Highly Strained Unsaturated Carbocycles

Zanda, Matteo; Bucci, Raffaella; Sloan, Nikki L.; Topping, Lydia

doi:10.1002/ejoc.202000512

Cited by 10 publications

(10 citation statements)

References 138 publications

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“…Flash chromatography was performed using silica gel (60 Å, particle size 40-63 μm) purchased from Merck. 1 H NMR and 13 C NMR spectra were recorded on a Bruker AVANCE III 400 NMR spectrometer and calibrated using residual non-deuterated solvent as internal reference. Chemical shifts (δ) are reported in parts per million (ppm) and coupling constants (J) are given in Hertz (Hz).…”

Section: Methodsmentioning

confidence: 99%

“…See the separate compounds for follow-up purification strategy. [1,2,3]triazol-1-yl)ethoxy)ethoxy)ethoxy)ethan-1ol (3a). Filtration through a pad of silica gel (n-Hex/Ac 2 O 1:1).…”

Section: Methodsmentioning

confidence: 99%

“…Rf = 0.24 (n-Hex/Ac 2 O 1:1). 1 and cultured for another ~ 2 hours to ensure the bacteria were in the logarithmic phase. Then, 2 aliquots of 1 mL (at a bacterial concentration of a million microliter) were spun down at 3000 g and suspended in 0.5 mL PBS (pH 7.4) or 0.5 mL of compound 8a in PBS (1 mg/mL, pH 7.4) for 1 h 30 min.…”

Section: Methodsmentioning

confidence: 99%

“…Reactions that proceed efficiently in biological systems are witnessing widespread applications in the fields of chemistry, chemical biology, material sciences and molecular diagnostics, where they enable manipulation of biomolecules, cells and particles and their tracking in vitro and in vivo. 1 Pioneered by Bertozzi's Staudinger ligation, 2 several bioorthogonal reactions were subsequently designed and developed. These reactions include the strain-promoted azide-alkyne cycloaddition (SPAAC) and the inverse electron-demand Diels-Alder (IEDDA) reaction.…”

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, Conjugation, and Reactivity of Novel trans,trans-1,5-Cyclooctadiene-Derived Bioorthogonal Linkers

et al. 2020

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The tetrazine/trans-cyclooctene (TCO) inverse electron-demand Diels−Alder (IEDDA) reaction is the fastest bioorthogonal "click" ligation process reported to date. In this context, TCO reagents have found widespread applications; however, their availability and structural diversity is still somewhat limited due to challenges connected with their synthesis and structural modification. To address this issue, we developed a novel strategy for the conjugation of TCO derivatives to a biomolecule, which allows for the creation of greater structural diversity from a single precursor molecule, i.e., trans,trans-1,5-cyclooctadiene [(E,E)-COD] 1, whose preparation requires standard laboratory equipment and readily available reagents. This two-step strategy relies on the use of new bifunctional TCO linkers (5a−11a) for IEDDA reactions, which can be synthesized via 1,3-dipolar cycloaddition of (E,E)-COD 1 with different azido spacers (5−11) carrying an electrophilic function (NHS-ester, N-succinimidyl carbonate, pnitrophenyl-carbonate, maleimide) in the ω-position. Following bioconjugation of these electrophilic linkers to the nucleophilic residue (cysteine or lysine) of a protein (step 1), the resulting TCO-decorated constructs can be subjected to a IEDDA reaction with tetrazines functionalized with fluorescent or near-infrared (NIR) tags (step 2). We successfully used this strategy to label bovine serum albumin with the TCO linker 8a and subsequently reacted it in a cell lysate with the fluorescein-isothiocyanate (FITC)derived tetrazine 12. The same strategy was then used to label the bacterial wall of Gram-positive Staphylococcus aureus, showing the potential of these linkers for live-cell imaging. Finally, we determined the impact of structural differences of the linkers upon the stability of the bioorthogonal constructs. The compounds for stability studies were prepared by conjugation of TCO linkers 6a, 8a, and 10a to mAbs, such as Rituximab and Obinutuzumab, and subsequent labeling with a reactive Cy3-functionalized tetrazine.

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Section: Methodsmentioning

confidence: 99%

“…See the separate compounds for follow-up purification strategy. [1,2,3]triazol-1-yl)ethoxy)ethoxy)ethoxy)ethan-1ol (3a). Filtration through a pad of silica gel (n-Hex/Ac 2 O 1:1).…”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Design, Synthesis, Conjugation, and Reactivity of Novel trans,trans-1,5-Cyclooctadiene-Derived Bioorthogonal Linkers

et al. 2020

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“…Cyclopropane is particularly useful in the development of peptidomimetics, as it can fix its substituents into the trans-or cis-configuration, due its constrain. [41] This behavior is called 'cyclopropylic strain'. [42] In 2013, Mizuno et al reported on the stereoselective synthesis of cyclopropane based tetrapeptide mimics 47-50 (Figure 8), able to stabilize conformations covering β-turn through β-strand, depending on the chirality of the mimic.…”

Section: And 4-membered Ringsmentioning

confidence: 99%

Fishing in the Toolbox of Cyclic Turn Mimics: a Literature Overview of the Last Decade

et al. 2021

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Dedicated to Prof. Franco Cozzi for its 70th birthday.The main goal in developing peptidomimetics is the stabilization of the bioactive conformation of peptides. Among all the secondary structures, turns are of paramount importance. This review highlights the recent advances in the design and synthesis of cyclic turn mimics. Both amino acids, carbo-and hetero-cyclic scaffolds have been considered, focusing on their use in the preparation of peptidomimetics and on their ability to induce γ-, β-, and α-turns.

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