- Optimization of the use of a chiral bio-based building block for the manufacture of DHPPA, a key intermediate for propionate herbicides
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An alternative route for the production of (R)-2-(4-hydroxyphenoxy) propionic acid (DHPPA), a key intermediate in herbicide chemistry, is proposed. This route makes use of a chiral building block, initially produced by fermentation. The route has been optimized based on two steps: chlorination and etherification. The chlorination step has a maximum ee of 99% and a yield of 85% after distillation. The etherification step has a yield of 66%. Comparison of the route with the industrial standard shows a significant improvement in terms of green chemistry: waste streams are lowered up to 7-fold and the toxicity of the waste streams is reduced. This journal is the Partner Organisations 2014.
- Fleer, Michel P. M.,Verkuijl, Bastiaan J. V.
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- Roof shape chiral alcohol: auxiliary for asymmetric synthesis of α-halo acid derivatives
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Roof shape chiral enantiopure alcohol, obtained by bio-catalytic separation of isomers, was used as a new auxiliary for asymmetric synthesis of α-halo acid derivatives. Esterification reaction of roof shape chiral enantiopure alcohol and racemic α-halo acids in the presence of DCC, DMAP furnished diastereomers of ester in non-racemic manner. Diastereoselectivity up to 90% was observed, the absolute configuration of newly generated chiral center was established by the single crystal X-ray diffraction analysis.
- Jain, Nilesh,Bedekar, Ashutosh V.
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- Asymmetric reduction of 2-chloroacrylic acid to (S)-2-chloropropionic acid by a novel reductase from Burkholderia sp. WS
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Burkholderia sp. WS has a novel enzyme that catalyzes the asymmetric reduction of 2-chloroacrylic acid to yield (S)-2-chloropropionic acid, which is used as a building block for the synthesis of aryloxyphenoxypropionic acid herbicides. NADPH is required as a co-substrate for this reaction.
- Kurata, Atsushi,Kurihara, Tatsuo,Kamachi, Harumi,Esaki, Nobuyoshi
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- Energetics of the C-Cl bond in CH3CH(Cl)COOH. Enthalpy of formation of (S)-(-)-2-chloropropionic acid and of the 1-carboxyethyl radical
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The energetics of the C-Cl bond in 2-chloropropionic acid was investigated by using a combination of experimental and theoretical methods. The standard molar enthalpy of formation of liquid (S)-(-)-2-chloropropionic acid, at 298.15 K, was determined as ΔfH°m(C3H5O2Cl, l) = - 534.6 ± 1.1) kJ?mol-1, by rotating-bomb combustion calorimetry. The corresponding enthalpy of vaporization, ΔvapH°m (C3H5O2Cl) = (64.9 ± 0.5) kJ?mol-1, was also obtained from vapor pressure versus temperature measurements by the transpiration method, leading to ΔfH°m(C3H5O2Cl, g) = -(469.7 ± 1.2) kJ?mol-1. This value, together with the enthalpy of the isodesmic and isogyric gas-phase reaction CH3CH(X)COOH(g) + C2H5(g) → CH3CHCOOH(g) + C2H5X(g) (X = H, Cl) predicted by density functional theory calculations and other auxiliary data, was used to derive the enthalpy of formation of the gaseous 1-carboxyethyl radical as ΔfH°[CH(CH3)COOH, g] = -(293 ± 3) kJ?mol-1, from which DH°[H-CH(CH3COOH] = 380.7 ± 3.9 kJ?mol-1 and DH°[Cl-CH(CH3)COOH] = 298.0 ± 3.2 kJ?mol-1 were obtained. These values are compared with the corresponding C-H and C-Cl bond dissociation enthalpies in XCH2COOH, XCH3, XC2H5, XCH2-Cl, XCH(CH3)Cl, XCH-CH2, and XC6H5 (X = H, Cl). The order DH°(C-H) 3)COOH] and DH°[X-CH2COOH] (X = H, Cl) indicates that the replacement of a hydrogen of the CH2 group of XCH2COOH by a methyl group leads to a decrease of both the C-H and C-Cl bond dissociation enthalpy. It is finally concluded that the major qualitative trends exhibited by the C-Cl bond dissociation enthalpies for the series of compounds addressed in this work can be predicted based on Pauling's electrostatic-covalent model.
- Lagoa, Ana L.C.,Diogo, Herminio P.,Minas da Piedade, Manuel E.,Amaral, Luisa M.P.F.,Guedes, Rita C.,Costa Cabral, Benedito J.,Kulikov, Dmitry V.,Verevkin, Sergey P.,Siedler, Michael,Epple, Matthias
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- A facile microwave assisted synthesis and structure elucidation of (3R)-3-alkyl-4,1-benzoxazepine-2,5-diones by crystallographic, spectroscopic and DFT studies
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The use of microwave (MW) irradiation in organic synthesis has become increasingly popular within the pharmaceutical and academic arenas because it is a new enabling technology for drug discovery and development. It is a rapid way of synthesis, which involves faster reaction rates and high selectivity to conventional heating method of syntheses. The MW-assisted 7-exo-tet cyclization of N-acylanthranilic acids afforded (3R)-3-alkyl-4,1-benzoxazepines-2,5-diones in very short duration (20 min) with extraordinary high yields in comparison to conventional heating mode of synthesis. The method development, comparative yields of MW-assisted and thermal method of syntheses, crystallographic, spectroscopic and density functional theory (DFT) studies are reported herein. Four novel compounds with chemical formulas C10H9BrClNO3 5m, C19H19NO3 6e, C13H14ClNO3 6h and C12H11Br2NO3 6h were synthesized, validated by 1HNMR, 13CNMR, FT-IR, UVVis, EIMS spectroscopic techniques and confirmed by using single crystal X-ray diffraction (SC-XRD) study. The DFT and TDDFT calculations at B3LYP/6-311 + G(d,p) level of theory were performed for comparative analysis of spectroscopic data, optimized geometries, frontier molecular orbitals (FMOs), natural bond orbital (NBO) analysis and nonlinear optical (NLO) properties of 5m, 6e, 6h and 6o. Overall, experimental findings were supported nicely by corresponding DFT computed results. The NBO analysis confirmed that the presence of non-covalent interactions, hydrogen bonding and hyper- conjugative interactions are pivotal cause for the existence of 5m, 6e, 6h and 6o in the solid-state. NLO analysis showed that 5m, 6e, 6h and 6o have significant NLO properties as compared to prototype standard compound which disclosed their potential for technology related applications.
- Raza, Abdul Rauf,Nisar, Bushra,Khalid, Muhammad,Gondal, Humaira Yasmeen,Khan, Muhammad Usman,de Alcantara Morais, Sara Figueirêdo,Tahir, Muhammad Nawaz,Braga, Ataualpa Albert Carmo
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- Applications of chiral naphthyloxycyclohexanols in deracemization of α-substituted carboxylic acids by dynamic thermodynamic resolution
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Two derivatives of trans-2-naphthyloxycyclohexanol were synthesized, their enantiomers were separated by enzyme mediated kinetic resolution and their absolute configuration was established by synthesizing their diastereomers with esters of known chiral description. Chiral alcohols were then used as chiral auxiliaries for the preparation of esters by coupling with racemic α-halo acids. During the coupling reactions with DCC and a suitable base, an efficient dynamic thermodynamic resolution was observed and the products were isolated in high diastereomeric purity. The effect of several parameters on the reaction was studied and the absolute configuration of a newly created chiral centre was established by single crystal X-ray analysis; the correlation of the structure of chiral auxiliary and diastereoselectivity was investigated. The observed diastereoselectivity was in accordance with the relative energy profile of the products. The chirally pure α-halo acid could be separated from the auxiliary, without any loss of optical purity of both components.
- Khanvilkar, Aditya N.,Samanta, Sudeep G.,Bedekar, Ashutosh V.
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p. 2670 - 2683
(2019/03/12)
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- Synthetic method of high-purity and high-yield L-2-chloropropionic acid
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The invention discloses a synthetic method of L-2-chloropropionic acid. The synthetic method comprises the steps of firstly dissolving L-alanine into hydrochloric acid, introducing nitrosyl chloride and hydrogen chloride gas for reaction, after the raw materials are converted, filtering, continuing to stir for 1-2 hours, and an alkaline reagent for neutralization, extracting by virtue of an organic solvent, combining organic phases, drying by virtue of anhydrous calcium chloride, filtering, and carrying out rectification, so as to obtain a product, namely L-2-chloropropionic acid. The method has the advantages that the operation is simple, and the emission of wastewater is reduced; and by taking nitrosyl chloride with relatively high activity as a diazotization regent, aliphatic amino canbe rapidly converted into chlorine, so that the raw material conversation rate and the yield are greatly increased, the yield can reach 90% or above, an original configuration is not reversed in the reaction process, and the optical purity ee value can reach 99.1%.
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Paragraph 0021; 0023; 0025; 0027; 0029
(2018/04/26)
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- Synthesis method of pesticide intermediate (S)-(-)-2-chloropropionic acid
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The invention relates to a synthesis method of pesticide intermediate (S)-(-)-2-chloropropionic acid. The method comprises the step of enabling (S)-2-chloropropionic acid, used as a starting raw material, and sodium nitrite to be subjected to a diazo-reaction in presence of a catalyst and lewis acid so as to obtain the (S)-(-)-2-chloropropionic acid product. The synthesis method improves the yield, content and optical purity of the product, reduces the production cost, and improves the product quality; the optical purity of the obtained (S)-(-)-2-chloropropionic acid is e.e. 99% or above, andthe reaction yield is 85% or above; the synthesis method is short in reaction route and simple in aftertreatment, and has a great guiding significance for process amplification and production.
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Paragraph 0033-0050
(2020/05/19)
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- Di(1-naphthyl) methanol ester of carboxylic acids for absolute stereochemical determination
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The absolute stereochemistry of chiral carboxylic acids is determined as a di(1-naphthyl)methanol ester derivative. Computational scoring of conformations favoring either P or M helicity of the naphthyl groups, capable of exciton-coupled circular dichroic coupling, leads to a predicted stereochemistry for the derivatized carboxylic acids.
- Zhang, Jun,Sheng, Wei,Gholami, Hadi,Nehira, Tatsuo,Borhan, Babak
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supporting information
p. 141 - 146
(2017/11/13)
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- Novel method for preparing hexamethyl propyleneamine oxime and intermediate thereof
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The present invention relates to a novel synthesis method of hexamethyl propyleneamine oxime (HMPAO) and an intermediate thereof, wherein the method comprises a step of conducting a reaction of a compound of chemical formula 4a with methyl magnesium halide (CH_3MgX) or methyl lithium (CH_3Li) to synthesize a compound represented by chemical formula 3a. Unlike conventional methods having unsatisfactory separation efficiency, or complicated synthesis processes and low yield, the synthesis method of the present invention can produce l-HMPAO, d-HMPAO and d,l-HMPAO in a high yield without producing meso-HMPAO.COPYRIGHT KIPO 2018
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Paragraph 0090
(2018/05/03)
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- Chiral Pool-Based Synthesis of Naphtho-Fused Isocoumarins
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A variety of chiral derivatives of benzo[d]naphtho[1,2-b]pyran-6-one were prepared in a single step by Et3N-mediated condensation of homophthalic anhydride with different derivatives of (S)-amino acid chlorides at -5 °C by employing a chiral pool methodology. Chirality 27:951-957, 2015.
- Raza, Abdul Rauf,Saddiqa, Aisha,?akmak, Osman
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p. 951 - 957
(2015/11/16)
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- Synthesis of orthogonally protected muramic acid building blocks for solid phase peptide synthesis
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Muramic acid is found in many peptide natural products containing oligo(poly)saccharide moieties. Taking into consideration that the Fmoc methodology is routinely used for solid-phase peptide synthesis, preparation of orthogonally protected muramic acid building blocks for total solid-phase synthesis of these natural products is of particular practical importance. Herein a simple and efficient synthesis of benzyl 2-amino-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-N-9-fluorenylmethyloxycarbonyl-α-D-glucopyranoside (6) from N-acetylglucosamine (1) is described. Important improvements over previous synthetic approaches to glucopyranosides 2 (benzyl 2-acetamido-2-deoxy-α-D-glucopyranoside) and 3 (benzyl 2-acetamido-4,6-O-benzylidene-2-deoxy-α-D-glucopyranoside), key building blocks in preparation of 6, include synthesis simplification and efficient isolation and purification. Optically pure (S)-2-chloropropionic acid 7 was prepared and introduced to the positon 3-O of sugar moiety to give compound 4 (benzyl 2-acetamido-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-α-D-glucopyranoside) with the (R)-configuration of the lactyl side-chain in excellent overall yield and optical purity. Deacetylation of amino group gave compound 5 (benzyl 2-amino-4,6-O-benzylidene-3-O-[(R)-1-carboxyethyl]-2-deoxy-α- D-glucopyranoside) suitable for incorporation of the Fmoc protecting group to give protected muramic acid derivative 6, a useful building block in peptide synthesis.
- Vlahoviek-Kahlina, Kristina,Jakas, Andreja
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p. 151 - 157
(2015/08/06)
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- Chiron based synthesis of isocoumarins: Reactivity of α-substituted carboxylic acids
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The asymmetric synthesis of a novel (S)-isocoumarin has been attempted in a single step by the coupling of homophthalic acid with (S)-N-protected amino acids and α-chloroacids at high temperature by exploiting a chiral pool methodology. The coupling of homophthalic acid with N-protected (S)-amino acids gave exclusion of the carboxyl/alkyl group. However, coupling of homophthalic acid with α-chloroacids afforded asymmetric isocoumarins in high yield.
- Saddiqa, Aisha,Raza, Abdul R.,Black, David Stc.,Kumar, Naresh
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p. 736 - 743
(2014/06/09)
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- Conformational preference in bis(porphyrin) tweezer complexes: A versatile chirality sensor for α-chiral carboxylic acids
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Metallated porphyrin tweezers have demonstrated a remarkable ability to function as reporters of absolute stereochemistry for a number of different classes of organic molecules. Flexibility in binding, however, can result in an ensemble of different Exciton Coupled Circular Dichroism (ECCD) active conformations that could lead to variable results. Linker flexibility was found to be a key determinant of binding conformation. Experimental results indicate that a balance between linker flexibility and rigidity could yield an optimum porphyrin tweezer that stabilizes a common conformation for all bound chiral guests. This leads to a more simplified approach to absolute stereochemical determination of asymmetry for small organic molecules. This was demonstrated by the use of a C3-linked zincated porphyrin tweezer that yields a common conformational preference for a variety of α-chiral carboxylic acids derivatized with a diamine carrier. Copyright
- Tanasova, Marina,Borhan, Babak
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supporting information; experimental part
p. 3261 - 3269
(2012/07/01)
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- A substrate-driven approach to determine reactivities of α,β-unsaturated carboxylic esters towards asymmetric bioreduction
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The degree of C=C bond activation in the asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases was studied, and general recommendations to render these "borderline-substrates" more reactive towards enzymatic reduction are proposed. The concept of "supported substrate activation" was developed. In general, an additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates, and α-cyano groups showed little effect. The alcohol moiety of the ester functionality was found to have a strong influence on the reaction rate. Overall, activities were determined by both steric and electronic effects. Biotransformation: The asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases could be tuned by varying the degree of C=C bond activation (see scheme). An additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates. Copyright
- Tasnádi, Gábor,Winkler, Christoph K.,Clay, Dorina,Sultana, Nargis,Fabian, Walter M. F.,Hall, Mélanie,Ditrich, Klaus,Faber, Kurt
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supporting information; experimental part
p. 10362 - 10367
(2012/10/08)
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- An unusual conformation of α-haloamides due to cooperative binding with zincated porphyrins
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CD and NMR spectroscopic evidence of cooperative binding between an α-halogen atom and a carboxamide group with a zinc porphyrin leads to an unprecedented conformation for the determination of the absolute stereochemistry of α-haloamides (α-halocarboxylic acids derivatized with 1,4-phenylenediamine) through the use of exciton-coupled circular dichroism (ECCD). With the use of chiral lactams, whose rotomeric contributions are minimized, both ECCD and NMR spectroscopy demonstrate that the porphyrin favors binding to the side of the sterically more demanding halogen atom as compared to the smaller hydrogen atom. In all, the data is strongly suggestive of an unusual conformation not observed before for α-chiral amides. A mnemonic for determining the absolute stereochemistry of α-halogenated carboxylic acids is provided.
- Tanasova, Marina,Yang, Qifei,Olmsted, Courtney C.,Vasileiou, Chrysoula,Li, Xiaoyong,Anyika, Mercy,Borhan, Babak
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supporting information; experimental part
p. 4242 - 4253
(2011/02/25)
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- Superparamagnetic nanoparticle-supported enzymatic resolution of racemic carboxylates
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Candida rugosa lipase immobilized on maghemite nanoparticles demonstrated high stereoselectivity in kinetic resolution of racemic carboxylates and improved long-term stability over its parent free enzyme, allowing the supported enzyme to be repeatedly used for a series of chiral resolution reactions. The Royal Society of Chemistry 2005.
- Gardimalla, Hari M. R.,Mandal, Deendayal,Stevens, Philip D.,Yen, Max,Gao, Yong
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p. 4432 - 4434
(2007/10/03)
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- Direct Organocatalytic Asymmetric α-Chlorination of Aldehydes
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The direct organocatalytic enantioselective α-chlorination of aldehydes has been developed. The reaction proceeds for a series of different aldehydes with NCS as the chlorine source using easily available catalysts such as L-proline amide and (2R,5R)-diphenylpyrrolidine. The α-chloro aldehydes are obtained in up to 99% yield and up to 95% ee. The synthetic utility of the enantioselective α-chlorination of aldehydes is demonstrated by transformation of the α-chloro aldehydes to the corresponding α-chloro alcohols (>90% yield) by standard reduction and further transformation to both a terminal epoxide and amino alcohol, both obtained without loss of optical purity. Oxidation of the α-chloro aldehydes followed by esterification gave optically active α-chloro esters without loss of optical purity. It is demonstrated that these optically active α-chloro esters can be converted into nonproteinogenic amino acids in overall high yields, maintaining the enantiomeric excess obtained in the catalytic enantioselective α-chlorination step. Copyright
- Halland, Nis,Braunton, Alan,Bachmann, Stephan,Marigo, Mauro,Jorgensen, Karl Anker
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p. 4790 - 4791
(2007/10/03)
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- Mapping the substrate selectivity of new hydrolases using colorimetric screening: Lipases from Bacillus thermocatenulatus and Ophiostoma piliferum, esterases from Pseudomonas fluorescens and Streptomyces diastatochromogenes
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Recent advances in biochemistry and molecular biology have simplified the discovery and preparation of new hydrolases. Although these hydrolases might solve problems in organic synthesis, measuring their selectivity, especially enantioselectivity, remains tedious and time consuming. Recently, we developed a colorimetric screening method to measure the enantioselectivity of hydrolases. Here we apply this rapid screening method to map the substrate selectivity of four new hydrolases: lipases from the thermophilic Bacillus thermocatenulatus (DSM 730, BTL2) and a filamentous fungus Ophiostoma piliferum (NRRL 18917, OPL) and esterases from two bacteria, Pseudomonas fluorescens (SIK-W1, esterase I, PFE) and Streptomyces diastatochromogenes (Tue 20, SDE). We screened a general library of 29 substrates and a chiral library of 23 pairs of enantiomers. All four hydrolases catalysed the hydrolysis of unnatural substrates, but the two lipases accepted a broader range of substrates than the two esterases. As expected, the two lipases favoured more hydrophobic substrates, while the two esterases showed a preference for smaller substrates. Several moderately enantioselective reactions were identified for the solketal esters: BTL2, butyrate, E = 7.9 (R); octanoate, E = 4.9 (R) and 3-bromo-2-methyl propionate methyl esters, PFE, E = 12 (S); SDE, E = 5.6 (S). OPL showed low enantioselectivity toward all substrates tested. The current colorimetric screen could not measure the selectivity for several slow-reacting substrates. Traditional screening identified high enantioselectivity of BTL2 and PFE toward one of these slow substrates, 1-phenylethyl acetate (E>50).
- Liu, Andrew Man Fai,Somers, Neil A.,Kazlauskas, Romas J.,Brush, Terry S.,Zocher, Frank,Enzelberger, Markus M.,Bornscheuer, Uwe T.,Horsman, Geoff P.,Mezzetti, Alessandra,Schmidt-Dannert, Claudia,Schmid, Rolf D.
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p. 545 - 556
(2007/10/03)
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- Design, construction and properties of peptide N-terminal cap templates devised to initiate α-helices. Part 1. Caps derived from N-(4-chlorobutyryl)-(2S)-Pro-(2S)-Pro-(2S)-Ala-OMe and N-[(2S)-2-chloropropionyl]-(2S)-Pro-(2S)-Pro-(2S,4S)-4-hydroxyPro-OMe
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The structural features required of N-terminal helix caps which might display high α-helix-forming propensities (Zimm-Bragg σ-values close to unity) were considered and two systems were identified as initial candidates for synthesis and evaluation. The first system was an eleven-membered cyclic all-trans triamide derived from N-(4-chlorobutyryl)-(2S)-Pro-(2S)-Pro-(2S)-Ala-OMe in which it was intended to remove the only amide NH proton to generate a better nucleophile, and then ring-close by displacing the 4-halogen atom as halide. The precursor was prepared in moderate overall yield and displayed conformational isomerism in chloroform solution. Some of the conformers appeared to contain one or more cis amide bonds. No suitable conditions could be found to effect macrocyclisation. The second system was a twelve-membered cyclic all-trans triamide derived from N-[(2S)-2-chloropionyl]-(2S)-Pro-(2S)-Pro-(2S,4S)-4-hydroxyPro-OMe in which it was intended to generate an alkoxide anion and then ring-close by displacing halide ion from the 2-chloropropionyl moiety. The precursor was prepared in moderate overall yield and populated one all-trans rotameric form in chloroform solution. This system also failed to macrocyclise under a variety of conditions. The major reason for the lack of reactivity in each system was analysed and appeared to be the generation of large molecular dipoles in the transition state for the cyclisation, originating from the requirement for the alignment of the carboxamide carbonyl groups. Useful modifications to the systems described here that were designed to overcome or minimise the effect of the dipole in destabilising the required conformation for helix cap generation are presented in the following two articles.
- Lewis, Arwel,Ryan, Martin D.,Gani, David
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p. 3767 - 3775
(2007/10/03)
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- (R)- and (S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone as chiral auxiliaries in the enantioselective preparation of α-aryloxypropanoic acid herbicides and α-chlorocarboxylic acids
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rac-α-Chlorocarboxylic acids, rac-9a-e, were formally deracemized by reaction of the corresponding acyl chlorides with the chiral auxiliaries (R)- and (S)-3-hydroxy-4,4-dimethyl-1-phenyl-2-pyrrolidinone, (R)- and (S)-4, followed by mild alkaline hydrolysis. The highest o.p. (99%) was obtained in the case of (S)-α-chloropropanoic acid, a known precursor for the synthesis of (R)-α-aryloxypropanoic acid herbicides such as dichlorprop-P, (R)-3a, or mecoprop-P, (R)-3b, which, together with their enantiomers, were also obtained in moderate e.e.s by dynamic kinetic resolution from (αRS,3S)-4,4- dimethyl-2-oxo-l-phenylpyrrolidin-3-yl α-bromopropanoate, (αRS,3S)-6, by reaction with the corresponding phenoxide followed by mild acid hydrolysis.
- Camps, Pelayo,Perez, Francesc,Soldevilla, Nuria
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p. 2065 - 2079
(2007/10/03)
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- Empirical rules for the enantiopreference of lipase from Aspergillus niger toward secondary alcohols and carboxylic acids, especially α-amino acids
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Lipase from Aspergillus niger (ANL, Amano lipase AP) catalyzes enantioselective hydrolysis and acylation reactions. To aid in the design of new applications of this lipase, we propose two empirical rules that predict which enantiomer reacts faster. For secondary alcohols, a rule proposed previously for other lipases also works for ANL, but with lower reliability (77%, 37 of 48 examples). For carboxylic acids, we examined both crude and partially-purified ANL because commercial ANL contains contaminating hydrolases. Partial purification removed a contaminating amidase and increased the enantioselectivity of ANL toward many α-amino acids, including cyclic amino acids. Unlike other lipases, ANL readily accepts positively-charged substrates and shows the highest enantioselectivity towards α-amino acids. Although a rule based on the sizes of the substituents could not predict the fast-reacting enantiomer, a rule limited to α-amino acids did predict the fast-reacting enantiomer. We estimate that the charged α-amino group contributes a factor of 40-100 (ΔΔ≠ = 2.2-2.7 kcal/mol) to the enantioselectivity of ANL towards carboxylic acids.
- Janes, Lana E.,Kazlauskas, Romas J.
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p. 3719 - 3733
(2007/10/03)
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- Asymmetric Synthesis of 2-Chloro- and 2-Bromo-alkanoic acids by Halogenation of α-D-Glucofuranose-Derived Silyl Ketene Acetals.
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Optically active (S)-2-bromo- and 2-chloro-alkanoic acids 6 and 7 have been obtained via the diastereoselective halogenation of chiral silyl ketene acetals 3a-f, and subsequent saponification of the resulting crude esters.Examples characterized by e.e. values up to 95percent are reported.The diastereoface selectivity is independent of the silyl ketene acetal E/Z configuration.
- Angibaud, P.,Chaumette, J. L.,Desmurs, J. R.,Duhamel, L.,Ple, G.,et al.
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p. 1919 - 1932
(2007/10/03)
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- A Highly Efficient Synthesis of the Anthelmintic Cyclooctadepsipeptide PF1022A
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The potent anthelmintic cyclooctadepsipeptide PF1022A was synthesized by a series of fragment condensations starting from the known (S)-2-chloropropanoic acid and (S)-2-chloro-3-phenylpropanoic acid in eleven steps with a total yield of 13percent.Noteworthy is the excellent yield of the BOP-Cl mediated lactamization reaction of the linear precursor 17 leading to the 24-membered macrocycle.
- Scherkenbeck, Juergen,Plant, Andrew,Harder, Achim,Mencke, Norbert
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p. 8459 - 8470
(2007/10/02)
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- Molecular properties of the WB4101 enantiomers and of its chiral methyl derivatives for α1-adrenoceptor recognition
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The optical isomers of the well known α1-antagonist WB4101 and of its derivatives with a methyl group in the oxyethyl moiety were prepared for the evaluation of their α-adrenoceptors binding affinity. By means of a detailed computational analysis, the present work shows that the introduction of a methyl group affects the behaviour of WB4101 in different ways. A limitation of the conformational freedom in certain regions of the torsional subspace of the potential energy function, differences in the reactivity of the protonated species towards a model proton acceptor and the quality of the superposition with the rigid template for α1 antagonists, corynanthine, are examined and discussed in order to select a candidate bioactive form and possible features which act as modulators of the recognition process at the α1-adrenoceptors.
- Villa,Valoti,Villa,Pallavicini,Ferri,Iuliano,Brunello
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p. 587 - 606
(2007/10/02)
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- Process of producing optically active propionic acid ester derivatives
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Processes for producing optically active ester derivatives are disclosed. According to the present invention an optically active aryloxyphenoxy propionate derivative is produced by reacting a chlorinated heterocyclic aromatic compound with (2R)-2-(4-hydroxyphenoxy)propionic acid tetrahydrofurfuryl ester in an anhydrous solvent in the presence of a base. According to the present invention, an optically active propionate derivative of the formula [I] STR1 (wherein R represents hydrogen or 3-chloro-5-trifluoromethyl-2-pyridyl group) is produced by reacting a corresponding optically active methyl propionate derivative with tetrahydrofurfuryl alcohol, or by reacting a corresponding optically active propionic acid derivative with tetrahydrofurfuryl alcohol, or by reacting (2S)-tetrahydrofurfuryl 2-chloropropionate with a corresponding phenol derivative in specific conditions.
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- Liquid crystal compounds having chiral ester head groups
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Liquid crystal compounds which show a ferroelectric phase and which exhibit high spontaneous polarization values and smectic behavior over a range of temperatures have the formula STR1 wherein R1 is alkyl of from 1 to 16 carbon atoms; alkoxy; haloalkyl; alkoxyalkyl, wherein the alkoxy substituent thereof comprises a chain of carbon atoms including one or more oxygen ether atoms; or alkoxyalkoxy, wherein the alkoxy substituent thereof comprises a chain of carbon atoms including one or more oxygen ether atoms; R2 is alkyl of from 1 to 4 carbon atoms; each of R3 and R4 is alkylene; n is an integer 1 or 2; and W is alkyl of from 1 to 12 carbon atoms or fluoroalkyl of the formula STR2 wherein each of X, Y and Z is hydrogen or fluorine, m is zero or an integer from 1 to 6, and at least one of X, Y and Z is fluorine when m is zero.
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- Synthesis and study of new α-haloacid ferroelectric liquid crystal derivatives. MM2 approach to the molecular structure-ferroelectric activity relationship
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In order to understand the structural factors that influence ferroelectric properties, three new series (F, Cl, and Br) of chiral naphthalene-ring derived compounds were synthesized, and their ferroelectric properties [spontaneous polarization (Ps) and response time (τ)] were evaluated in the pure compound. The chiral tails are α-halo acids derived from L-α-amino acids: L-α-alanine (1), L-leucine (2), L-isoleucine (3), and L-valine (4), with a fluorine, chlorine, or bromine atom in the chiral center. The highest Ps values were obtained for compounds containing a fluorine or chlorine atom in their asymmetric center and with chiral tail derived from L-isoleucine (3) (F-3, 102 nC/cm2; Cl-3, 100 nC/cm2). The steric requirements of the halogen atom and the bulky alkyl group in the asymmetric center determine the most stable conformations of these chiral tails, which have been studied by molecular mechanic empirical calculations, MM2. MM2 calculations prove to be a successful tool for understanding how the structure of the lateral chiral tail affects molecular arrangement and, as a consequence, the ferroelectric properties of the materials.
- Sierra,Serrano,Ros,Ezcurra,Zubía
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p. 7645 - 7651
(2007/10/02)
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- ENZYMATIC RECOGNITION OF DIASTEREOMERIC ESTERS
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Aiming to improve the enantioselectivity of enzymatic resolution of esters, lipase catalyzed hydrolysis of (D)- and (L)-2-chloropropanoates of four racemic alcohols and transesterification of ethyl (DL)-2-chloropropanoate with optically pure alcohols was investigated.Thus, (rac)-endo-2-norbornyl (L)-2-chloropropanoate was hydrolized by lipase P about 5 times more selectively than its corresponding (D)-counterpart and optically pure (1R,2S,5R)-menthol was obtained by transesterification of its racemate with ethyl (D)-2-chloropropanoate using Candida cylindracea (CC)lipase.From the results obtained it seems obvious that lipases CC and P mainly can recognize the chirality of an alcohol moiety rather than that of an acid
- Rabiller, C. G.,Koenigsberger, .,Faber, K.,Griengl, H.
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p. 4231 - 4240
(2007/10/02)
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- Specific esterase activity of subtilisin toward esters of α-haloacids
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Esters of α-haloacids are specific substrates for subtilisin which catalyses their hydrolysis in aqueous media. The same esters undergo transesterifications in organic solvents in the presence of subtilisin immobilized on an alumina-phosphate complex.
- Pugniere,Juan, C. San,Previero
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p. 4883 - 4886
(2007/10/02)
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- STEREOCONTROLLED SYNTHESIS OF D-α-HYDROXY CARBOXYLIC ACIDS FROM L-AMINO ACIDS
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Optically active D-α-hydroxy carboxylic acids are obtained from L-amino acids via L-α-halocarboxylic acids and their stereoselective reaction with cesium p-nitrobenzoate.
- Kunz, Horst,Lerchen, Hans-Georg
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p. 1873 - 1876
(2007/10/02)
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- The Determination of Small Amounts of Enantiomeric Impurities in α-Halo Carboxylic Acids
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The accurate determination of the enantiomeric composition of α-halo carboxylic acids is reported.Such data are of importance in the synthesis of chiral compounds and in mechanistic studies involving the title compounds.
- Watabe, K.,Chang, S.-C.,Gil-Av, E.,Koppenhoefer, B.
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p. 225 - 228
(2007/10/02)
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- STEREOSELEKTIVE SYNTHESE VON D-α-HYDROXYCARBONSAEUREN BZW. D-α-HYDROXYCARBONSAEUREN ENTHALTENDEN DEPSIPEPTIDEN AUS L-AMINOSAEUREN
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Depsipeptides containing D-α-hydroxy carboxylic acids are efficiently synthesized by the reactions of L-α-halo-carboxylic acid esters (obtained from L-amino acids) with caesium salts of N-protected amino acids.
- Lerchen, Hans-Georg,Kunz, Horst
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p. 5257 - 5260
(2007/10/02)
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- Resolution of Racemic Mixtures via Lipase Catalysis in Organic Solvents
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Yeast lipase and porcine pancreatic lipase have been found to vigorously function in nearly anhydrous organic solvents and catalyze the reactions of esterification and transesterification, respectively, in highly stereoselective manner.With use of these enzymatic processes, a number of optically active alcohols, carboxylic acids, and their esters have been prepared on a gram scale.
- Kirchner, Gerald,Scollar, Mark P.,Klibanov, Alexander M.
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p. 7072 - 7076
(2007/10/02)
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- Results of Process Research. I. Synthesis of O-propionyl>-acetone oxime
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Efficient and simple procedures for the preparation of O--propionyl>-oxime derivatives 7b-e have been developed.The alkylation of 4-phenol (11) with 7d, the final step of a technical synthesis of 1, has been studied in detail.
- Imfeld, Marquard,Suchy, Milos,Vogt, Peter,Lukac, Teodor,Schlageter, Markus,Widmer, Erich
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p. 1233 - 1241
(2007/10/02)
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- Preparation of Sephadex Derivatives with Optically Active Groups and Column-chromatographic Application to the Resolution of Some Cobalt(III) Complexes
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Optically active cation-exchangers were newly prepared as Sephadex derivatives derived from L-alanine, L-valine, L-aspartic acid, and L-threonine.They were applied to the column-chromatographic resolution of some cobalt(III) complexes, partial resolution being attained.
- Fujita, Miho,Sakano, Masanobu,Yoshikawa, Yuzo,Yamatera, Hideo
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p. 3211 - 3212
(2007/10/02)
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