Tetrahedron Asymmetry

Efficient resolution of profen ethyl ester racemates by engineered Yarrowia lipolytica Lip2p lipase ()
Publication date: Available online 23 February 2017 Source:Tetrahedron: Asymmetry Author(s): Doriane Gérard, Marc Guéroult, Leticia Casas-Godoy, Jean-Stéphane Condoret, Isabelle André, Alain Marty, Sophie Duquesne Enzyme-catalyzed enantiomer discrimination is still a great challenge for the development of industrial pharmaceutical processes. For the resolution of ibuprofen, naproxen and ketoprofen racemates, three major anti-inflammatory drugs, only lipases from Candida rugosa present a high selectivity if solvent and surfactant use is discarded. However, their catalytic activities are too low. In the present work, we demonstrate that the lipase Lip2p from the yeast Yarrowia lipolytica has a higher catalytic activity than C. rugosa lipases to hydrolyze the ethyl esters of ibuprofen, naproxen and ketoprofen, but its selectivity is not sufficient [E =52 (S); 11 (S) and 1.5 (R) respectively]. The enantioselectivity was further improved by site-directed mutagenesis, targeted at the substrate binding site and guided by molecular modelling studies. By investigating the binding modes of the (R)- and (S)-enantiomers in the active site, two amino acid residues located in the hydrophobic substrate binding site of the lipase, namely residues 232 and 235, were identified as crucial for enantiomer discrimination and enzyme activity. The (S) enantioselectivity of Lip2p towards ethyl ibuprofen esters was rendered infinite (E ≫300) by replacing V232 by an A or C residue. Substitution of V235 by C, M, S, or T amino acids led to a great increase in the (S)-enantioselectivity (E ≫300) towards naproxen ethyl ester. Finally, the variant V232F enabled the efficient kinetic resolution of ethyl ketoprofen ester enantiomers [(R)-enantiopreference; E ≫300]. In addition to the increase in selectivity, a remarkable increase in velocity by 2.6, 2.7 and 2.5times, respectively, was found for ibuprofen, naproxen and ketoprofen ethyl esters. Graphical abstract image
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Synthesis of p-coumaroylquinic acids and analysis of their interconversion ()
Publication date: Available online 23 February 2017 Source:Tetrahedron: Asymmetry Author(s): Anggy Lusanna Gutiérrez Ortiz, Federico Berti, Luciano Navarini, Angelo Monteiro, Marina Resmini, Cristina Forzato The synthesis of four isomers of p-coumaroylquinic acids was performed by esterification of p-acetylcoumaroylchloride with a suitably protected (−)-quinic acid. All isomers have been characterized by means of NMR spectroscopy and circular dichroism. Acyl migration was observed in the synthesis of 3-O-p-coumaroylquinic acid and 4-O-p-coumaroylquinic acid. Calculations on the most stable conformations of all isomers have also been performed to explain the acyl migration observed during the synthesis procedure. Graphical abstract image
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Silver-catalyzed diastereo- and enantioselective Michael additions of 2-oxazoline- and 2-thiazoline-4-carboxylate to nitroalkenes ()
Publication date: Available online 23 February 2017 Source:Tetrahedron: Asymmetry Author(s): Akihiro Koizumi, Yukiko Matsuda, Ryosuke Haraguchi, Shin-ichi Fukuzawa The silver/ThioClickFerrophos (a chiral ferrocenyl P,S-ligand)-catalyzed Michael additions of 2-oxazoline- and thiazoline-4-carboxylate to nitroalkenes were highly anti-selective and enantioselective and produced the corresponding adducts in high yields. Graphical abstract image
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Chiral terpene auxiliaries IV: new monoterpene PHOX ligands and their application in the catalytic asymmetric transfer hydrogenation of ketones ()
Publication date: Available online 23 February 2017 Source:Tetrahedron: Asymmetry Author(s): Anna Kmieciak, Marek P. Krzemiński New PHOX ligands, derived in three steps from (1R,2S,3R,5R)-3-amino-apopinan-2-ol 1 and (1R,2R,3S,5R)-3-amino-pinan-2-ol 2 were applied as chiral ligands for the formation of ruthenium catalysts. The catalysts were used in asymmetric transfer hydrogenations of prochiral ketones producing the corresponding alcohols in moderate to high yields and enantioselectivity. Graphical abstract image
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Editorial board ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
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Graphical contents list ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
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Contributors to this issue ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
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The role of hydrazide compounds in asymmetric synthesis ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Ghodsi Mohammadi Ziarani, Vaezeh Fathi Vavsari Asymmetric synthesis is one of the important topics in organic synthesis. Hydrazide compounds are valuable substrates in the fields of both chemical reactions and medicinal chemistry due to their chemical reactivity and biological activities, respectively. In this review, the role of hydrazides as substrates and/or chiral catalysts are investigated in the asymmetric organic reactions to gain chiral products. Graphical abstract image
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Stereoselective synthesis of modified cysteines ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Jaime Gracia-Vitoria, Iñaki Osante, Carlos Cativiela This review provides an overview of the literature concerning the stereoselective synthesis of a large group of modified cysteines. The different synthetic approaches are classified according to the bonds formed to build the cysteine backbone skeleton. Graphical abstract image
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First total synthesis of the highly potent antitumor lactones 8-chlorogoniodiol and parvistone A: Exploiting a bioinspired late-stage epoxide ring-opening ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Perla Ramesh, Yarram Narasimha Reddy, Thatikonda Narendar Reddy, Navuluri Srinivasu The first protecting group-free total syntheses of the highly potent antitumor chlorinated styryllactone secondary metabolites 8-chlorogoniodiol, parvistone A, and one analogue 8-epi-parvistone A, have been accomplished from commercially available trans-cinnamaldehyde in five steps with high overall yields. The chlorine-bearing stereogenic center of these silent secondary metabolites was introduced via a bioinspired late-stage regioselective epoxide ring-opening strategy. Maruoka asymmetric allylation, acrylation, ring-closing metathesis and asymmetric epoxidation, greatly facilitate the synthesis of the key intermediates goniothalamin oxide and (6S,7S,8S)-isogoniothalamin oxide. Graphical abstract image
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Assignment of the absolute configuration of hydroxy acids using 1H NMR spectroscopy: a simple and rapid approach ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Sandeep Kumar Mishra, N. Suryaprakash A simple, rapid and highly effective protocol for assigning the absolute configuration of various chiral α-hydroxy acids and their derivatives has been established by involving the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and 2-formylphenylboronic acid with (S)-[1,1-binaphthalene]-2,2-diamine as chiral derivatizing agents. The absence of aliphatic peaks from the derivatizing agent together with the large chemical shift separation between the discriminated diastereomer peaks, with a systematic change in the direction of the displacement of peaks for an enantiomer in a particular diastereomer complex, allows the unambiguous assignment of absolute configuration. Graphical abstract image
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Highly enantioselective Biginelli reactions using methanopyroline/thiourea – based dual organocatalyst systems: asymmetric synthesis of 4-substituted unsaturated aryl dihydropyrimidines ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Han Yu, Peng Xu, Huihong He, Jun Zhu, Hualin Lin, Sheng Han A series of novel chiral 3,4-dihydropyrimidin-2-(1H)-ones and -thiones (DHPMs) was developed via asymmetric Biginelli reactions catalyzed by a methanopyroline/thiourea – based dual organocatalyst system, providing excellent yield (90–96%) and high enantioselectivities (92–99% ee). Furthermore, novel epoxides with three stereogenic centers are disclosed, which might have application in the field of drugs and pharmaceuticals. Graphical abstract image
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Convenient synthesis of memantine analogues containing a chiral cyclopropane skeleton as a sigma-1 receptor agonist ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Tetsuya Ezawa, Yuya Kawashima, Takuya Noguchi, Seunghee Jung, Nobuyuki Imai We have achieved a convenient enantioselective synthesis of memantine analogues containing a chiral cyclopropane skeleton as a sigma-1 receptor agonist in 19–40% overall chemical yields from the corresponding 2-arylbut-2-ene-1,4-diols with moderate to excellent asymmetric yields via regioselective acetylation using porcine pancreas lipase, catalytic enantioselective Simmons-Smith reactions, and amidation in aqueous organic solvent. This synthetic route is more efficient and less expensive than conventional methods. Graphical abstract image
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Enantioselective chlorinative aldol reaction of α-substituted acroleins catalyzed by chiral phosphine oxides ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Shunsuke Kotani, Takuya Hanamure, Hirono Nozaki, Masaharu Sugiura, Makoto Nakajima The enantioselective chlorinative aldol reaction of α-substituted acroleins with aldehydes catalyzed by chiral phosphine oxides is described. A hypervalent silicon complex-derived chloride adds to the α-substituted acroleins to form the corresponding silyl enol ethers in situ, which subsequently reacts with aldehydes to produce the α-chloromethyl aldol adducts bearing a quaternary stereogenic center in good yields and stereoselectivities. When activated by a phosphine oxide catalyst, trichlorosilyl triflate acts as an effective promoter for the chlorinative aldol reaction as well as the chloride source; this discovery enabled the enantioselective chlorinative aldol reaction of α-substituted acroleins. Graphical abstract image
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Total syntheses of 9-epoxyfalcarindiol and its diastereomer ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Yun Zhou, Yanli Huang, Shuoning Li, Pengfei Yang, Jiangchun Zhong, Jingwei Yin, Kaijie Ji, Yanqing Yang, Ning Ye, Lifeng Wang, Mingan Wang, Min Wang, Qinghua Bian The first total syntheses of 9-epoxyfalcarindiol 1a and its diastereomer 1b have been achieved. Central to our approach were the Zn-cyclopropane-based amino alcohol catalyzed enantioselective alkynylation of acrolein, the diastereoselective addition of a diynic ester to an epoxy aldehyde, and the asymmetric Sharpless epoxidation of allylic alcohol catalyzed with L-(+)-diethyl tartrate and Ti(OiPr)4. Graphical abstract image
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Stereoselective E/Z-photoisomerization of cyclooctene using 2,4-pentanediol chiral tether ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Kuifeng Song, Morifumi Fujita, Tadashi Okuyama, Takashi Sugimura The photoisomerization, epoxidation, and cyclopropanation of chiral 2,4-pentanediol tethered cyclooctene were explored to examine the stereocontrollability of the tether. Photoisomerization of (2R,4R)-2,4-pentanediol-tethered cyclooctene achieved a de of 20% at a high Z/E ratio of 0.80 at 25°C, while (2S,4R)-2,4-pentanediol-tethered cyclooctene yielded a lower de in spite of an even higher Z/E ratio. The epoxidation and cyclopropanation of 2,4-pentanediol tethered cyclooctene resulted in lower stereoselectivity compared with those of vinyl ether. We propose that the low de of the reactions of 2,4-pentanediol tethered cyclooctene is not attributable to the low stereocontrollability of 2,4-pentanediol tether, but due to the conformational multiplicity of the reactant site. Graphical abstract image
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Organocatalytic enantioselective conjugate addition of aldehydes to maleimides in deep eutectic solvents ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Jesús Flores-Ferrándiz, Rafael Chinchilla The conjugate enantioselective addition of aldehydes, mainly α,α-disubstituted, to maleimides leading to enantioenriched succinimides, has been achieved in recyclable deep eutectic solvents at room temperature. Enantiomerically pure carbamate-monoprotected trans-cyclohexane-1,2-diamines are used as organocatalysts, affording high yields and up to 94% ee of the final succinimides. The product can be extracted from the deep eutectic solvent, which retains the chiral organocatalyst, allowing both the solvent and catalyst to be reused. Graphical abstract image
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An investigation towards the diastereoselective synthesis of 3-acetoxy/methoxy/phthalimido-β-lactams using chiral imines ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Aman Bhalla, Garima Modi, S.S. Bari, Anu Kumari, Dipika Narula, Shiwani Berry The efficient diastereoselective synthesis of 3-acetoxy/methoxy/phthalimido-β-lactams 2/2′, 3/3′ and 4/4′ respectively was performed using chiral imines 1 obtained from chiral amines. Factors (solvent, temperature, substituent, steric bulk) influencing the stereoselectivity and the diastereomeric ratio were also studied in detail. The diastereoselectivity of the two isomers was determined from the ratio of integral values of doublets of C3–H and C4–H and from the integral values of H in –CH(Me/Et)Ph/Np of the two diastereomers. Representative pairs of cis-diastereomers were separated by efficient column chromatography. Graphical abstract image
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‘On water’ organocatalyzed enantioselective synthesis of highly functionalized cyclohexanones with an all-carbon quaternary centre from allylidene malononitriles and enones ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Ganga B. Vamisetti, Raghunath Chowdhury, Mukesh Kumar, Sunil K. Ghosh An organocatalyzed endo [4+2] cycloaddition between enones as pro-diene and allylidene malononitrile as dienophile leading to cyclohexanones with two 1,3-related stereogenic centres and an all-carbon quaternary centre has been developed. The reactions were performed under ‘green reaction’ conditions using water as the reaction medium and ambient conditions. When allylidene cyanoacetate was used as the dienophile, cyclohexanones with three contiguous stereogenic centres, one of which is an all-carbon quaternary centre, were formed. The products were obtained in high yield and with acceptable diastereo- and enantioselectivity. Graphical abstract image
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Enantioselective synthesis of new chiral 2-aziridinyl phosphonates and studies of their biological activities ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Özdemir Dogan, Sıdıka Polat Çakır, Nurzhan Beksultanova, Nurten Altanlar, Duygu Şimşek, Hasan Karabıyık A new series of chiral aziridinyl phosphonates has been synthesized and evaluated for antibacterial and antifungal activities. For the synthesis, a Gabriel-Cromwell reaction was used to form aziridinyl phosphonates in 52–83% yield. In order to evaluate antibacterial and antifungal activities, MIC values were measured. Although most of the compounds showed insignificant activity, two of them provided low to moderate antifungal activity. Graphical abstract image
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Novel MOP-type H8-binaphthyl monodentate phosphite ligands and their applications in transition metal-catalyzed asymmetric 1,4-conjugate additions and hydroformylations ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Mi Tian, Zeng-bo Pang, Hai-feng Li, Lai-lai Wang A new series of monodentate phosphites based on the rigid, axially chiral monoesterified H8-BINOL, which are easy to prepare from the readily accessible phosphorylating reagents (S a)- or (R a)-1,1′-binaphthyl-2,2′-diylchlorophosphite and (S a)- or (R a)-1,1′-H8-binaphthyl-2,2′-diylchlorophosphite, have been synthesized. All ligands were purified on a silica gel column under a nitrogen atmosphere with moderate yields, and were white solids and air-stable at room temperature. These ligands afforded good to excellent enantioselectivities in the Cu-catalyzed 1,4-conjugate addition of 2-cyclohexenone with nucleophiles Et2Zn (96% ee) and with Ph2Zn (65% ee), 2-cyclopentenone with Et2Zn (95% ee), 2-cycloheptenone with Et2Zn (76% ee), and 5,6-dihydro-2H-pyran-2-one with Et2Zn (90% ee). In the Rh-catalyzed asymmetric hydroformylation of styrene, these ligands showed a chemoselectivity of >99% in aldehydes, and a satisfactory branched over linear ratio (96/4). Moreover, the sense of the enantiodiscrimination of the products was mainly determined by the configuration of the BINOL-based or H8-BINOL-based phosphocycle. Graphical abstract image
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Enantioselective synthesis of (2R,13R,8Z)-2,13-diacetoxy-8-heptadecene, the major component of the sex pheromone of the pear leaf midge, Dasineura pyri ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Yun Zhou, Pengfei Yang, Shuoning Li, Lifeng Wang, Jingwei Yin, Jiangchun Zhong, Yanhong Dong, Shangzhong Liu, Min Wang, Qinghua Bian The first enantioselective synthesis of (2R,13R,8Z)-2,13-diacetoxy-8-heptadecene 1, the major component of the sex pheromone of the pear leaf midge, Dasineura pyri, has been achieved. The key steps include the (R,R)-BINOL/Ti(OiPr)4 catalyzed alkynylzinc addition to an unsaturated aldehyde, the ring-opening of the chiral epoxide with a Grignard reagent, and the partial reduction of an acetylenic diol ester to a (Z)-olefinic diol ester with hydrogen and P2-Ni. Graphical abstract image
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Stereoselective de novo synthesis of (5R)-3,4:5,6-di-O-isopropylidene-d-ribo-hexos-5-ulo-5,2-furanose ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Estefanía Dibello, Leopoldo Suescun, Gustavo A. Seoane, Daniela Gamenara A concise and stereoselective de novo synthesis of the protected oxidized sugar (5R)-3,4:5,6-di-O-isopropylidene-d-ribo-hexos-5-ulo-5,2-furanose is described. The synthetic sequence involves a stereoselective proline-catalyzed aldol reaction of an orthogonally protected l-glyceraldehyde derivative and 2,2-dimethyl-1,3-dioxan-5-one, to obtain 5-O-acetyl-6-O-benzyl-1,3-isopropylidene-l-psicose as a key intermediate, and the final product in 5 steps and 38% yield. Graphical abstract image
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Synthesis of enantiopure cyclic amino acid derivatives via a sequential diastereoselective Petasis reaction/ring closing olefin metathesis process ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Veronika A. Morozova, Irina P. Beletskaya, Igor D. Titanyuk A novel approach to the synthesis of enantiopure cyclic amino esters is reported. The utilization of allylboronic acid together with (S)-α-methylbenzylamine as a chiral auxiliary in the Petasis/Mannich reaction led to the formation of allylglycine derivatives in good yield and with high diastereoselectivity. Subsequent esterification, N-allylation followed by ring-closing metathesis (RCM) reaction enabled the preparation of enantiomerically pure cyclic α-amino acid derivatives. Graphical abstract image
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Enantioselective NHC-catalysed redox [4+2]-hetero-Diels-Alder reactions using α-aroyloxyaldehydes and unsaturated ketoesters ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): James E. Taylor, Alyn T. Davies, James J. Douglas, Gwydion Churchill, Andrew D. Smith N-Heterocyclic carbene (NHC)-catalysed redox [4+2]-hetero-Diels-Alder reactions of α-aroyloxyaldehydes with either β,γ-unsaturated α-ketoesters or α,β-unsaturated γ-ketoesters generates substituted syn-dihydropyranones in good yield with excellent enantioselectivity (up to >99:1 er). The product diastereoselectivity is markedly dependent upon the nature of the unsaturated enone substituent. The presence of either electron-neutral or electron-rich aryl substituents gives excellent diastereoselectivity (up to >99:5 dr), while electron-deficient aryl substituents give reduced diastereoselectivity. In these cases, the syn-dihydropyranone products are more susceptible to base-promoted epimerisation at the C(4)-position under the reaction conditions, accounting for the lower diastereoselectivity obtained. Graphical abstract image
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The stereochemistry of the 1,3-dipolar cycloadditions of diazomethane to pseudoguaianolides ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Adriana Ortiz-León, J. Martín Torres-Valencia, J. Jesús Manríquez-Torres, José G. Alvarado-Rodríguez, Carlos M. Cerda-García-Rojas, Pedro Joseph-Nathan The 1,3-dipolar cycloaddition of diazomethane to the sesquiterpene lactones, parthenin, coronopilin, and psilostachyin, gave their respective spiropyrazolines with complete chemoselectivity, while the diastereoselectivity in favour of the (11S)-stereoisomer was 86–98%. Similarly, mexicanin I acetate, helenalin, and helenalin acetate provided the (11R)-diastereoisomer. When helenalin and its acetate were treated with a large excess of diazomethane, they afforded their respective dipyrazolines with 98% diastereoselectivity in favour of the (2R,3S,11R)-diastereoisomer. All compounds were characterized by their physical and spectroscopic properties and their absolute configuration was established by X-ray diffraction analysis calculating the Flack and Hooft parameters. Graphical abstract image
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Enantioseparation of (RS)-atenolol with the use of lipases immobilized onto new-synthesized magnetic nanoparticles ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Adam Sikora, Dorota Chełminiak-Dudkiewicz, Marta Ziegler-Borowska, Michał Piotr Marszałł The enzymatic method was used for the direct resolution of racemic atenolol. The catalytic activities of commercially available lipases from Candida rugosa (MY and OF) immobilized onto new-synthesized chitosan magnetic nanoparticles [Fe3O4-CS-Et(NH2)2, Fe3O4-CS-Et(NH2)3] in the kinetic resolution of racemic atenolol were compared. The best results were obtained by using Candida rugosa lipase OF immobilized onto Fe3O4-CS-Et(NH2)3. Additionally, the enzyme reusability was investigated. It was established that even after 5 reaction cycles, both lipases from Candida rugosa maintained their high catalytic activities and operational stabilities. This approach is extremely important from an economical point of view, because it allows for a direct cost reduction of the biotransformation. Graphical abstract image
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Enantioselective alkylation of aromatic aldehydes with (+)-camphoric acid derived chiral 1,3-diamine ligands ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): M. Elisa Silva Serra, Dina Murtinho, Victória Paz A series of chiral 1,3-diamine ligands derived from (+)-camphoric acid were prepared from the reaction of 1,3-diamino-1,2,2-trimethylcyclopentane with aromatic aldehydes, followed by reduction of the corresponding diimines. These newly synthesized ligands were tested in the enantioselective alkylation of benzaldehyde with diethylzinc, giving 1-phenyl-1-propanol with enantiomeric ratios of up to 86:14. Our most selective ligand, derived from 2-methoxybenzaldehyde, was also tested in the alkylation of several aromatic aldehydes and product alcohols with enantiomeric ratios of up to 93.5:6.5 being observed in 2h at room temperature in the presence of 5mol% ligand. Graphical abstract image
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Stereochemistry abstracts ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
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Tetrahedron: Asymmetry Reports ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
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Cumulative author index ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
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Editorial board ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1
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Graphical contents list ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1
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Contributors to this issue ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1
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Conceptual defects of modern stereochemistry. Comprehensive remedy by stereoisograms based on RS-stereoisomerism for mediating between enantiomerism and stereoisomerism ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Shinsaku Fujita The recognition of chirality as a single kind of handedness is a conceptual defect of modern stereochemistry, which has caused serious confusion in its theoretical foundations and stereochemical nomenclature. To remedy this defect, RS-stereogenicity is developed as another kind of handedness. These two kinds of handedness are integrated to give RS-stereoisomerism, which is formulated diagrammatically by stereoisograms. During the process of the remedy, the lack of the concept of ligand reflections has been revealed as another conceptual defect. The lack of the concept of orbits (equivalence classes) has been found to be one more defect, which has caused a misleading classification of isomers. By adopting the concept of orbits, the revised hierarchy of isomerism is developed, i.e., isomers ⊇ isoskeletomers ⊇ stereoisomers ⊇ RS-stereoisomers ⊇ enantiomers ⊇ 3D-structures. Thereby, the theoretical foundations of modern stereochemistry are restructured rationally. Graphical abstract image
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A highly stereoselective and efficient synthesis of enantiomerically pure sitagliptin ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Sung Kwon Kang, Gyeong Hi Cho, Hyung Joon Leem, Bong Kwan Soh, Jaehoon Sim, Young-Ger Suh A highly stereoselective and efficient synthesis of sitagliptin 1 consisting of a chiral β-amino acid unit has been achieved through 6 steps from commercially available 2,4,5-trifluorobenzaldehyde 4. The chiral antidiabetic drug was obtained with almost perfect enantiomeric purity (>99.9% ee) in 40.9% overall yield. The key feature of the synthesis is the addition of a malonate enolate to a chiral sulfinylimine in more than 99:1 dr. Our synthetic procedure proved to be highly efficient, economical, and sustainable. Graphical abstract image
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Asymmetric synthesis of vicinal amino alcohols via organocatalytic sequential α-amination/Grignard addition reactions of aldehydes ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Can Liu, Jiang Weng, Zi-Hui Lin, Wei-Jie Huang, Jing Guo, Lin-Jie Huang, Gui Lu An organocatalytic sequential α-amination/Grignard addition reaction of aliphatic aldehydes is reported. The synthetically useful anti-vicinal amino alcohol derivatives were obtained in high yields and with high stereoselectivities. These derivatives could be easily transformed into oxazolidinones. Graphical abstract image
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Synthesis of chiral hydantoin derivatives by homogeneous Pd-catalyzed asymmetric hydrogenation ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Bao-De Ma, Sheng-Hua Du, Yu Wang, Xiao-Ming Ou, Ming-Zhi Huang, Li-Xin Wang, Xiao-Guang Wang 5-Aryl substituted chiral hydantoin derivatives were synthesized via asymmetric hydrogenation of prochiral exocyclic alkenes using a Pd/BINAP catalyst. Moderate to good enantioselectivity were obtained (21–90% ee). A chiral Brönsted acid additive was found to be a key factor to obtain high enantioselectivity. Graphical abstract image
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Synthesis of fluorine-substituted [2.2]paracyclophane-based carbene precursors for copper-catalyzed enantioselective boration of α,β-unsaturated ketones ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Linyong Wang, Meng Ye, Lei Wang, Wenzeng Duan, Chun Song, Yudao Ma Fluorine-substituted [2.2]paracyclophane-based carbene precursors have been successfully synthesized and applied to copper-catalyzed asymmetric β-boration of α,β-unsaturated ketones. Fluorination of the planar chiral carbenes has a beneficial impact on the catalytic performance of the relevant complexes. A variety of chiral β-boryl ketones were obtained in excellent yields (up to 99%) and with high enantioselectivities (up to 99% ee). Graphical abstract image
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Rhodium/zinc co-catalyzed asymmetric ring opening reactions of oxabenzonorbornadienes with carboxylic acids ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Xiaobo He, Jingchao Chen, Xin Xu, Fan Yang, Cuiping Gu, Yongyun Zhou, Baomin Fan The asymmetric ring opening reactions of oxabenzonorbornadienes with carboxylic acids are described. By using the complex of [Rh(COD)Cl]2 and (S,S)-BDPP, with ZnI2 as the co-catalyst, a range of aromatic acids and alkyl acids were utilized as nucleophiles to afford the corresponding chiral hydronaphthalene products with high enantioselectivities (84–94% ee). Thus, the present methodology has provides an effective synthetic method for the preparation of enantioenriched hydronaphthalenes. Graphical abstract image
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Synthesis of a novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid and application to the asymmetric catalytic Biginelli reaction ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Xiaoyun Hu, Rui Zhang, Jinsheng Xie, Zhongqiang Zhou, Zixing Shan A novel sterically hindered chiral cyclic phosphoric acid derived from l-tartaric acid was designed and synthesized based on highly regioselective cyclosulfitation of chiral 1,1,4,4-tetraphenylbutanetetraol. The asymmetric Biginelli reaction catalyzed by this newly synthesized chiral phosphoric acid was examined, and enantioselectivities up to 99% ee was obtained. Graphical abstract image
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Convenient green preparation of dipeptides using unprotected α-amino acids ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Tetsuya Ezawa, Seunghee Jung, Yuya Kawashima, Takuya Noguchi, Nobuyuki Imai Dipeptides and amides were obtained in high yields from N-carbobenzyloxy α-amino acids and 3-phenylpropanoic acid with unprotected α-amino acids via the corresponding mixed carbonic carboxylic anhydrides using ethyl chloroformate and triethylamine by an ecological and convenient method in which the protection of C-terminals is not needed. Graphical abstract image
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The PMe3-catalyzed addition of enantiomerically pure (−)-MenthylO(Ph)P(O)H to electron-deficient alkenes: an efficient way for the preparation of P-stereogenic compounds ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Yuta Saga, Yuka Mino, Shin-ichi Kawaguchi, Daoqing Han, Akiya Ogawa, Li-Biao Han A variety of P-stereogenic organophosphorus compounds can be readily prepared by stereoretentive addition. The PMe3-catalyzed addition of optically active (−)MenthylO(Ph)P(O)H compounds to electron deficient alkenes occur stereospecifically, to produce the corresponding P-stereogenic adducts in high yields. By simply removing the volatiles under vacuum, spectroscopically pure products can be obtained. The present method provides a salt-free clean process for the preparation of P-chiral organophosphorus compounds. Graphical abstract image
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Chiral thiophosphoramide catalyzed asymmetric aryl transfer reactions for the synthesis of functional diarylmethanols ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Yabai Wang, Hua Zong, Huayin Huang, Ling Song In this investigation, chiral thiophosphoramide 3d was easily prepared from chiral (1R,2R)-1,2-diphenylethylenediamine and then applied as an efficient chiral ligand in the catalytic asymmetric arylation reactions of various aromatic aldehydes. The corresponding diarylmethanol products were produced with good to excellent yields (up to 98%) and enantioselectivities (up to 94%). The recovery of chiral ligand 3d could be as high as 96%. Graphical abstract image
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syn-Diastereoselective glycolate aldol addition reactions of an N(3)-(p-methoxyphenoxy)acetyloxazolidine-2-thione ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Craig S. Haynes, Cassie A. Goodman, Juandah Bruce, Sarah C. Genin, Brad J. Austermuehle, Victor L. Leong, Austin R. Leise, Robert Larson, Christopher G. Hamaker, Shawn R. Hitchcock An N 3-(p-methoxyphenoxy)acetyloxazolidine-2-thione has been synthesized and employed in glycolate asymmetric aldol addition reactions with aromatic and aliphatic aldehydes. It was determined that the titanium tetrachloride medicated aldol reaction afforded diastereoselectivities that ranged from 75:25 to 94:6 when the reaction was conducted at −78°C. The absolute stereochemistry of the aldol adducts was determined by 1H NMR spectroscopy and X-ray crystallography. The 1H NMR spectra of the aldol adducts contained a signal (the α-proton of the glycolate position of the aldol side chain) that was highly deshielded due to conformational restriction about the N(3)-(p-methoxyphenoxy)acetyl side chain and the oxazolidine-2-thione auxiliary. Graphical abstract image
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Formal asymmetric synthesis of (+)-tofacitinib ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Hao-Chun Liao, Biing-Jiun Uang Tofacitinib is an efficient and selective Janus kinase 3 (JAK3) inhibitor, and is used as an immunosuppressant drug for the treatment of rheumatoid arthritis and transplant patients. Herein we report a concise formal asymmetric synthesis of tofacitinib from homochiral 1,3-dioxolanone 10b, which was elaborated through a highly stereoselective Michael addition followed by solvent-free removal of the chiral auxiliary and ring cyclization to furnish chiral imide 8. The preparation of tofacitinib’s precursor 16 could be obtained after reduction of 8 followed by sequential oxidation, reductive amination and SNAr reactions. Graphical abstract image
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Enantioselective synthesis of new oxazolidinylthiazolidines as enzyme inhibitors ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Cecilia Saiz, Valentina Villamil, Mariano M. González, Ma. Agustina Rossi, Lorena Martínez, Leopoldo Suescun, Alejandro J. Vila, Graciela Mahler The synthesis of new oxazolidinylthiazolidines bicycles, oxygen analogues of bisthiazolidines, also known as metallo-β-lactamase inhibitors is described. The reaction of β-aminoalcohols and 2,5-dihydroxy-1,4-dithiane led to oxazolidinylthiazolidines and/or dithioazabicycles as the main products. The distribution pattern depends mainly on the aminoalcohol substituents. In a one-pot reaction, four new bonds are formed in good yields and with high atom efficiency. When the oxazolidinylthiazolidines are formed, two stereogenic centres are generated with high enantiospecificity. The reaction mechanism is discussed based on crystallographic data and interconversion studies. Two oxazolidinylthiazolidines were evaluated as inhibitors of the potent lactamase NDM-1 and compound 4f displayed competitive inhibition with Ki =1.6±0.6μM. Graphical abstract image
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Chemoenzymatic route to optically active dihydroxy cyclopenta[b]naphthalenones; precursors for decalin-based bioactive natural products ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Devrim Özdemirhan, Özlem Sarıçelik The development of an efficient chemoenzymatic route for the synthesis of optically active dihydroxy cyclopenta[b]naphthalenones; (+)-1,4a-dihydroxy-4a,5,6,7,8,8a,9,9a-octahydro-1H-cyclopenta[b]naphthalen-2(4H)-one (+)-10 and (+)-1,8a-dihydroxy-4a,5,6,7,8,8a,9,9a-octahydro-1H-cyclopenta[b]naphthalen-2(4H)-one (+)-11 is described. Different lipases and esterases were tested in the enzymatic hydrolysis of the corresponding acetates (±)-4a-hydroxy-2-oxo-2,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-cyclopenta[b]naphthalen-1-yl acetate (±)-8, (±)-8a-hydroxy-2-oxo-2,4,4a,5,6,7,8,8a,9,9a-decahydro-1H-cyclopenta[b]naphthalen-1-yl acetate (±)-9, CRL (Candida Rugosa Lipase) and PLE (Pig Liver Esterase) were found to be the most effectual enzymes; for (−)-8 by 47% ee with the corresponding dihydroxy; (+)-10 by 98% ee in the presence of CRL; whereas, (−)-8 was obtained with 40% ee with the corresponding dihydroxy, (+)-10 with 58% ee in the PLE hydrolysis. It was concluded that CRL was the best biocatalyst for the substrate (±)-8. Moreover, enzymatic resolution in the presence of CRL yields, (−)-9 with 46% ee with the corresponding dihydroxy derivative; (+)-11 with 98% ee; however, in the presence of PLE, yields (−)-9 with 36% ee as well as the related dihydroxy derivative; (+)-11 with 49% ee respectively. The study concluded that CRL is the best biocatalyst for compounds (±)-8 and (±)-9. Graphical abstract image
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Enantioselective N-heterocyclic carbene catalyzed formal [3+2] cycloaddition using α-aroyloxyaldehydes and oxaziridines ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Ryan W.F. Kerr, Mark D. Greenhalgh, Alexandra M.Z. Slawin, Polly L. Arnold, Andrew D. Smith An enantioselective N-heterocyclic carbene catalysed formal [3+2] cycloaddition has been developed for the synthesis of oxazolindin-4-one products. The reaction of oxaziridines and α-aroyloxyaldehydes under N-heterocyclic carbene catalysis provides the formal cycloaddition products with excellent control of the diastereo- and enantioselectivity (12 examples, up to >95:5 dr, >99:1 er). A matched-mismatched effect between the enantiomer of the catalyst and oxaziridine was identified, and preliminary mechanistic studies have allowed the proposal of a model to explain these observations. Graphical abstract image
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Properties and separation method of enantiomers of the mono- and bis-substituted derivatives of 3,3′,4,4′-tetramethyl-1,1′-diphosphaferrocene: structural analysis using X-ray diffraction and circular dichroism ()
Publication date: 15 January 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 1 Author(s): Arkadiusz Kłys, Anna Makal, Anna Zdzienicka This work expands on the recent separation of the enantiomers of the C 2-symmetrical bis-substituted derivatives of 1,1′-diphosphaferrocene. The effective separation of mono-substituted 1,1′-diphosphaferrocenes by the proposed method is demonstrated. The absolute configuration of the three separated components was established using X-ray diffraction. Circular dichroism spectra were collected for all of the separated compounds. The spectrum of each compound shows a characteristic curve, and the curves for the enantiomers are symmetrical. We also show that the correct absolute configuration for similar species can be assigned on the basis of the obtained data. We propose an explanation for the abnormal 1H NMR spectra of phospholyl protons in some derivatives of 1,1′-diphosphaferrocene. A density functional theory (DFT) study of the conformation, as well as circular dichroism and NMR spectra of the chosen species, is also presented. Graphical abstract image
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