily detected. The LC method with UV detection is faster and more convenient than the USP XX method. In addition, impurities can be detected in the same portion of sample. The procedure is stability- indicating.

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42

Momi, Stefania, Roberta Caracchini, Emanuela Falcinelli, Stefano Evangelista, and Paolo Gresele. "Stimulation of Platelet Nitric Oxide Production by Nebivolol Prevents Thrombosis." Arteriosclerosis, Thrombosis, and Vascular Biology 34, no. 4 (April 2014): 820–29. http://dx.doi.org/10.1161/atvbaha.114.303290.

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Objective— dl -Nebivolol, a selective β1-adrenergic receptor antagonist, besides its hypotensive activity exerts vasodilatory and platelet inhibitory effects in vitro by a mechanism involving nitric oxide (NO). Our aim was to evaluate whether nebivolol exerts in vivo antithrombotic effects, to unravel the mechanism of this action and to clarify the relative roles of its 2 enantiomers: d - and l -nebivolol. Methods and Results— In wild-type mice, dl -nebivolol, l -nebivolol, and d -nebivolol, but not bisoprolol, reduced mortality consequent to platelet pulmonary thromboembolism induced by the intravenous injection of collagen plus epinephrine (−44%, −45%, −29%, respectively; P <0.05), whereas in eNOS −/− mice only dl -nebivolol and d -nebivolol were effective. dl -Nebivolol, l - and d -nebivolol reduced photochemical damage-induced femoral artery thrombosis in wild-type mice, whereas in eNOS −/− mice only dl -nebivolol and d -nebivolol were active. Moreover, dl -nebivolol and l -nebivolol increased plasma, urinary-, and platelet-derived nitrites and nitrates (NOx), NO degradation products, in wild-type but not in eNOS −/− mice. In vivo platelet activation, assessed by platelet P-selectin expression, was reduced by dl -nebivolol and l - and d -nebivolol in wild-type mice but only by dl -nebivolol and d -nebivolol in eNOS −/− mice. In bone marrow–transplanted, chimeric mice with only blood cells, and not the endothelium, producing NO dl -nebivolol and l -nebivolol maintained their antithrombotic activity, whereas they lose it in chimeras with only endothelium, and not blood cells, producing NO. In vitro, with isolated platelets, dl -nebivolol and l -nebivolol, but not d -nebivolol and bisoprolol, increased platelet cGMP and NOx formation. Treatment with dl -nebivolol and l -nebivolol increased phophorylated eNOS in platelets. Conclusions— Our data show that dl -nebivolol exerts an antithrombotic activity by stimulating the formation of NO by platelets, and that this effect is generated by its l -enantiomer, whereas the d -enantiomer exerts a weak antiplatelet effect because of β−adrenergic receptor–independent stimulation of adenyly cyclase. These results confirm that platelet-derived NO plays a role in thrombosis prevention and it may represent a target of pharmacological intervention.

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Patel, M., I. S. Kayani, W. Templeton, G. W. Mellor, E. W. Thomas, and K. Brocklehurst. "Evaluation of hydrogen-bonding and enantiomeric P2-S2 hydrophobic contacts in dynamic aspects of molecular recognition by papain." Biochemical Journal 287, no. 3 (November 1, 1992): 881–89. http://dx.doi.org/10.1042/bj2870881.

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1. 2-(N′-Acetyl-D-phenylalanyl)hydroxyethyl 2′-pyridyl disulphide (compound IV) (m.p. 59 degrees C; [alpha]D20 -6.6 degrees (c 1.2 in methanol)) was synthesized. 2. The results of a study of the pH-dependence of the second-order rate constant (k) for its reaction with the catalytic-site thiol group (Cys-25) of papain (EC 3.4.22.2) together with analogous kinetic data for the reactions of related time-dependent inhibitors, notably the L-enantiomer of compound (IV) (compound III) and the L- and D-enantiomers of 2-(N′-acetylphenylalanylamino)ethyl 2′-pyridyl disulphide (compounds I and II respectively), were used to assess the contributions of the (P1)-NH ... O = C < (Asp-158) and (P2) > C = O ... H-N-(Gly-66) hydrogen bonds and enantiomeric P2-S2 hydrophobic contacts in two manifestations of dynamic molecular recognition in papain-ligand association: (a) signalling to the catalytic-site region to provide for a (His-159)-IM(+)-H-assisted transition state and (b) the dependence of P2-S2 stereoselectivity on hydrogen-bonding interactions outside the S2 subsite. The analysis involved determination of the reactivities of individual ionization states of the reactions (pH-independent rate constants, k) and associated macroscopic pKa values and difference kinetic specificity energies (delta delta GKS = -RT1n(k1/k2), where k1 is the pH-independent second-order rate constant for reaction with one inhibitor and k2 is the analogous rate constant in the same ionization state for reaction with another inhibitor so that, when the structural change provides that k2 > k1, delta delta GKS is positive. 3. The kinetic data further illuminate the nature of the interdependence of binding interactions in papain first noted by Kowlessur, Topham, Thomas, O'Driscoll, Templeton & Brocklehurst [(1989) Biochem. J. 258, 755-764] in the S2 subsite, S1-S2 intersubsite and catalytic-site regions. Of particular note is the apparent dependence of the binding of the N-Ac-D-Phe moiety on the binding of the leaving group to (His-159)-Im+H and the fact that the resulting rate enhancement is more effective when (P1)-N-H is absent than when it is present. This result revealed by kinetic analysis goes beyond the conclusion suggested by model building that it is possible to make all of the binding contacts in complexes involving the D-enantiomers [(II) and (IV)] as in those involving the L-enantiomers [(I) and (III)].(ABSTRACT TRUNCATED AT 400 WORDS)

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Furman, P. A., J. E. Wilson, J. E. Reardon, and G. R. Painter. "The Effect of Absolute Configuration on the Anti-HIV and Anti-HBV Activity of Nucleoside Analogues." Antiviral Chemistry and Chemotherapy 6, no. 6 (December 1995): 345–55. http://dx.doi.org/10.1177/095632029500600601.

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This review concerns the effect of stereoisomerism on the selective activity of anti-HIV and anti-HBV nucleoside analogues. The synthesis of a number of nucleoside analogues with anti-HIV and anti-HBV activity yields mixtures of 1-β-D and 1-β-L stereoisomers. Anti-HIV and anti-HBV activity is associated primarily with one of the two enantiomers and the more potent activity does not always reside with the 1-β-D configuration characteristic of natural nucleosides. In the case of HIV, the origin of this stereoselectivity appears to be the result of differential metabolism of the analogues and not due to differential inhibition of the target enzyme; the HIV reverse transcriptase. However, mutations at position 184 of the HIV-RT does result in stereoselective inhibition of the enzyme. On the other hand, with HBV, there is also a stereoselective inhibition of the HBV DNA polymerase, where the 5′-triphosphate of the 1-β-L enantiomer is the more potent inhibitor.

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Chen, Ming, Shuanglong Wang, and Xihan Yu. "Correction: Cryptand-imidazolium supported total synthesis of the lasso peptide BI-32169 and its d-enantiomer." Chemical Communications 56, no. 63 (2020): 9040. http://dx.doi.org/10.1039/d0cc90330b.

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46

Karim, Md Rokon Ul, Enjuro Harunari, Amit Raj Sharma, Naoya Oku, Kazuaki Akasaka, Daisuke Urabe, Mada Triandala Sibero, and Yasuhiro Igarashi. "Nocarimidazoles C and D, antimicrobial alkanoylimidazoles from a coral-derived actinomycete Kocuria sp.: application of 1 J C,H coupling constants for the unequivocal determination of substituted imidazoles and stereochemical diversity of anteisoalkyl chains in microbial metabolites." Beilstein Journal of Organic Chemistry 16 (November 5, 2020): 2719–27. http://dx.doi.org/10.3762/bjoc.16.222.

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Chemical investigation of secondary metabolites from a marine-derived actinomycete strain of the genus Kocuria, isolated from a stony coral Mycedium sp., led to the identification of two new alkanoylimidazoles, nocarimidazoles C (1) and D (2) as well as three known congeners, nocarimidazoles A (3) and B (4) and bulbimidazole A (5). Structure analysis of 1 and 2 by NMR and MS revealed that both are 4-alkanoyl-5-aminoimidazoles with a 6-methyloctanoyl or decanoyl chain, respectively. Two possible positions of the amino group on the imidazole rings (C-2 and C-5) posed a challenge in the structure study, which was settled by the measurement of 1 J C,H coupling constants for comparison with those of synthetically prepared model imidazoles. The absolute configurations of the anteisoalkanoyl group present in 1, 4, and 5 were determined by low-temperature HPLC analysis of the degradation products labeled with a chiral anthracene reagent, which revealed that 1 is a mixture of the R- and S-enantiomers with a ratio of 73:27, 4 is the pure (S)-enantiomer, and 5 is the (S)-enantiomer with 98% ee. The present study illustrates the diversity in the stereochemistry of anteiso branching in bacterial metabolites. Compounds 1−4 were moderately antimicrobial against Gram-positive bacteria and fungi, with MIC ranges of 6.25–25 μg/mL.

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Tanaka, Mikiei, Yasuo Mukohata, and Seiji Yuasa. "Utilization of D-amino acids by Halobacterium halobium R1mR." Canadian Journal of Microbiology 35, no. 4 (April 1, 1989): 508–11. http://dx.doi.org/10.1139/m89-078.

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Halobacterium halobium R1mR required L-amino acids such as methionine, leucine, valine, isoleucine, arginine, and lysine for growth. They also grew, with a lag phase of 15 to 20 days, when phenylalanine or tyrosine was omitted from the medium. This represents the first evidence that halophilic bacteria can grow on either D-methionine, D-phenylalanine, D-tyrosine, or D-leucine, each of which was substituted for the opposite enantiomer in the medium.Key words: halobacteria, D-amino acid.

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Arvidsson, Michel, Marja-Liisa Dahl, Olof Beck, Gerd Ackehed, Karin Nordin, and Staffan Rosenborg. "Pharmacokinetics of methylphenidate and ritalinic acid in plasma correlations with exhaled breath and oral fluid in healthy volunteers." European Journal of Clinical Pharmacology 76, no. 2 (November 30, 2019): 229–37. http://dx.doi.org/10.1007/s00228-019-02787-x.

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Abstract Purpose The primary aim of this study was to explore the potential of alternative sampling matrices for methylphenidate by assessing the correlations between dl-threo-methylphenidate and dl-threo-ritalinic acid concentrations in exhaled breath and oral fluid with those in plasma, in repeated samples collected after a single oral dose of methylphenidate. The secondary aim was to study the enantioselective pharmacokinetics of methylphenidate in plasma, with a focus on interindividual variability in the metabolism of methylphenidate to ritalinic acid. Methods Twelve healthy volunteers received a single oral dose of dl-threo-methylphenidate (Ritalin® capsules, 20 mg). Venous blood samples were collected for 24 h, and plasma analyzed for threo-enantiomers of methylphenidate and ritalinic acid with LC-MS/MS. Repeated sampling of exhaled breath, using a particle filter device, and of non-stimulated oral fluid, using a felt pad device, was also performed. Exhaled breath and oral fluid were analyzed with a non-enantioselective LC-MS/MS method for dl-threo-methylphenidate and dl-threo-ritalinic acid. Results In all subjects, d-threo-methylphenidate was detectable in plasma for at least 15 h after the dose with a biphasic profile. l-threo-Methylphenidate was measurable in only five subjects and in most cases in low concentrations. However, one female subject displayed a biphasic concentration-time profile for l-threo-methylphenidate. This subject also had the highest d-threo-methylphenidate AUC (191 ng*h/mL versus 32–119 ng*h/mL in the other subjects). d-threo-Ritalinic acid concentrations were on average 25-fold higher (range 6–126) than the corresponding d-threo-methylphenidate concentrations. Single-time point plasma concentration ratios between d-threo-ritalinic acid and d-threo-methylphenidate 1.5–12 h after dose correlated highly (r = 0.88–0.98) with the d-threo-ritalinic acid AUC/d-threo-methylphenidate AUC ratio. In eleven subjects, dl-threo-methylphenidate in oral fluid mirrored the biphasic profile of methylphenidate (sum of d- and l-threo-enantiomers) in plasma, but the concentrations in oral fluid were on average 1.8 times higher than in plasma. dl-threo-Methylphenidate was detected in exhaled breath in all subjects, but there was no consistent concentration-time pattern. Conclusions In some subjects, the pharmacologically less active l-threo-enantiomer may contribute to the total plasma methylphenidate concentrations. Monitoring methylphenidate concentrations without enantiomeric determination carries the risk of missing such subjects, which might affect how the plasma concentrations of methylphenidate are interpreted and used for clinical decision making. The use of exhaled breath and oral fluid to assess medication adherence to MPH in patients with ADHD warrants further studies.

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Drozdzal, Pawel, Miroslaw Gilski, and Mariusz Jaskolski. "Ultrahigh-resolution centrosymmetric crystal structure of Z-DNA reveals the massive presence of alternate conformations." Acta Crystallographica Section D Structural Biology 72, no. 11 (October 28, 2016): 1203–11. http://dx.doi.org/10.1107/s205979831601679x.

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The self-complementary d(CGCGCG) hexanucleotide was synthesized with both D-2′-deoxyribose (the natural enantiomer) and L-2′-deoxyribose, and the two enantiomers were mixed in racemic (1:1) proportions and crystallized, producing a new crystal form withC2/csymmetry that diffracted X-rays to 0.78 Å resolution. The structure was solved by direct, dual-space and molecular-replacement methods and was refined to anRfactor of 13.86%. The asymmetric unit of the crystal contains one Z-DNA duplex and three Mg2+sites. The crystal structure is comprised of both left-handed (D-form) and right-handed (L-form) Z-DNA duplexes and shows an unexpectedly high degree of structural disorder, which is manifested by the presence of alternate conformations along the DNA backbone chains as well as at four nucleobases (including one base pair) modelled in double conformations. The crystal packing of the presented D/L-DNA–Mg2+structure exhibits novel DNA hydration patterns and an unusual arrangement of the DNA helices in the unit cell. The paper describes the structure in detail, concentrating on the mode of disorder, and compares the crystal packing of the racemic d(CGCGCG)2duplex with those of other homochiral and heterochiral Z-DNA structures.

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TATSUTA, KUNIAKI, KOHJI AKIMOTO, MASAHIKOA NNAKA, YUTAKA OHNO, and MITSUHIROK INOSHITA. "Enantiodivergent total syntheses of (-)-nanaomycin D and its enantiomer, (+)-kalafungin." Journal of Antibiotics 38, no. 5 (1985): 680–82. http://dx.doi.org/10.7164/antibiotics.38.680.

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Journal articles on the topic 'D-enantiomer'

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