A Crystal‐to‐Crystal Synthesis of Triazolyl‐Linked Polysaccharide

Pathigoolla, Atchutarao; Sureshan, Kana M.

doi:10.1002/ange.201303372

Cited by 26 publications

(4 citation statements)

References 60 publications

(20 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1,2,3‐triazole ring is well established as a bioisostere notably as an amide, carboxylic acid, and ester surrogates (Bonandi et al, 2017) Of note is that a sugar triazolyl nucleoside has been synthesized as a nucleoside triphosphate mimic and shown to be an ATP‐competitive inhibitor (Rowan et al, 2009). On the other hand, linear or cyclic 1,2,3‐triazole pseudo oligosaccharide have been reported but with the aim of obtaining new materials or to be used as scaffolds (Campo et al, 2015; Pathigoolla & Sureshan, 2013; Schmidt, Götz, Koch, Grimm, & Ringwald, 2016; Temelkoff, Zeller, & Norris, 2006). In one case, triazoles were used as mannose surrogates in the development of high mannose mimics but they most likely serve as spacers (François‐Heude et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Linear triazole‐linked pseudo oligogalactosides as scaffolds for galectin inhibitor development

et al. 2020

View full text Add to dashboard Cite

Galectins play key roles in numerous biological processes. Their mode of action depends on their localization which can be extracellular, cytoplasmic, or nuclear and is partly mediated through interactions with β‐galactose containing glycans. Galectins have emerged as novel therapeutic targets notably for the treatment of inflammatory disorders and cancers. This has stimulated the design of carbohydrate‐based inhibitors targeting the carbohydrate recognition domains (CRDs) of the galectins. Pursuing this approach, we reasoned that linear oligogalactosides obtained by straightforward iterative click chemistry could mimic poly‐lactosamine motifs expressed at eukaryote cell surfaces which the extracellular form of galectin‐3, a prominent member of the galectin family, specifically recognizes. Affinities toward galectin‐3 consistently increased with the length of the representative oligogalactosides but without reaching that of oligo‐lactosamines. Elucidation of the X‐ray crystal structures of the galectin‐3 CRD in complex with a synthesized di‐ and tri‐galactoside confirmed that the compounds bind within the carbohydrate‐binding site. The atomic structures revealed that binding interactions mainly occur with the galactose moiety at the non‐reducing end, primarily with subsites C and D of the CRD, differing from oligo‐lactosamine which bind more consistently across the whole groove formed by the five subsites (A‐E) of the galectin‐3 CRD.

show abstract

Section: Discussionmentioning

confidence: 99%

Linear triazole‐linked pseudo oligogalactosides as scaffolds for galectin inhibitor development

et al. 2020

View full text Add to dashboard Cite

show abstract

“…We have exploited the Topochemical Azide‐Alkyne Cycloaddition (TAAC) reaction for the successful synthesis of many crystalline polymers, [37] including mimics of polysaccharides, [38,39] proteins, [40–44] and nucleic acids [45] . We recently introduced the Topochemical Ene‐Azide Cycloaddition (TEAC) reaction, [46,47] which allows the synthesis of polymers whose backbone can be modified post‐synthetically via the denitrogenation of the triazoline ring formed in the cycloaddition reaction.…”

Section: Figurementioning

confidence: 99%

Massive Molecular Motion in Crystal Leads to an Unexpected Helical Covalent Polymer in a Solid‐state Polymerization

Khazeber,

Kana,

Sureshan

2024

Angew Chem Int Ed

Self Cite

View full text Add to dashboard Cite

We designed a proline‐derived monomer with azide and alkene functional groups to enable topochemical ene‐azide cycloaddition (TEAC) polymerization. In its crystal, the monomer forms supramolecular helices along the 'a' axis through various non‐covalent interactions. Along the 'c' axis, the molecules arrange themselves head‐to‐tail in a wave‐like pattern, positioning the azide and alkene groups of adjacent molecules in close proximity and anti‐parallel orientation, complying with Schmidt's criteria for topochemical reaction. This prearranged configuration was expected to facilitate smooth topochemical polymerization, resulting in a 1,4‐triazoline‐linked polymer. Upon heating, the monomer underwent TEAC polymerization in a remarkable single‐crystal‐to‐single‐crystal fashion, but, to our surprise, it yielded an unexpected covalent helical polymer linked by 1,5‐disubstituted triazoline units. Remarkably, the crystal avoids the ready‐to‐react arrangement for polymerization, but connects monomer molecules within the supramolecular helix through the cycloaddition of azide and alkene groups, even though they are not in close proximity nor in the expected orientation. This unexpected path, involving a substantial 134° rotation of the alkene group, yields hitherto unknown 1,5‐disubstituted triazoline product regiospecifically. This study serves as a cautionary reminder that relying solely on topochemical postulates for predicting reactivity can sometimes be misleading.

show abstract

“…Thus, in the direction perpendicular to the hydrogen-bonding direction, the molecules arrange in a head-to-tail fashion, preorganizing the reactive azide and alkyne groups ready for TAAC reaction. 31 In order to investigate this, we synthesized the galactose derivative 3. In its crystal structure, as expected, the hydroxyl groups at C2 and C3 formed a 1D zigzag hydrogen-bonded assembly of molecules (Figure 2c).…”

Section: Taac Reaction In Carbohydratesmentioning

confidence: 99%

Topochemical Azide–Alkyne Cycloaddition Reaction

Hema

Sureshan

2019

Acc. Chem. Res.

Self Cite

View full text Add to dashboard Cite

Conspectus Topochemical reactions are solid-state reactions that transpire under the strict control of molecular packing in the crystal lattice. Due to this lattice control, these reactions generate products in a regio-/stereospecific manner and in very high yields. In a broader sense, topochemical reactions mimic nature’s way of carrying out reactions in a confined environment of enzymes giving specific products. Apart from their remarkable specificity, topochemical reactions have many other interesting features that make these reactions more attractive than solution-phase reactions. Solution-phase reactions necessitate the use of reactants, reagents, catalysts, and solvents and often give products along with varying amounts of byproducts, necessitating complex workup and chromatographic purification using various chemicals. These inevitable chemical wastes from solution-state reactions could be avoided by topochemical reactions, as they are solvent-free and catalyst-free and often do not require any chromatographic purification in view of their specificity and high yielding nature. Also the confinement offered by the crystal lattice gives products that are not possible by solution-phase reactions. Another interesting feature of topochemical reactions is the possibility of formation of products in an ordered (crystalline) form, which imparts interesting properties. Thus, topochemical reactions have control not only at the molecular level (regio-/stereospecificity) but also at the supramolecular level (packing). Many topochemical reactions happen in single-crystal-to-single-crystal (SCSC) fashion, and crystal structure analysis of such reactions often gives mechanistic insights and knowledge about the geometrical criteria required for the reaction. Despite all these attractive features, reactions that can be done topochemically are limited. There is tremendous interest in the development of new categories of topochemical reactions and strategies to achieve reactivity in crystals. In this Account, we will summarize our attempts to develop topochemical azide–alkyne cycloaddition (TAAC) reactions. We have used hydrogen-bonding as the main noncovalent interaction for aligning azide-and-alkyne-substituted derivatives of various biomolecules in orientations suitable for their proximity-driven cycloaddition reaction in crystals. Overall, three major classes of biomolecules; carbohydrates, nucleosides, and peptides were successfully exploited for their TAAC reactions using conventional O–H···O, N–H···O, and N–H···N hydrogen bonds as supramolecular glues for controlling their assembly in crystals. The crystals of these monomers underwent TAAC reaction either spontaneously at room temperature or under heating yielding triazole-linked biopolymer mimics. The ordered packing of product molecules imparted special properties to the products formed. The legendary “cream of the crop” azide–alkyne click reaction has diverse applications in the areas of bioconjugation, material science, polymer synthesis, and so forth. Belonging to...

show abstract

A Crystal‐to‐Crystal Synthesis of Triazolyl‐Linked Polysaccharide

Abstract: Süße Kristalle: Die Synthese von Polysacchariden wird durch viele Faktoren erschwert. Die topochemische Azid‐Alkin‐Cycloadditionspolymerisation eines ungeschützten Monosaccharids umgeht diese Probleme und liefert regioselektiv ein kristallines Glycopolymer in quantitativer Ausbeute.

Cited by 26 publications

References 60 publications

Linear triazole‐linked pseudo oligogalactosides as scaffolds for galectin inhibitor development

Linear triazole‐linked pseudo oligogalactosides as scaffolds for galectin inhibitor development

Massive Molecular Motion in Crystal Leads to an Unexpected Helical Covalent Polymer in a Solid‐state Polymerization

Topochemical Azide–Alkyne Cycloaddition Reaction

Contact Info

Product

Resources

About