Acceptors In Reactions Research Articles

Reversible Chemical Reactivity of Non-Fullerene Acceptors for Organic Solar Cells under Acidic and Basic Environment

The chemical stability of non-fullerene acceptors under acidic and basic environments is important because the printable electrodes and interfacial layers are typically acidic (such as PEDOT:PSS) o...

Stereoselectivity in Glycosylation with Deoxofluorinated Glucosazide and Galactosazide Thiodonors.

Control of anomeric stereoselectivity in glycosylation with deoxofluorinated glycosyl donors is critical for assembly of fluorinated oligosaccharides. Here, we report the synthesis of benzylated 3-fluoro and 4-fluoro analogues of phenyl 1-thioglucosazide and galactosazide donors and evaluation of their stereoselectivity in glycosylation of a series of model carbohydrate acceptors using the Tf2O/Ph2SO promoter system. Low-temperature NMR revealed formation of covalent α-triflate and both anomers of oxosulfonium triflates under selected glycosylation conditions. This study demonstrates how the stereoselectivity depends on acceptor reactivity and glycosyl donor configuration. Reactive acceptors favor formation of 1,2- trans-β-glycosides with both d- gluco and d- galacto donors, whereas poorly reactive acceptors favor formation of 1,2- cis-α-glycosides with d- galacto donors but are unselective with d- gluco donors.

Evolution of folate biosynthesis and metabolism across algae and land plant lineages

Tetrahydrofolate and its derivatives, commonly known as folates, are essential for almost all living organisms. Besides acting as one-carbon donors and acceptors in reactions producing various important biomolecules such as nucleic and amino acids, as well as pantothenate, they also supply one-carbon units for methylation reactions. Plants along with bacteria, yeast and fungi synthesize folates de novo and therefore constitute a very important dietary source of folates for animals. All the major steps of folate biosynthesis and metabolism have been identified but only few have been genetically characterized in a handful of model plant species. The possible differences in the folate pathway between various plant and algal species have never been explored. In this study we present a comprehensive comparative study of folate biosynthesis and metabolism of all major land plant lineages as well as green and red algae. The study identifies new features of plant folate metabolism that might open new directions to folate research in plants.

Reaction of Sodium Nitroprusside and Potassium Dichromate on Benzaldehyde Di N-Butyl Acetal

The reaction of benzaldehyde di n-butyl acetal catalyzed by halomethanes in contrast to those catalyzed by Lewis acids, n-halocompounds, etc., has received only a little attention. Aliphatic acetal gives benzaldehyde and butyl benzoate as the main products. This reaction features induced the authors to take up the title investigations. Halomethanes are synthetically very useful reagents and vary widely in their acceptor synthon character and reactivity, hence their applications in the present work.

Acceptor reactivity in glycosylation reactions.

The outcome of a glycosylation reaction critically depends on the reactivity of all reaction partners involved: the donor glycoside (the electrophile), the activator (that generally provides the leaving group on the activated donor species) and the glycosyl acceptor (the nucleophile). The influence of the donor on the outcome of a glycosylation reaction is well appreciated and documented. Differences in donor reactivity have led to the development of chemoselective glycosylation reactions and the reactivity of donor glycosides has been tuned to affect stereoselective glycosylation reactions. The quantification of donor reactivity has enabled the conception of streamlined one-pot glycosylation sequences. In contrast, although it has long been known that the nature and the reactivity of the nucleophile influence the outcome of a glycosylation, the knowledge of acceptor reactivity and insight into the consequences thereof are often circumstantial or anecdotal. This review documents how the reactivity impacts the glycosylation reaction outcome both in terms of chemical yield and stereoselectivity. The effect of acceptor nucleophilicity on the reaction mechanism is described and steric, conformational and electronic influences are outlined. Quantitative and computational approaches to comprehend acceptor nucleophilicity are assessed. The increasing insight into the stereoelectronic effects governing glycoside reactivity will eventually enable the conception of effective stereoselective glycosylation methodology that can be tuned to the reaction partners at hand.

Metallophilic Mercuraazamacrocycles Derived from Bis{6‐formyl‐(2,3,4‐trimethoxy)phenyl}mercury: Reactivity with d10and d8Metal Ions

A (2+2) Dipodal condensation of bis{6‐formyl‐(2,3,4‐trimethoxy)phenyl}mercury (14) with various 1,2‐disubstitued diamines e.g., ethylenediamine,trans‐1,2‐diaminocyclohexane ando‐phenylenediamine led to the formation of 22‐membered mercuraazametallamacrocycles, [Hg‐{1‐C6H‐2,3,4‐(OCH3)3‐6‐(CHN)}2‐CH2–CH2]2(15), [Hg‐{1‐C6H‐2,3,4‐(OCH3)3‐6‐(CHN)}2‐C6H10]2(16) and [Hg‐{1‐C6H‐2,3,4‐(OCH3)3‐6‐(CHN)}2‐C6H4]2(17) respectively. The acceptor abilities and reactivities of the macrocycles are compared with the corresponding 22‐membered mercuraazametallamacrocycles obtained from the condensation of bis(formylphenyl)mercury (12) with the diamines. Also attempts have been made to prepare macrocycles with functionalized aryldiamines. Orange colored CuIcomplexes,24([15·Cu]ClO4) and26([16·Cu]ClO4), were obtained upon the treatment of [Cu(CH3CN)4ClO4] with macrocycles15and16, respectively. Similarly, brown colored AgIcomplexes,25([15·Ag]ClO4), and27([16·Ag]ClO4) were isolated by reacting macrocycles15and16with AgClO4. The reaction of macrocycle15with equimolar Pt(COD)Cl2afforded cyclometalated platinum(II) complex, Pt‐{1‐C6H‐2,3,4‐(OCH3)3‐6‐(CHN‐CH2)}2(28). Bis(2‐amino‐5‐methylphenyl)mercury (23), shows a very strong intermolecular Hg···Hg interaction. Density functional theory calculations and atoms in molecules analysis revealed the presence of metallophilic d10···d10interactions as well as d10···d8interactions in the synthesized compounds.

Investigations of alkynylbenziodoxole derivatives for radical alkynylations in photoredox catalysis.

The alkynylbenziodoxole derivatives are recently developed alkynylation reagents in organic synthesis, which demonstrate excellent radical alkynylation reactivity in photoredox catalysis reactions. Herein we report the synthesis of alkynylbenziodoxole derivatives with difluoro, monofluoro, monomethoxy, and dimethoxy substitution on the benziodoxole moiety, and investigated their radical alkynylation reactivity for the first time. A series of mechanistic experiments were conducted to study the radical acceptor and oxidative quencher reactivity of alkynylbenziodoxoles, in which unsubstituted alkynylbenziodoxoles played balancing roles in both processes, while electron-rich benziodoxole derivatives demonstrate synthetic advantages in some cases.

Cover Picture: Mapping the Relationship between Glycosyl Acceptor Reactivity and Glycosylation Stereoselectivity (Angew. Chem. Int. Ed. 27/2018)

Cover Picture: Mapping the Relationship between Glycosyl Acceptor Reactivity and Glycosylation Stereoselectivity (Angew. Chem. Int. Ed. 27/2018)

Mapping the Relationship between Glycosyl Acceptor Reactivity and Glycosylation Stereoselectivity.

The reactivity of both coupling partners—the glycosyl donor and acceptor—is decisive for the outcome of a glycosylation reaction, in terms of both yield and stereoselectivity. Where the reactivity of glycosyl donors is well understood and can be controlled through manipulation of the functional/protecting‐group pattern, the reactivity of glycosyl acceptor alcohols is poorly understood. We here present an operationally simple system to gauge glycosyl acceptor reactivity, which employs two conformationally locked donors with stereoselectivity that critically depends on the reactivity of the nucleophile. A wide array of acceptors was screened and their structure–reactivity/stereoselectivity relationships established. By systematically varying the protecting groups, the reactivity of glycosyl acceptors can be adjusted to attain stereoselective cis‐glucosylations.

Mapping the Relationship between Glycosyl Acceptor Reactivity and Glycosylation Stereoselectivity

AbstractThe reactivity of both coupling partners—the glycosyl donor and acceptor—is decisive for the outcome of a glycosylation reaction, in terms of both yield and stereoselectivity. Where the reactivity of glycosyl donors is well understood and can be controlled through manipulation of the functional/protecting‐group pattern, the reactivity of glycosyl acceptor alcohols is poorly understood. We here present an operationally simple system to gauge glycosyl acceptor reactivity, which employs two conformationally locked donors with stereoselectivity that critically depends on the reactivity of the nucleophile. A wide array of acceptors was screened and their structure–reactivity/stereoselectivity relationships established. By systematically varying the protecting groups, the reactivity of glycosyl acceptors can be adjusted to attain stereoselective cis‐glucosylations.

Catalyst‐Enabled Site‐Divergent Stereoselective Michael Reactions: Overriding Intrinsic Reactivity of Enynyl Carbonyl Acceptors

AbstractA site‐divergent stereoselective Michael reaction system is developed based on the identification of two distinct catalysts. Cinchonidine‐derived thiourea catalyzes the 1,4‐addition of prochiral azlactone enolates to enynyl N‐acyl pyrazoles in a highly diastereo‐ and enantioselective manner to give stereochemically defined alkynes, while P‐spiro chiral triaminoiminophosphorane catalytically controls the stereoselective 1,6‐addition and the consecutive γ‐protonation of the vinylogous enolate intermediate to afford Z,E‐configured conjugated dienes. This 1,6‐adduct serves as a valuable precursor for the synthesis of a 2‐amino‐2‐deoxy sugar.

Catalyst-Enabled Site-Divergent Stereoselective Michael Reactions: Overriding Intrinsic Reactivity of Enynyl Carbonyl Acceptors.

A site-divergent stereoselective Michael reaction system is developed based on the identification of two distinct catalysts. Cinchonidine-derived thiourea catalyzes the 1,4-addition of prochiral azlactone enolates to enynyl N-acyl pyrazoles in a highly diastereo- and enantioselective manner to give stereochemically defined alkynes, while P-spiro chiral triaminoiminophosphorane catalytically controls the stereoselective 1,6-addition and the consecutive γ-protonation of the vinylogous enolate intermediate to afford Z,E-configured conjugated dienes. This 1,6-adduct serves as a valuable precursor for the synthesis of a 2-amino-2-deoxy sugar.

Quinocidin, a Cytotoxic Antibiotic with an Unusual 3,4-Dihydroquinolizinium Ring and Michael Acceptor Reactivity toward Thiols.

Cytotoxicity-guided fractionation of the culture broth of Actinomadura sp. TP-A0019 led to the isolation of quinocidin (1), a cytotoxic antibiotic with an unusual 3,4-dihydroquinolizinium ring. The structural assignment was made on the basis of high-field NMR experiments and chemical synthesis. Comparison of the spectral properties of 1 with those of its synthetic counterparts revealed that 1 is a racemic mixture of two enantiomers, which showed similar cytotoxicity against HeLa-S3 cells. Nucleophile-trapping experiments demonstrated that 1 captured 2-mercaptoethanol and N-acetyl-l-cysteine by means of a Michael addition-type reaction, but was inert toward 2-aminoethanol and glycolic acid. Notably, the addition of 1 to thiols proceeded smoothly in neutral aqueous media at room temperature. In view of the thiol-trapping ability and the unusual structure, 1 provides a unique scaffold for designing drug leads and protein-labeling probes.

Structure-Reactivity Relationships of Conformationally Armed Disaccharide Donors and Their Use in the Synthesis of a Hexasaccharide Related to the Capsular Polysaccharide from Streptococcus pneumoniae Type 37.

To advance the field of glycobiology, efficient synthesis methods of oligosaccharides and glycoconjugates are a requisite. In glycosylation reactions using superarmed donors, both selectivity and reactivity issues must be considered, and we herein investigate these aspects for differently protected β-linked 2-O-glycosylated glucosyl donors carrying bulky tert-butyldimethylsilyl groups to different extents. The acceptors in reactions being secondary alcohols presents a challenging situation with respect to steric crowding. Conformational pyranose ring equilibria of the superarmed disaccharide donors with axial-rich substituents contained skew and boat conformations, and three-state models were generally assumed. With NIS/TfOH as the promotor, 2,6-di-tert-butyl-4-methylpyridine as the base, and a dichloromethane/toluene solvent mixture, ethyl 1-thio-β-d-glucosyl disaccharide donors having 6-O-benzyl group(s) besides tert-butyldimethylsilyl groups were efficiently coupled at -40 °C to the hydroxyl group at position 3 of glucopyranosyl acceptors to form β-(1 → 2),β-(1 → 3)-linked trisaccharides, isolated in excellent 95% yield. The more axial-rich donors in skew and boat conformations are thus preorganized closer to the assumed transition state in these glycosylation reactions. The developed methodology was subsequently applied in the synthesis of a multibranched hexasaccharide related to the capsular polysaccharide from Streptococcus pneumoniae type 37, which consists of a β-(1 → 3)-linked backbone and a β-(1 → 2)-linked side chain of d-glucosyl residues in disaccharide repeating units.

Synthesis of 4,4-Disubstituted 3-Methylidenechroman-2-ones as Potent Anticancer Agents.

The synthesis of a new library of 4,4-disubstituted 3-methylidene-3,4-dihydro-2H-chroman-2-ones applying Horner-Wadsworth-Emmons methodology for the construction of an exo-methylidene moiety is reported. Corresponding 3-diethoxyphosphorylchroman-2-ones were synthesized in a three-step reaction sequence consisting of O-methylation of ethyl 2-diethoxyphosphoryl-3-oxoalkanoates, followed by reaction of the obtained 2-diethoxyphosphoryl-3-methoxy-2-alkenoates with phenols or 1-naphthol. The resulting 3-diethoxyphosphorylochromen-2-ones proved to be effective Michael acceptors in reactions with various Grignard reagents. Preliminary biological evaluations showed that many of the synthesized 3-methylidenechroman-2-ones possess very high cytotoxic activity against NALM-6 and HL-60 cancer cell lines (IC50 <1.0 μm) as well as high activity against the MCF-7 cancer cell line (IC50 <10 μm). Furthermore, two of the highly active 3-methylidenechroman-2-ones with geminal methyl and ethyl substituents at position 4 showed promising therapeutic indexes of 10 and 13 in tests against human umbilical vein endothelial cells (HUVECs).

Mapping the Reactivity and Selectivity of 2-Azidofucosyl Donors for the Assembly of N-Acetylfucosamine-Containing Bacterial Oligosaccharides.

The synthesis of complex oligosaccharides is often hindered by a lack of knowledge on the reactivity and selectivity of their constituent building blocks. We investigated the reactivity and selectivity of 2-azidofucosyl (FucN3) donors, valuable synthons in the synthesis of 2-acetamido-2-deoxyfucose (FucNAc) containing oligosaccharides. Six FucN3 donors, bearing benzyl, benzoyl, or tert-butyldimethylsilyl protecting groups at the C3-O and C4-O positions, were synthesized, and their reactivity was assessed in a series of glycosylations using acceptors of varying nucleophilicity and size. It was found that more reactive nucleophiles and electron-withdrawing benzoyl groups on the donor favor the formation of β-glycosides, while poorly reactive nucleophiles and electron-donating protecting groups on the donor favor α-glycosidic bond formation. Low-temperature NMR activation studies of Bn- and Bz-protected donors revealed the formation of covalent FucN3 triflates and oxosulfonium triflates. From these results, a mechanistic explanation is offered in which more reactive acceptors preferentially react via an SN2-like pathway, while less reactive acceptors react via an SN1-like pathway. The knowledge obtained in this reactivity study was then applied in the construction of α-FucN3 linkages relevant to bacterial saccharides. Finally, a modular synthesis of the Staphylococcus aureus type 5 capsular polysaccharide repeating unit, a trisaccharide consisting of two FucNAc units, is described.

Organo- and Organometallic-Catalytic Intramolecular [1,5]-Hydride Transfer/Cyclization Process through C(sp(3) )-H Bond Activation.

The direct functionalization of C(sp(3) )-H bonds is one of the most synthetically powerful research areas in current organic synthesis. Organocatalytic C(sp(3) )-H bond activation reactions have recently been developed in addition to the traditional metal-catalyzed C(sp(3) )-H activation reactions. In this review, we aim to give a brief overview of organo- and organometallic internal redox cascade reactions with respect to the mechanism, the reactivity of hydrogen donors and acceptors, and the migration modes of hydrogen.

Phenyl 2-azido-2-deoxy-1-selenogalactosides: a single type of glycosyl donor for the highly stereoselective synthesis of α- and β-2-azido-2-deoxy-d-galactopyranosides

Efficient glycosylation with phenyl 2-azido-2-deoxy-1-seleno-α-d-galactosides of glycosyl acceptors with different reactivities has been developed. The reaction provided glycosides of 2-azido-2-deoxy-d-galactose in good to high yields. The stereochemical outcome of the glycosylation of reactive acceptors (3-trifluoroacetamidopropanol and methyl 2,3-O-isopropylidene-α-l-rhamnopyranoside) can be broadly varied from complete β- to high α-selectivity by changing the reaction solvent, promoter and protecting groups in the donor, while the glycosylation of less reactive allyl 2,2′,3,3′,6,6′-hexa-O-benzoyl-β-lactoside afforded the corresponding α-glycosides exclusively.

Chemical Synthesis of a Glycopeptide Derived from Skp1 for Probing Protein Specific Glycosylation.

Skp1 is a cytoplasmic and nuclear protein, best known as an adaptor of the SCF family of E3-ubiquitin ligases that label proteins for their degradation. Skp1 in Dictyostelium is posttranslationally modified on a specific hydroxyproline (Hyp) residue by a pentasaccharide, which consists of a Fucα1,2-Galβ-1,3-GlcNAcα core, decorated with two α-linked Gal residues. A glycopeptide derived form Skp1 was prepared to characterize the α-galactosyltransferase (AgtA) that mediates the addition of the α-Gal moieties, and to develop antibodies suitable for tracking the trisaccharide isoform of Skp1 in cells. A strategy was developed for the synthesis of the core trisaccharide-Hyp based on the use of 2-naphthylmethyl (Nap) ethers as permanent protecting groups to allow late stage installation of the Hyp moiety. Tuning of glycosyl donor and acceptor reactivities was critical for achieving high yields and anomeric selectivities of glycosylations. The trisaccharide-Hyp moiety was employed for the preparation of the glycopeptide using microwave-assisted solid phase peptide synthesis. Enzyme kinetic studies revealed that trisaccharide-Hyp and trisaccharide-peptide are poorly recognized by AgtA, indicating the importance of context provided by the native Skp1 protein for engagement with the active site. The trisaccharide-peptide was a potent immunogen capable of generating a rabbit antiserum that was highly selective toward the trisaccharide isoform of full-length Skp1.

Acceptor Reactivity in the Total Synthesis of Alginate Fragments Containing α‐L‐Guluronic Acid and β‐D‐Mannuronic Acid

The total synthesis of mixed-sequence alginate oligosaccharides, featuring both β-D-mannuronic acid (M) and α-L-guluronic acid (G), is reported for the first time. A set of GM, GMG, GMGM, GMGMG, GMGMGM, GMGMGMG, and GMGGMG alginates was assembled using GM building blocks, having a guluronic acid acceptor part and a mannuronic acid donor side to allow the fully stereoselective construction of the cis-glycosidic linkages. It was found that the nature of the reducing-end anomeric center, which is ten atoms away from the reacting alcohol group in the key disaccharide acceptor, had a tremendous effect on the efficiency with which the building blocks were united. This chiral center determines the overall shape of the acceptor and it is revealed that the conformational flexibility of the acceptor is an all-important factor in determining the outcome of a glycosylation reaction.