Tetrahedron Asymmetry

Influence of solvent polarity on the separation of leucine enantiomers by β-cyclodextrin: a molecular mechanics and dynamics simulation ()
Publication date: Available online 13 October 2017 Source:Tetrahedron: Asymmetry Author(s): Elena Alvira The interaction between leucine and β-cyclodextrin with different solvents was studied by molecular mechanics and dynamics simulations. In order to analyse the influence of the solvent polarity on the inclusion complex formation and separation process of leucine enantiomers by β-cyclodextrin, the organic modifiers were characterised by the same value of dielectric constant in the electrostatic contribution to the interaction energy, and a different molecular configuration of amino acids (neutral or zwitterion). The complexes formed in polar solvents were more stable than those in non-polar solvents with the same dielectric constant, because the electrostatic contribution is negative for the former and positive for the latter. The optimized structures obtained for leucine enantiomers and β-cyclodextrin in vacuo are non-inclusion complexes. The solvent polarity contributes to increasing the probability of the presence in an inner position for the guest, whereas the results for non-polar configurations were smaller and distributed in larger areas. The regions where the enantiomers spend more time in the simulation correspond to locations with greater chiral discrimination. d-Leu was the first eluted enantiomer in every case, except for a polar solvent with ε = 26 . Graphical abstract image
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A fast, new method to enhance the enantiomeric purity of non-racemic mixtures: self-disproportionation of enantiomers in the gas antisolvent fractionation of chlorine-substituted mandelic acid derivatives ()
Publication date: Available online 13 October 2017 Source:Tetrahedron: Asymmetry Author(s): Márton Kőrösi, János Madarász, Tamás Sohajda, Edit Székely Gas antisolvent precipitation is a particle formation technique, when typically pressurized carbon dioxide is added to an organic solution resulting in immediate and high oversaturation and precipitation of fine particles. Provided that a reasonable share of the originally dissolved material remains dissolved in the carbon dioxide – organic mixed solvent, these components can be extracted during the washing phase. This method is called gas antisolvent fractionation. Gas antisolvent fractionation has been applied for the first time to enantiomeric enrichment of non-racemic mixtures, and demonstrated on the example of chlorinated mandelic acid derivatives. Due to self-disproportionation of enantiomers, the precipitated solid and the extracted fractions have different enantiomeric excesses if gas antisolvent fractionation is carried out on a non-racemic mixture. However, there is a limit in the enantiomeric excess (ee) that can be achieved correlating strongly with the atmospheric melting eutectic behavior of the compounds. Thus, if initial enantiomeric mixtures have a higher than eutectic ee, a >99% ee can be reached in the crystalline product. The strong correlation between the high-pressure experiments and the atmospheric melting eutectic behavior suggest that despite the very large oversaturation during the antisolvent precipitation, the composition of the products (i.e., the crystalline and the extracted phases) is thermodynamically determined. Technological advantages such as short operational time, or the possibility of controlling the crystal morphology suggest that the development of an efficient technique of enantiomeric purification is possible based on gas antisolvent fractionation. Graphical abstract image
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Asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680 ()
Publication date: Available online 13 October 2017 Source:Tetrahedron: Asymmetry Author(s): Stephen G. Davies, Ai M. Fletcher, Abigail R. Hanby, Paul M. Roberts, James E. Thomson The asymmetric syntheses of the N-terminal α-hydroxy-β-amino acid components of microginins 612, 646 and 680 are reported. Conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to the requisite (E)-α,β-unsaturated ester followed by in situ enolate oxidation with (−)-(camphorsulfonyl)oxaziridne (CSO) gave the corresponding anti-α-hydroxy-β-amino esters. Sequential Swern oxidation followed by diastereoselective reduction gave the corresponding syn-α-hydroxy-β-amino esters. Subsequent N-debenzylation (i.e., hydrogenolysis for microginin 612, and NaBrO3-mediated oxidative N-debenzylation for microginins 646 and 680) followed by acid catalysed ester hydrolysis gave the corresponding syn-α-hydroxy-β-amino acids, the N-terminal components of microginins 612, 646 and 680, in good yield. An analogous strategy for elaboration of the enantiopure anti-α-hydroxy-β-amino esters facilitated the asymmetric synthesis of the corresponding C(2)-epimeric α-hydroxy-β-amino acids. Graphical abstract image
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Catalytic asymmetric synthesis of Leukotriene B4 ()
Publication date: Available online 13 October 2017 Source:Tetrahedron: Asymmetry Author(s): Pengfei Yang, Jiangchun Zhong, Kaijie Ji, Jingwei Yin, Shuoning Li, Siyuan Wei, Yun Zhou, Lifeng Wang, Min Wang, Qinghua Bian Leukotriene B4 1 was prepared from two chiral synthons 8 and 14. The chiral secondary alcohols of 8 and 14 were constructed by BINOL/Ti(OiPr)4 catalyzed enantioselective alkynylzinc addition to aldehydes. Graphical abstract image
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Pd(II) complexes of monodentate deoxycholic acid derived binaphthyl diamido phosphites as chiral catalysts in the asymmetric Suzuki-Miyaura cross-coupling ()
Publication date: Available online 13 October 2017 Source:Tetrahedron: Asymmetry Author(s): Grazia Iannucci, Vincenzo Passarelli, Alessandro Passera, Anna Iuliano Chiral binaphthyl diamidophosphites derived from deoxycholic acid were synthesized and used as ligands for the preparation of mononuclear Pd(II) complexes, which were employed as catalysts in the asymmetric Suzuki-Miyaura cross-coupling of arylboronic acids with aryl bromides. Among the different reaction parameters, the substrate concentration emerged as being crucial for the outcome of the reaction: the reaction was faster in a concentrated reaction mixture, and could be performed at 0°C, where the reaction promoted by the Pd-complexes was more enantioselective affording cross-coupling products with ee up to 70%. Graphical abstract image
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Some experimental aspects of absolute configuration determination using single crystal X-ray diffraction ()
Publication date: Available online 12 October 2017 Source:Tetrahedron: Asymmetry Author(s): Amber L. Thompson, Sarah F. Jenkinson, George W.J. Fleet Students of single crystal X-ray diffraction are often give advice as to how best to collect their data when attempting absolute configuration determination. These ‘rules’ often have more grounding in gut-feeling than evidence. Thus, in an effort to provide advice and evidence that today’s crystallographers can pass onto to tomorrow’s young scientists, we present a systematic study of 1-deoxy-l-arabinitol, a straight chain sugar which crystalises well in the space group I 4 1 .
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Some new protocols for the assignment of absolute configuration by NMR spectroscopy using chiral solvating agents and CDAs ()
Publication date: Available online 12 October 2017 Source:Tetrahedron: Asymmetry Author(s): Sandeep Kumar Mishra, Nagarajarao Suryaprakash The utility of enantiopure BINOL (1,10-Bi-2-naphthol), in a ternary ion-pair complex, which is obtained using a carboxylic acid and an organic base, as a versatile chiral solvating agent (CSA) has been demonstrated for chiral analysis and the absolute configuration assignment of hydroxy acids. Another protocol where the utility of NOBIN as a CSA has been developed for discrimination and absolute configuration assignment of acids, hydroxy acids and their derivatives with a distinct strategy where a third ingredient, p-toluenesulfonic acid (p-TsOH) serves as a linker. In addition some three component chiral derivatization protocols have been introduced, such as the use of 2-formylphenylboronic acid and enantiopure mandelic acid or a primary amine for the determination of the configuration of primary amines and hydroxy acids, respectively. A simple, rapid and highly efficient three component chiral derivatizing protocol has also been discussed which was developed for assigning the absolute configuration of chiral α-hydroxy acids and their derivatives, which involves the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and (S)-[1,1-binaphthalene]-2,2-diamine separately. In a few examples, the DFT based theoretical calculations have been carried out to determine the geometry optimized structures of the complexes. Graphical abstract image
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Chiroptical spectroscopy and the validation of crystal structure stereochemical assignments ()
Publication date: Available online 10 October 2017 Source:Tetrahedron: Asymmetry Author(s): George E. Tranter, Delphine D. Le Pevelen The absolute stereochemistry of chiral molecules is ideally established to atomic resolution by X-ray crystallographic analysis. However, chiroptical spectroscopies, namely electronic circular dichroism (ECD), optical rotatory dispersion (ORD), vibrational circular dichroism (VCD) and Raman optical activity (ROA), play important complementary roles in establishing relative and absolute sterochemistries as well as allowing determinations of optical purity. A brief summary of chiroptical spectroscopies is presented, along with guidance to their advantages and disadvantages. The application of ECD to verifying that single crystals selected for crystallographic analysis are indeed representative of bulk material is described. Graphical abstract image
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Thermal racemization of biaryl atropisomers ()
Publication date: Available online 9 October 2017 Source:Tetrahedron: Asymmetry Author(s): Darshan C. Patel, Ross M. Woods, Zachary S. Breitbach, Alain Berthod, Daniel W. Armstrong Many biaryl compounds possess atropisomerism due to the steric hindrance of substituents at the ortho-position of the two aromatic moieties. Upon heating, atropisomers may have enough energy to surpass the rotational energy barrier and racemize. The thermal stability of five atropisomers was studied using chiral chromatography by following the change in enantiomeric excess ratio at different temperatures. The first order racemization reaction rate was obtained at a given temperature as the slope of the change in enantiomeric excess ratio versus time. For each atropisomer, the racemization rates at different temperatures led to the value of the rotational energy barrier for racemization, ΔG ‡, and to the racemization half lifetime, t 1/2, indicating the atropisomer thermal stability. Binaphthol started to racemize significantly at temperature of 190°C and above while binaphthyldiamine was much more stable showing little or very minor racemization up to 210°C. A chloro-substituted phenylamino-naphthol was very sensitive to thermal racemization starting at a low 40°C. Graphical abstract image
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Features of electronic circular dichroism and tips for its use in determining absolute configuration ()
Publication date: Available online 9 October 2017 Source:Tetrahedron: Asymmetry Author(s): Jesús T. Vázquez This review focuses on the general features of electronic circular dichroism (ECD) as applied in determining the absolute configuration of organic compounds. The high sensitivity and straightforward spectral interpretation of the exciton chirality method makes this approach very useful, and complementary to X-ray crystallography. A brief tutorial is provided on ECD, with precautions and tips for using it, especially the exciton chirality method. The spectroscopic ECD of several examples are analyzed. Graphical abstract image
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Synthesis and crystal structure of a chiral lactam and three amino alcohols as potential protein tyrosine phosphates 1B inhibitors ()
Publication date: Available online 9 October 2017 Source:Tetrahedron: Asymmetry Author(s): Şafak Özhan Kocakaya, Mehmet Karakaplan, Rosario Scopelliti Chiral lactam 2 and three chiral β-amino alcohols 3–5 have been synthesized and characterized by spectroscopic techniques. Regioselective ring opening reaction of chiral styrene oxide by an amine nucleophile was confirmed by X-ray diffraction data. Ligand 2–4 crystallizes in the tetragonal, orthorhombic and tetragonal crystal lattice system respectively. Ligands 2–6 have been used as potential inhibitors for protein tyrosine phosphatase 1B enzyme (PTP1B). The potential inhibitor effect of these molecules to the target protein was investigated by Dock and molecular dynamics calculations. Dock score analysis and Lipinski parameters suggested that ligands 1, 2, 4–6 are potential inhibitors towards PTP1B, thus indicating that the residues Arg24, Arg254 and Met258, Asp29 in the second active site of PTP1B are essential for the high selectivity of inhibitors. The results indicate that the polar hydrogen bonding interacts with Asp29, Gln102, and the amino acid residues of PTP1B are responsible for governing inhibitory potency of ligands 1–6. Graphical abstract image
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Asymmetric epoxidation of enones using cumyl hydroperoxide and in situ generated zinc complexes of chiral pyrrolidinyl alcohols ()
Publication date: Available online 7 October 2017 Source:Tetrahedron: Asymmetry Author(s): Halide Sedef Karaman, Hamdullah Kılıç, Engin Şahin The homogeneous asymmetric epoxidation of a range of enones was carried out using cumyl hydroperoxide, diethylzinc, and chiral pyrrolidinyl alcohol-containing ligands to afford the corresponding epoxy ketones with enantioselectivities of ≤97% ee. Examination of the enantioselectivities obtained in the asymmetric epoxidation of enones using a range of chiral ligands indicated that synergy between the sterically bulky bicyclo[2.2.2]octane skeleton and the substituents attached to the carbinol moiety played an important role in determining the reaction enantioselectivity. The position and nature of the substituent on the aromatic ring of the enone also had a pronounced effect on the observed enantioselectivity. Graphical abstract image
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Diastereoselective and enantioselective alkaline-hydrolysis of 2-aryl-1-cyclohexyl acetate: a CAL-B catalyzed deacylation/acylation tandem process ()
Publication date: Available online 7 October 2017 Source:Tetrahedron: Asymmetry Author(s): Fatma Zahra Belkacemi, Mounia Merabet-Khelassi, Louisa Aribi-Zouioueche, Olivier Riant Candida antarctica lipase proved to be a particularly efficient lipase for the resolution of racemic 2-arylcyclohexyl acetate in hydrolysis reaction with Na2CO3 in an organic medium. The (1R,2S)-trans-2-arylcyclohexanols 2a–2d were obtained with high ee values (up to >99%) and the selectivity reached E >200. The influence of the enol ester and the solvent on (±)-trans-2-arylcyclohexanol in the CAL-B catalyzed acylation was also studied and compared with the deacylation. The CAL-B exhibits a better affinity for the alkaline hydrolysis reaction compared with acylation with the enol esters in the same organic solvents. The best conditions were applied to resolve a stereoisomeric mixture cis/trans-2-phenyl-1-cyclohexanol and its corresponding acetate by acylation and deacylation. The obtained results show a highly enantio- and diastereoselectivity of the CAL-B during the acylation and the deacylation in favor of the trans-(R)-enantiomer product. The resolution of a mixture of cis/trans-2-arylcyclohexanols was an easy, convenient approach to provide only one stereoisomer of a mixture of four with high enantiomeric excess. Graphical abstract image
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Ferrocene derivatives of liquid chiral molecules allow assignment of absolute configuration by X-ray crystallography ()
Publication date: Available online 6 October 2017 Source:Tetrahedron: Asymmetry Author(s): Philipp M. Holstein, Julian J. Holstein, Eduardo C. Escudero-Adán, Olivier Baudoin, Antonio M. Echavarren The present study investigates a synthetically simple ferrocene derivatization of natural products and active pharmaceutical ingredients. Seven new crystal structures are analyzed together with 16 structures of ferrocene derivatives reported previously. In all cases, the unambiguous determination of the absolute structure was established from anomalous dispersion using the methods of Flack and Parsons. A comparison with other derivatization approaches shows the advantage of the described ferrocene derivatization for establishing the absolute configuration of novel compounds. Graphical abstract image
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Nucleophilic additions on acetyldioxanes derived from (−)-(1R)-myrtenal used as chiral auxiliaries: substituent effects on the stereochemical outcome ()
Publication date: Available online 6 October 2017 Source:Tetrahedron: Asymmetry Author(s): Elvia Becerra-Martínez, Francisco Ayala-Mata, Pedro Velázquez-Ponce, Manuel E. Medina, Hugo A. Jiménez-Vazquez, Pedro Joseph-Nathan, L. Gerardo Zepeda The synthesis of acetyldioxanes 4 and 9a starting from (−)-(1R)-myrtenal is described. The products were treated with a representative series of nucleophilic reagents (RMgX, RLi, NaBH4 and LiAlH4) to assess the effect of the substituent at C-3 on the stereochemical outcome. It was observed that the nucleophiles preferred the re-face of the CO group when the equatorial substituent at C-3 was a methyl group, whereas a phenyl group at the same position induced the addition through the si-face, thus allowing access to either desired stereochemistry of a final product. This behavior suggests that the formation of the expected Cram-chelated coordination complex takes a coplanar orientation with the C-3 equatorial substituent. Moreover, Grignard reagents were the most stereoselective nucleophiles. The stereochemistry of the addition was established by X-ray diffraction and chemical correlation. Graphical abstract image
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Synthesis of the four enantiomers of diethyl 1,2-di(N-Boc-amino)propylphosphonates ()
Publication date: Available online 5 October 2017 Source:Tetrahedron: Asymmetry Author(s): Iwona E. Głowacka, Dorota G. Piotrowska, Andrzej E. Wróblewski, Aleksandra Trocha A simple and efficient synthetic strategy to all four enantiomerically pure diethyl 1,2-di(N-Boc-amino)propylphosphonates has been elaborated starting from the corresponding N-[(R)-(1-phenylethyl)]aziridine-(2S)- and N-[(S)-(1-phenylethyl)]aziridine-(2R)-carboxaldehydes, employing a one-pot three-components Kabachnik-Fields reaction followed by the hydrogenolytic removal of the chiral auxiliary and aziridine ring opening with simultaneous protection of the amino groups as the N-Boc derivatives. Graphical abstract image
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Chiral benzimidazoles and their applications in stereodiscrimination processes ()
Publication date: Available online 3 October 2017 Source:Tetrahedron: Asymmetry Author(s): Vaibhav N. Khose, Marina E. John, Anita D. Pandey, Anil V. Karnik Chiral aspects of benzimidazoles have been over-shadowed for a long time due to the large number of reports on benzimidazoles in the medical field in numerous categories of therapeutic agents. The vigorous research activity in chiral applications of benzimidazole derivatives started after bifunctional benzimidazoles made their appearance especially in the last 2–3 decades. Thus, chiral benzimidazoles form a comparatively young branch of chiral chemistry. The presence of pyridine and pyrrole type of nitrogens along with the fused benzene ring confer on this class of molecules, special properties including useful nucleophilicity, hydrogen bonding ability and a rigid backbone, all of which play decisive roles in proven chiral applications. The present review aims to cover the synthetic routes to access chiral benzimidazoles and their applications in a plethora of chiral fields including enantioselective organocatalysis, metal-based catalysis, asymmetric transformations involving benzimidazole-N-heterocyclic carbenes, kinetic resolution, benzimidazole-based macrocyclic hosts in chiral supramolecular chemistry and other miscellaneous chiral applications. Graphical abstract image
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Strategies for using NMR spectroscopy to determine absolute configuration ()
Publication date: Available online 28 September 2017 Source:Tetrahedron: Asymmetry Author(s): Thomas J. Wenzel General strategies by which NMR spectroscopy can be used to assign absolute configuration are discussed. These include the use of chiral derivatizing and chiral solvating agents. Areas that are well developed and areas of need in this field are described. The future potential of using aligning media such as chiral liquid crystals and odd-parity effects that may make it possible to determine absolute configuration without the need for an enantiomerically pure reagent are discussed. Graphical abstract image
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Tartaric acid-derived chiral phosphite-type P,N-ligands: behavioural features in Pd-catalyzed asymmetric transformations ()
Publication date: Available online 28 September 2017 Source:Tetrahedron: Asymmetry Author(s): Konstantin N. Gavrilov, Sergey V. Zheglov, Ilya V. Chuchelkin, Marina G. Maksimova, Ilya D. Firsin, Andrew N. Fitch, Vladimir V. Chernyshev, Alexander V. Maximychev, Alexander M. Perepukhov A practical synthesis of new phosphoramidite, phosphite and diamidophosphite P,N-ligands derived from (R,R)-tartaric acid was carried out. A study of these chiral inducers showed them to provide up to 93% ee in the Pd-catalyzed asymmetric allylations of (E)-1,3-diphenylallyl acetate, up to 84% ee in the Pd-catalyzed asymmetric alkylation of cinnamyl acetate with ethyl 2-oxocyclohexane-1-carboxylate and up to 63% ee in the Pd-catalyzed desymmetrization of N,N′-ditosyl-meso-cyclopent-4-ene-1,3-diol biscarbamate. The effects of the structural modules, such as the nature of the phosphorus-containing ring or exocyclic substituent as well as of the nature of palladium source on the catalytic activity and enantioselectivity were investigated. Graphical abstract image
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An asymmetric synthesis of (+)-monomorine I ()
Publication date: Available online 26 September 2017 Source:Tetrahedron: Asymmetry Author(s): Masaki Asai, Yukiko Takemoto, Ayaka Deguchi, Yasunao Hattori, Hidefumi Makabe The synthesis of (+)-monomorine I, an indolizidine alkaloid isolated from Monomorium pharaonis, has been achieved. The 2,6-cis-piperidine ring moiety of (+)-monomorine I was constructed using diastereoselective aminopalladation. Chain elongation via cross-metathesis using Hoveyda-Grubbs 2nd catalyst followed by deprotection of the Cbz group and cyclic reductive hydroamination afforded (+)-monomorine I. Graphical abstract image
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Determination of absolute configuration using X-ray diffraction ()
Publication date: Available online 22 September 2017 Source:Tetrahedron: Asymmetry Author(s): Simon Parsons Methods for determination of absolute structure using X-ray crystallography are described, with an emphasis on applications for absolute configuration assignment of enantiopure light-atom organic compounds. The ability to distinguish between alternative absolute structures by X-ray crystallography is the result of a physical phenomenon called resonant scattering, which introduces small deviations from the inherent inversion symmetry of single-crystal X-ray diffraction patterns. The magnitude of the effect depends on the elements present in the crystal and the wavelength of the X-rays used to collect the diffraction data, but it is always very weak for crystals of compounds containing no element heavier than oxygen. The precision of absolute structure determination by conventional least squares refinement appears to be unduly pessimistic for light-atom materials. Recent developments based on Bijvoet differences, quotients and Bayesian statistics enable better and more realistic precision to be obtained. The new methods are sensitive to statistical outliers, and techniques for identifying these are summarised. Graphical abstract image
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Editorial board ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9
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Graphical contents list ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9
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Contributors to this issue ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9
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A closer look on various synthetic routes to Callystatin A: a cytotoxic marine sponge polyketide ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Aamer Saeed, Babar Hussain Shah, Rabia Qamar Callystatin A, a polyketide marine natural product, has been known since 1997 after its isolation from the sponge Callyspongia truncata by Kobayashi et al. It belongs to the leptomcyin family of natural products with a highly conjugated and stereodefined skeleton. The challenging structural topographies and remarkable anti-proliferative properties of (−)-Callystatin A stimulated many researchers to pursue the total synthesis of this marine polyketide. This review is exclusively focused on the research undertaken towards the concise, asymmetric total synthesis of Callystatin A over the last two decades. The various target oriented synthetic pathways are discussed in a chronological order to give a comprehensive overview. Graphical abstract image
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Studies on asymmetric synthesis of bicyclomycin precursors. A chemoenzymatic route to chiral 2,5-diketopiperazines and 2-oxa-bicyclo[4.2.2]decane-8,10-diones ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Anna Fryszkowska, Dominik Koszelewski, Ryszard Ostaszewski A novel asymmetric route to bicyclomycin analogues, 2-oxa-bicyclo[4.2.2]decane-8,10-diones, is described. The key chiral synthons 3-(ω-hydroxyalkyl)-2,5-diketopiperazines 3a-c were obtained via enzymatic kinetic resolution of their respective acetates 2a-c using hydrolases (up to >98% ee, E >200). The chiral 2,5-diketopiperazines were then transformed into their bicyclic derivatives in a stereospecific manner. Circular dichroism and NMR studies were performed to determine the absolute and relative configuration of the obtained products. The biocatalytic approach gave high stereoselectivities in comparison to the chiral pool synthesis from glutamic acid (58% ee) and thus demonstrated the ability of hydrolases to discriminate a remote stereocenter. Graphical abstract image
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On the absolute configuration of 1-cyclopropylethan-1-amine ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Matthew W.D. Perry, Anders Eriksson, Marie Rydén Landergren We observed a discrepancy between the reported specific rotation for the enantiomers of 1-cyclopropylethan-1-amine and the values for commercial material. Analyses by VCD of the free amine, by NMR analysis of the derived (S)-O-methylmandelamides and an X-ray crystal structure of one of the mandelamides defined the specific rotation for each enantiomer. Graphical abstract image
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A diversity oriented synthesis of d-erythro-sphingosine and siblings ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Amrita Ghosh, Shital K. Chattopadhyay An efficient building block-based synthetic protocol has been developed for the synthesis of 3-ketosphingoids with various chain lengths using cross metathesis of a Garner’s aldehyde-derived α,β-unsaturated ketone as the key step. Stereoselective reduction of the biomimetic precursors thus obtained provided d-erythro-sphingosine and truncated anaogues in good overall yields. Graphical abstract image
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Impact of variation of the acyl group on the efficiency and selectivity of the lipase-mediated resolution of 2-phenylalkanols ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Aoife M. Foley, Declan P. Gavin, Ilona Joniec, Anita R. Maguire By tuning the steric properties of the acyl group to control the efficiency and selectivity of the resolution, 2-phenyl-1-propanol 1a was prepared by lipase-catalysed hydrolysis using a short-chain acyl group, with E-values of up to 66 (ee up to 95%). 2-Phenylbutan-1-ol 1b was similarly resolved (up to 86% ee) using the optimised conditions, while the ester of the more sterically demanding 3-methyl-2-phenylbutan-1-ol 1c proved resistant to enzymatic hydrolysis under these conditions. Graphical abstract image
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A ceric ammonium nitrate based oxidative cleavage pathway for the asymmetric aldol adducts of oxadiazinones derived from (1R,2S)-N-p-methoxybenzylnorephedrine ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Austin R. Leise, Nicole Comas, Doug Harrison, Dipak Patel, Eileen G. Whitemiller, Jennifer Wilson, Jacob Timms, Ian Golightly, Christopher G. Hamaker, Shawn R. Hitchcock An N 4-p-methoxybenzyloxadiazinone has been prepared from (1R,2S)-norephedrine through a process of reductive amination, N-nitrosation, reduction, and cyclization. The oxadiazinone was acylated and employed in the asymmetric aldol addition reaction with aromatic and aliphatic aldehydes to yield aldol adducts in isolated yields ranging from 54% to 90%. Selected aldol adducts were treated with ceric ammonium nitrate in aqueous acetonitrile to afford the desired β-hydroxycarboxylic acids through a tandem process of oxidative cleavage of the N 4-p-methoxybenzyl group and acidic hydrolysis of the N 3-acyl side chain. The β-hydroxycarboxylic acids were recovered in high diastereomeric purity as determined by 500MHz 1H NMR spectroscopy and the absolute configuration was confirmed by polarimetry. The chiral auxiliary unit, the 3,4,5,6-tetrahydro-2H-1,3,4-oxadiazin-2-one (oxadiazinone), was converted into its corresponding 3,6-dihydro-2H-1,3,4-oxadiazin-2-one (oxadiazinone) through an oxidative pathway promoted by the ceric ammonium nitrate. Graphical abstract image
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Reaction of (S)-homoserine lactone with Grignard reagents: synthesis of amino-keto-alcohols and β-amino acid derivatives ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Özlem Gündoğdu, Pınar Turhan, Aytekin Köse, Ramazan Altundaş, Yunus Kara The ring-opening reaction of homoserine lactone with phenylmagnesium bromides was systematically examined. A reliable method to achieve β-amino acid precursors was developed by tuning the reaction conditions to favor mono-addition to the carbonyl moiety of the lactone. Graphical abstract image
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Enzymatic kinetic resolution of Morita-Baylis-Hillman acetates ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Wanyama P. Juma, Varsha Chhiba, Dean Brady, Moira L. Bode Racemic Morita-Baylis-Hillman adducts derived from the reaction of acrylonitrile with benzaldehyde, cinnamaldehyde and hydrocinnamaldehyde have been successfully resolved by means of enzymatic kinetic resolution. The (+)-alcohol products were isolated with 94–97% ee after lipase-mediated enantioselective hydrolysis of the corresponding acetates. Mosher’s double derivatisation protocol was applied to these isolated products and the absolute configuration of the alcohols was found to be (S) for all three substrates. Graphical abstract image
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Stereoselective synthesis and anticancer activity of broussonetine analogues ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Dominika Jacková, Miroslava Martinková, Jozef Gonda, Mária Vilková, Martina Bago Pilátová, Peter Takáč The stereoselective synthesis of two broussonetine analogues 14·HCl and ent-14·HCl with differing stereochemistry of the polyhydroxylated pyrrolidine core and a simple C13 alkyl fragment has been achieved. For their construction, the known oxazolidinones 15 and 16 were chosen as appropriate advanced scaffolds. The common hydrophobic side chain was incorporated at an early stage of the synthesis through Grubbs’ cross metathesis chemistry. The required pyrrolidine skeleton was then formed by the cyclization of open chain intermediates 17 and 18. Four synthesized compounds were screened in vitro for antiproliferative/cytotoxic activity against six cancer cell lines by MTT assay. Compounds 14·HCl (HeLa and A-549) and ent-14·HCl (Caco-2 and Jurkat) showed comparable or higher potency than conventional anticancer agent cisplatin on at least two evaluated cancer cells, respectively. Graphical abstract image
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Asymmetric synthesis of serinol-monoesters catalyzed by amine transaminases ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9 Author(s): Ingrid C.R. Costa, Rodrigo Octavio M.A. de Souza, Uwe T. Bornscheuer The asymmetric synthesis of serinol-derivatives was investigated employing different amine transaminases as biocatalysts. Under the optimized conditions conversions up to 92% and excellent enantiomeric excesses up to 99% ee were obtained providing access to both, the (R)- and (S)-configurations of the serinol-monoester (2-amino-3-hydroxypropyl hexanoate). Graphical abstract image
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Stereochemistry abstracts ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9
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Tetrahedron: Asymmetry Reports ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9
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Cumulative author index ()
Publication date: 15 September 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 9
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A question of policy: should tests for the self-disproportionation of enantiomers (SDE) be mandatory for reports involving scalemates? ()
Publication date: Available online 12 September 2017 Source:Tetrahedron: Asymmetry Author(s): Vadim A. Soloshonok, Alicja Wzorek, Karel D. Klika The self-disproportionation of enantiomers (SDE) is a phenomenon that can lead to the perturbation of the enantiomeric excess (ee) in fractions obtained from a scalemic sample that has been subjected to a physical process. While fractional crystallization is widely appreciated as a means to effect enantiopurification, processes that are potentially able to give rise to the SDE phenomenon, notably chromatography, are greatly underappreciated in this regard. In this exposition we question if sufficient care is being taken by workers to avoid the erroneous reporting of stereochemical outcomes in asymmetric synthesis, natural products work, and other chiral-based areas of study due to ignorance of the SDE phenomenon and recommend the incorporation of SDE tests via sublimation and achiral chromatography as outlined herein to check for the occurrence of the SDE phenomenon in the applied methodology and routine experimental work. Graphical abstract image
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‘Double chiral’ new members of calixsalen family ()
Publication date: Available online 7 September 2017 Source:Tetrahedron: Asymmetry Author(s): Małgorzata Petryk, Agnieszka Janiak, Marcin Kwit Synthesis and X-ray diffraction studies on the first examples of ‘double chiral’ calixsalens are presented. In these molecules, one can clearly distinguish two chiral zones. The first one is made by the macrocycle base, whereas the second chiral zone is set up of the additional chirality elements in the tail of the molecule. The ‘double chiral’ calixsalens are formed through cyclocondensation between chiral vicinal diamine of trans-1,2-diaminocyclohexane type and chiral C-5 substituted 2-hydroxyisophthalaldehyde derivatives. The absolute configuration of the dialdehyde did not affect the yield of the macrocyclization reaction. The presence of secondary amides in the tail part of the macrocycle leads to formation of hydrogen bonding network in the solid state, while sterical hindrance preserve interdigitation, thus, ‘double chiral’ calixsalens do not form aggregates typical for other calixsalens. Graphical abstract image
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Synthesis, crystal structure, and absolute configuration of the enantiomers of chiral drug xibenolol hydrochloride ()
Publication date: Available online 1 September 2017 Source:Tetrahedron: Asymmetry Author(s): Alexander A. Bredikhin, Zemfira A. Bredikhina, Alexey V. Kurenkov, Aidar T. Gubaidullin Based on the features of its crystallization, racemic 3-(2,3-dimethylphenoxy)propane-1,2-diol 2, the synthetic precursor of the chiral drug xibenolol 1, was resolved into pure enantiomers by the direct method of entrainment. The enantiomers of diol 2 through a Mitsunobu reaction were converted into the nonracemic 1,2-epoxy-3-(2,3-dimethylphenoxy)propanes (S)- and (R)-3, and then into the xibenolol enantiomers. Single crystals of (+)- and (−)-1·HCl were studied by X-ray diffraction. On the basis of the Flack parameter, the absolute (R)- and (S)-configurations were assigned to these compounds and to the other intermediate chiral substances. Graphical abstract image
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Determination of the absolute configuration of two αvβ6 integrin inhibitors for the treatment of idiopathic pulmonary fibrosis and investigations on the asymmetric 1,4-addition of arylboronic acids to crotonate esters bearing a C4-oxygen substituent ()
Publication date: Available online 31 August 2017 Source:Tetrahedron: Asymmetry Author(s): Panayiotis A. Procopiou, Tim N. Barrett, Royston C.B. Copley, Christopher J. Tame The absolute configuration of two novel αvβ6 integrin inhibitors was established via degradation to the corresponding C3-aryl substituted butyrolactone. The configuration of the resulting lactones was established by asymmetric synthesis using 1,4-addition of arylboronic acids to butenolide, catalysed by bis(norbornadiene)rhodium (I) tetrafluoroborate in the presence of (R)-BINAP, and confirmed by X-ray crystallography. Studies on arylboronic acid conjugate additions to acyclic crotonate esters bearing a γ-oxygen substituent are also reported. Three Rh catalysts were investigated and the one giving the highest enantioselectivity was bis(norbornadiene)rhodium (I) tetrafluoroborate. Graphical abstract image
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Dual chiral silver catalyst in the synthetic approach to the core of hepatitis C virus inhibitor GSK 625433 using enantioselective 1,3-dipolar cycloaddition of azomethine ylides and electrophilic alkenes ()
Publication date: Available online 30 August 2017 Source:Tetrahedron: Asymmetry Author(s): Ihssene Chabour, Luis M. Castelló, Juan Mancebo-Aracil, María Martín-Rodríguez, María de Gracia Retamosa, Carmen Nájera, José M. Sansano The asymmetric 1,3-dipolar cycloaddition of an imino ester 5 with tert-butyl acrylate is catalyzed by a dual chiral silver(I) complex formed from a chiral phosphoramidite 14 and the chiral silver(I) binolphosphate (R)-17. This reaction is selected to achieve the synthesis of enantiomerically enriched key structures to access the third generation of GSK HCV inhibitors. The scope of this dual chiral catalytic system is analyzed by employing different imino esters and dipolarophiles, and also compared with the same cycloaddition reactions performed with the chiral phosphoramidite 14·AgClO4 complex. Graphical abstract image
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An enantiopure diselenide based on a chiral bicyclic backbone—synthesis and configuration assignment ()
Publication date: Available online 30 August 2017 Source:Tetrahedron: Asymmetry Author(s): Karolina Kamińska, Elżbieta Wojaczyńska, Claudio Santi, Luca Sancineto, Marianna Francesca Pensa, Andrzej Kochel, Robert Wieczorek, Jacek Wojaczyński, Gauthier Slupski An enantiomerically pure diselenide containing two chiral bicyclic subunits was prepared from the respective halides. The stereochemical outcome of the reaction was established via NMR spectroscopy and X-ray diffraction measurements. Graphical abstract image
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Stereoselective allylation and reduction of N-tert-butanesulfinyl-α-keto aldimines ()
Publication date: Available online 23 August 2017 Source:Tetrahedron: Asymmetry Author(s): Edgar Maciá, Francisco Foubelo, Miguel Yus A simple methodology for the synthesis of N-tert-butanesulfinyl-α-keto aldimines from both α-keto aldehydes and carboxylic esters has been developed. The addition of an in situ formed allyl indium reagent to these chiral imines was also studied. The addition took place in a sequential manner, first to the imine group with excellent diastereoselectivity and then to the carbonyl group with lower diastereoselectivity. Ruthenium-catalyzed ring closing metathesis of the resulting 5-aminoocta-1,7-dien-4-ol derivatives provided access to 6-aminocyclohex-3-enols. Reduction of the α-keto aldimines led to N-tert-butanesulfinyl-1,2-aminoalcohols as a 1:1 diastereomeric mixture. Graphical abstract image
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Benzyl isobornyl amines: a simple and practical class of NMR discriminating agents for effective chiral recognition of acids ()
Publication date: Available online 23 August 2017 Source:Tetrahedron: Asymmetry Author(s): Jayaraman Kannappan, Aditya N. Khanvilkar, Gourav M. Upadhyay, Ashutosh V. Bedekar The design and synthesis of a few simple N-benzyl derivatives of isobornyl amine is presented. The derivatives have been assessed as chiral solvating agents for effective discrimination of the signals of some acids in NMR analysis. The single crystal X-ray analysis of the salts of (R)-mandelic acid with two of the title derivatives help to understand the supramolecular interactions and assign the induced chemical shifts in 1H NMR analysis. The title derivative is found to be suitable for quantitative determination of the enantiomeric excess of unknown enantiomeric purity as well as being efficient in resolving racemic mandelic acid. Graphical abstract image
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Editorial board ()
Publication date: 15 August 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 8
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Graphical contents list ()
Publication date: 15 August 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 8
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Contributors to this issue ()
Publication date: 15 August 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 8
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Applications of sharpless asymmetric dihydroxylation in the total synthesis of natural products ()
Publication date: 15 August 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 8 Author(s): Majid M. Heravi, Vahideh Zadsirjan, Maryam Esfandyari, Tahmineh Baie Lashaki Sharpless asymmetric dihydroxylation involves the reaction of an alkene with osmium tetroxide in the presence of a chiral quinine ligand to form an optically active vicinal diol. This reaction was primarily developed by Sharpless based on the already known racemic Upjohn dihydroxylation. The chiral diols obtained by Sharpless asymmetric dihydroxylation are important intermediates in organic synthesis. Herein, we emphasise the applications of Sharpless asymmetric dihydroxylation in the total synthesis of natural products. Graphical abstract image
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Asymmetric synthesis of spirocyclohexanone-pyrrolidine via AgI-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides ()
Publication date: 15 August 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 8 Author(s): Bilel Bdiri, Chuan Li, Zhi-Ming Zhou Cinchonine was effectively used in an AgOAc-catalysed asymmetric 1,3-dipolar cycloaddition of azomethine ylides with 2,6-bis(arylmethylidene) cyclohexanones, affording spiropyrrolidine derivatives with excellent yields (up to 99%), diastereoselectivities (up to 96:04 dr), and enantioselectivities (up to 99% ee). Graphical abstract image
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