scholarly journals New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

2019 ◽  
Vol 15 ◽  
pp. 830-839
Author(s):  
Iveta Chena Tichá ◽  
Simona Hybelbauerová ◽  
Jindřich Jindřich
Keyword(s):  
Click Reaction ◽  
Enantiomeric Excess ◽  
Cinchona Alkaloids ◽  
Cinchona Alkaloid ◽  
Cyclodextrin Derivatives ◽  
Allylic Amination ◽  
Asymmetric Syntheses ◽  
Wide Range ◽  
Enantioselective Reactions ◽  
Organocatalytic Reactions

The preparation of new organocatalysts for asymmetric syntheses has become a key stage of enantioselective catalysis. In particular, the development of new cyclodextrin (CD)-based organocatalysts allowed to perform enantioselective reactions in water and to recycle catalysts. However, only a limited number of organocatalytic moieties and functional groups have been attached to CD scaffolds so far. Cinchona alkaloids are commonly used to catalyze a wide range of enantioselective reactions. Thus, in this study, we report the preparation of new α- and β-CD derivatives monosubstituted with cinchona alkaloids (cinchonine, cinchonidine, quinine and quinidine) on the primary rim through a CuAAC click reaction. Subsequently, permethylated analogs of these cinchona alkaloid–CD derivatives also were synthesized and the catalytic activity of all derivatives was evaluated in several enantioselective reactions, specifically in the asymmetric allylic amination (AAA), which showed a promising enantiomeric excess of up to 75% ee. Furthermore, a new disubstituted α-CD catalyst was prepared as a pure AD regioisomer and also tested in the AAA. Our results indicate that (i) the cinchona alkaloid moiety can be successfully attached to CD scaffolds through a CuAAC reaction, (ii) the permethylated cinchona alkaloid–CD catalysts showed better results than the non-methylated CDs analogues in the AAA reaction, (iii) promising enantiomeric excesses are achieved, and (iv) the disubstituted CD derivatives performed similarly to monosubstituted CDs. Therefore, these new CD derivatives with cinchona alkaloids effectively catalyze asymmetric allylic aminations and have the potential to be successfully applied in other enantioselective reactions.

Highly enantioselective asymmetric Henry reaction catalyzed by novel chiral phase transfer catalysts derived from cinchona alkaloids

2016 ◽  
Vol 14 (42) ◽  
pp. 10101-10109 ◽  
Author(s):  
Ponmuthu Kottala Vijaya ◽  
Sepperumal Murugesan ◽  
Ayyanar Siva
Keyword(s):  
Phase Transfer ◽  
Enantiomeric Excess ◽  
Cinchona Alkaloids ◽  
Henry Reaction ◽  
Reaction Conditions ◽  
Chiral Phase ◽  
Phase Transfer Catalysts ◽  
Wide Range ◽  
Chiral Phase Transfer Catalysts

Newly synthesized CPTCs are applied in the asymmetric Henry reaction to a wide range of aldehydes under mild reaction conditions, and we obtained higher chemical yields and an excellent enantiomeric excess.

scholarly journals Directed Evolution of Aptamer Discovery Technologies

2021 ◽  
Author(s):  
Diana Wu ◽  
Chelsea Gordon ◽  
John Shin ◽  
Michael Eisenstein ◽  
Hyongsok Tom Soh
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Click Reaction ◽  
Clinical Diagnostics ◽  
High Quality ◽  
Affinity Reagents ◽  
Wide Range ◽  
Target Binding ◽  
Modified Nucleobases ◽  
Parallel Fashion

Although antibodies are a powerful tool for molecular biology and clinical diagnostics, there are many emerging applications for which nucleic acid-based aptamers can be advantageous. However, generating high-quality aptamers with sufficient affinity and specificity for biomedical applications is a challenging feat for most research laboratories. In this Account, we describe four techniques developed in our lab to accelerate the discovery of high quality aptamer reagents that can achieve robust binding even for challenging molecular targets. The first method is particle display, in which we convert solution-phase aptamers into aptamer particles that can be screened via fluorescence-activated cell sorting (FACS) to quantitatively isolate individual aptamer particles based on their affinity. This enables the efficient isolation of high-affinity aptamers in fewer selection rounds than conventional methods, thereby minimizing selection biases and reducing the emergence of artifacts in the final aptamer pool. We subsequently developed the multi-parametric particle display (MPPD) method, which employs two-color FACS to isolate aptamer particles based on both affinity and specificity, yielding aptamers that exhibit excellent target binding even in complex matrices like serum. The third method is a click chemistry-based particle display (click-PD) that enables the generation and high-throughput screening of non-nattural aptamers with a wide range of base modifications. We have shown that these base-modified aptamers can achieve robust affinity and specificity for targets that have proven challenging or inaccessible with natural nucleotide-based aptamer libraries. Lastly, we describe the non-natural aptamer array (N2A2) platform, in which a modified benchtop sequencing instrument is used to characterize base-modified aptamers in a massively parallel fashion, enabling the efficient identification of molecules with excellent affinity and specificity for their targets. This system first generates aptamer clusters on the flow-cell surface that incorporate alkyne-modified nucleobases, and then performs a click reaction to couple those nucleobases to an azide-modified chemical moiety. This yields a sequence-defined array of tens of millions of base-modified sequences, which can then be characterized in a high-throughput fashion. Collectively, we believe that these advancements are helping to make aptamer technology more accessible, efficient, and robust, thereby enabling the use of these affinity reagents for a wider range of molecular recognition and detection-based applications.

Cinchona Alkaloid-Silyl Ether Derivatives as Organocatalysts for Asymmetric “Interrupted” Feist-Bénary Reaction

2013 ◽  
Vol 864-867 ◽  
pp. 456-459
Author(s):  
Ying Jin ◽  
Sheng Chang ◽  
Tian Yi Zhang ◽  
Bo Feng
Keyword(s):  
Enantiomeric Excess ◽  
Cinchona Alkaloid ◽  
Silyl Ether ◽  
Ethyl Bromopyruvate

Four cinchona alkaloid-silyl ether derivatives have been used to catalyze the asymmetric “interrupted” Feist-Bénary reaction of ethyl bromopyruvate/substituted bromo-ketoesters and 1,3-Cyclohexadione. The corresponding hydroxydihydrofurans have been obtained in excellent yields (85-96%) with high enantiomeric excess (ee) values of up to 90%.

Modified cinchona alkaloid-catalysed enantioselective [4+4] annulations of cyclobutenones and 1-azadienes

2020 ◽  
Vol 56 (53) ◽  
pp. 7257-7260
Author(s):  
Bo Jiang ◽  
Wei Du ◽  
Ying-Chun Chen
Keyword(s):  
Cinchona Alkaloids ◽  
Cinchona Alkaloid

An asymmetric [4+4] annulation reaction between β-substituted cyclobutenones and diverse 1-azadienes is developed under the catalysis of modified cinchona alkaloids.

scholarly journals Asymmetric Mannich Reaction: Synthesis of Novel Chiral 5-(substituted aryl)-1,3,4-Thiadiazole Derivatives with Anti-Plant-Virus Potency

2019 ◽  
Vol 25 (1) ◽  
pp. 47-51 ◽  
Author(s):  
Song Bai ◽  
Yunying Zhu ◽  
Qin Wu
Keyword(s):  
Tobacco Mosaic Virus ◽  
Mosaic Virus ◽  
Mannich Reaction ◽  
Plant Virus ◽  
Enantiomeric Excess ◽  
Cinchona Alkaloid ◽  
Reaction Synthesis ◽  
Thiadiazole Derivatives

AbstractA series of novel chiral 5-(substituted aryl)-1,3,4-thiadiazole derivatives was synthesized in an enantioselective three-component Mannich reaction using cinchona alkaloid squaramide catalyst with excellent enantioselectivities (up to >99% enantiomeric excess (ee)). The bioassay results showed that these derivatives possessed good to excellent activities against tobacco mosaic virus (TMV).

scholarly journals Evaluation of Antibacterial and Anti-biofilm Activities of Cinchona Alkaloid Derivatives against Staphylococcus aureus

2012 ◽  
Vol 7 (9) ◽  
pp. 1934578X1200700 ◽  
Author(s):  
Malena E. Skogman ◽  
Janni Kujala ◽  
Igor Busygin ◽  
Reko Leino ◽  
Pia M. Vuorela ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Cinchona Alkaloids ◽  
Cinchona Alkaloid ◽  
Bacterial Biofilms ◽  
Planktonic Bacteria ◽  
Naturally Occurring ◽  
Resazurin Assay ◽  
Synthetic Derivative ◽  
Synthetic Derivatives

Bacterial biofilms are resistant to most of the commonly available antibacterial chemotherapies. Thus, an enormous need exists to meet the demands of effective anti-biofilm therapy. In this study, a small library of cinchona alkaloids, including the naturally occurring compounds cinchonidine and cinchonine, as well as various synthetic derivatives and analogues was screened for antibacterial and anti-biofilm activity against the Staphylococcus aureus biofilm producing strain ATCC 25923. Two methods were used to evaluate activity against biofilms, namely crystal violet staining to measure biomass and resazurin assay to measure biofilms viability. Cinchonidine was found to be inactive, whereas a synthetic derivative, 11-triphenylsilyl-10,11-dihydrocinchonidine (11-TPSCD), was effective against planktonic bacteria as well as in preventing biofilm formation at low micromolar concentrations. Higher concentrations were required to eradicate mature biofilms.

Enantioselective Allylic Amination of Morita-Baylis-Hillman Carbonates Catalysed by Modified Cinchona Alkaloids

2009 ◽  
Vol 2009 (33) ◽  
pp. 5804-5809 ◽  
Author(s):  
Shan-Jun Zhang ◽  
Hai-Lei Cui ◽  
Kun Jiang ◽  
Rui Li ◽  
Zhen-Yu Ding ◽  
...  
Keyword(s):  
Cinchona Alkaloids ◽  
Allylic Amination

Lipid Peptide Core Nanoparticles as Multivalent Vaccine Candidates against Streptococcus pyogenes

2012 ◽  
Vol 65 (1) ◽  
pp. 35 ◽  
Author(s):  
Mariusz Skwarczynski ◽  
Bibi Hamideh Parhiz ◽  
Fatemeh Soltani ◽  
Saranya Srinivasan ◽  
Khairul A. Kamaruzaman ◽  
...  
Keyword(s):  
Streptococcus Pyogenes ◽  
Subunit Vaccine ◽  
Click Reaction ◽  
Group A Streptococcus ◽  
Vaccine Candidates ◽  
Wide Range ◽  
Group A ◽  
Core Peptide ◽  
Aqueous Conditions ◽  
Peptide Core

Traditional vaccine approaches for Group A streptococcus (GAS) infection are inadequate owing to the host’s production of cross-reactive antibodies that recognize not only the bacteria but also human tissue. To overcome this problem a peptide subunit-based vaccine was proposed, which would incorporate only minimal non-cross reactive epitopes. However, special delivery systems/adjuvants were required because short peptides are not immunogenic. In this study we have incorporated two epitopes from two different GAS proteins into a lipid core peptide (LCP) self-adjuvanting delivery system to achieve better protection against a wide range of GAS serotypes. Multivalent and monovalent constructs were synthesized with the help of an azide alkyne cycloaddition (click) reaction and their ability to self-assemble under aqueous conditions was examined. The compounds significantly differed in their ability to form small size nanoparticles, which are believed to be most appropriate for peptide-based subunit vaccine delivery. The LCP conjugates possessing two different epitopes, in contrast to monoepitopic constructs, formed small nanoparticles (5–15 nm) presumably owing to a suitable hydrophilic-hydrophobic balance of the molecules.

Efficient general asymmetric syntheses of 3-substituted 1(3H)-isobenzofuranones in very high enantiomeric excess

1996 ◽  
Vol 37 (13) ◽  
pp. 2205-2208 ◽  
Author(s):  
P.Veeraraghavan Ramachandran ◽  
Guang-Ming Chen ◽  
Herbert C. Brown
Keyword(s):  
Enantiomeric Excess ◽  
Asymmetric Syntheses ◽  
Substituted 1 ◽  
Very High

Formation and Structure of Cinchona Alkaloid (Bis-2,3-naphthalenediyl)orthoborate Salts

2000 ◽  
Vol 55 (11) ◽  
pp. 1083-1088 ◽  
Author(s):  
Maciej Kubicki ◽  
Teresa Borowiak ◽  
Krystyna Gawrońska ◽  
Jacek Gawroński
Keyword(s):  
Crystal Structure ◽  
Nitrogen Atom ◽  
Hydrogen Bonds ◽  
Cinchona Alkaloids ◽  
Cinchona Alkaloid ◽  
Cd Spectra ◽  
Polar Solvents ◽  
X Ray ◽  
Solvent Molecules ◽  
Additional Hydrogen

A series of (bis-2,3-naphthalenediyl)orthoborate salts of Cinchona alkaloids has been synthesized and characterized. The interactions between ions in the salts have been studied by means of circular dichroism spectroscopy and X-ray crystal structure determination. The CD spectra of the dihydroquinidine salt show that in non-polar solvents it exists as a tightly held ion pair. The crystal structure of the cinchonidine salt proves the existence of ions in the solid state. The protonation takes place at the quinuclidine nitrogen atom. The hydrogen bonds connect cation and anion into one recognizable unit. Additional hydrogen bonds (with hydroxy group as a hydrogen donor and quinoline nitrogen atom as an acceptor) form infinite chains of cations along the [001] direction. There are cavities in the crystal structure that are partially filled by solvent molecules (acetone).

Sign in / Sign up

Export Citation Format

Share Document