Synthesis of NH‐Sulfoximines by Using Recyclable Hypervalent Iodine(III) Reagents under Aqueous Micellar Conditions

Zhang, Guocai; Tan, Hongsheng; Chen, Wei‐Chun; Shen, Hong C.; Lu, Yue; Zheng, Changwu; Hong, Xu

doi:10.1002/cssc.201903430

Cited by 26 publications

(20 citation statements)

References 92 publications

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“…(ii) Hydrogen-bonding to the oxygens is expected to deactivate the sulfinate obtained by ring-opening exchange as a nucleophile ( XIV , Figure 2 D). 66 In proteins, sulfinates are produced by the oxidation of cysteine thiols, but deactivated through hydrogen bonding, thus rarely exchanging with disulfides to form thiosulfonate bridges. 67 We therefore decided to surround CTOs by hydrophobic groups, which should direct CTOs into aprotic pockets of proteins or membranes to prevent such inactivation (e.g., Figure 2 C, XI , XII , blue circles, 2D, XV ).…”

Section: Resultsmentioning

confidence: 99%

Cyclic Thiosulfonates for Thiol-Mediated Uptake: Cascade Exchangers, Transporters, Inhibitors

Kato

Lim

Cheng

et al. 2022

JACS Au

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Thiol-mediated uptake is emerging as a powerful method to penetrate cells. Cyclic oligochalcogenides (COCs) have been identified as privileged scaffolds to enable and inhibit thiol-mediated uptake because they can act as dynamic covalent cascade exchangers, i.e., every exchange produces a new, covalently tethered exchanger. In this study, our focus is on the essentially unexplored COCs of higher oxidation levels. Quantitative characterization of the underlying dynamic covalent exchange cascades reveals that the initial ring opening of cyclic thiosulfonates (CTOs) proceeds at a high speed even at a low pH. The released sulfinates exchange with disulfides in aprotic but much less in protic environments. Hydrophobic domains were thus introduced to direct CTOs into hydrophobic pockets to enhance their reactivity. Equipped with such directing groups, fluorescently labeled CTOs entered the cytosol of living cells more efficiently than the popular asparagusic acid. Added as competitive agents, CTOs inhibit the uptake of various COC transporters and SARS-CoV-2 lentivectors. Orthogonal trends found with different transporters support the existence of multiple cellular partners to account for the diverse expressions of thiol-mediated uptake. Dominant self-inhibition and high activity of dimers imply selective and synergistic exchange in hydrophobic pockets as distinguishing characteristics of thiol-mediated uptake with CTOs. The best CTO dimers with hydrophobic directing groups inhibit the cellular entry of SARS-CoV-2 lentivectors with an IC 50 significantly lower than the previous best CTO, below the 10 μM threshold and better than ebselen. Taken together, these results identify CTOs as an intriguing motif for use in cytosolic delivery, as inhibitors of lentivector entry, and for the evolution of dynamic covalent networks in the broadest sense, with reactivity-based selectivity of cascade exchange emerging as a distinguishing characteristic that deserves further attention.

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Section: Resultsmentioning

confidence: 99%

Cyclic Thiosulfonates for Thiol-Mediated Uptake: Cascade Exchangers, Transporters, Inhibitors

Kato

Lim

Cheng

et al. 2022

JACS Au

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“…The simplicity of this procedure entailed a huge step in the popularization of sulfoximines. Its compatibility was already demonstrated with wide range of substrates, including thiophenes, [31] and different solvents [44] or amine sources [45] . Furthermore, the accessibility of sulfoximines enabled late stage functionalization on the imine nitrogen to give different properties [45–47] …”

Section: Figurementioning

confidence: 99%

Planarizable Push‐Pull Probes with Sulfoximine‐Bridged Dithienothiophene Acceptors

García‐Calvo

López‐Andarias

Sakai

et al. 2022

Helvetica Chimica Acta

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Contrary to sulfides, sulfoxides or sulfones, sulfoximines have been mostly neglected in the design of fluorescent probes until recently. In this study, we elaborate systematically on sulfoximine acceptors in fluorescent flipper probes. Fluorescent flippers have been introduced as mechanosensitive probes to image membrane order and tension. They consist of twisted dithienothiophene dimers with sulfide and sulfone bridges to produce the essential primary dipole of the coupled push‐pull system. The objective of this study was to replace the sulfone acceptor by a series of sulfoximines. This is intriguing as a synthetic challenge and worthwhile because the extra nitrogen substituent offers a variability that is attractive to understand and control the performance of the probes. The new sulfoximine flippers provide corroborative evidence for the importance of the primary dipole of the planarizable push‐pull probe. Partitioning into differently ordered membranes and positioning within these different membranes is shown to correlate directly and dramatically with fluorescence lifetimes and mechanosensitivity. Sufficient partitioning into ordered membranes is confirmed as particularly important to image membrane tension by probe compression in the ground state. Compared to the conventional sulfone homolog, the best sulfoximine flipper has more red‐shifted absorption and emission maxima, longer fluorescence lifetime in cell membranes, and larger difference in lifetime upon application of membrane tension.

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“…An interesting extension of the one-pot NH-and O-transfer reaction to sulfides was recently reported by Zheng and Xu, who performed the synthesis of NH-sulfoximines from sulfides in water, harnessing micellar catalysis (Scheme 9). 23 In this case, the generation of the iodonitrene intermediate was achieved from a fluorinated hypervalent iodine (III) reagent and ammonium carbonate as a water-soluble nitrogen source (Scheme 9). Among several surfactants, better yields were observed by using 2 wt% TPGS-750-M, and the sustainability of the process was assessed by recycling of the hypervalent iodine (III) reagent.…”

Section: Oxo-imination Of Sulfides: Synthesis Of Sulfoximinesmentioning

confidence: 99%

Hypervalent iodine (III) reagents and ammonia as useful combination for highly chemoselective N-transfer to low-valent organosulfur compounds and amines

Liuisi¹,

Andresini²,

Colella³

et al. 2021

Arkivoc

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The combination of hypervalent iodine (III) reagents and source of ammonia allows the genesis of iodonitrene species able to act as source of electrophilic nitrogen. Ammonia umpolung represents the net-result of this combination. Since the introduction of this method in 2016, important and unprecedented transformations have been discovered. In this short review we report the state of the art in the use of this type of iodonitrene in modern synthesis.

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Synthesis of NH‐Sulfoximines by Using Recyclable Hypervalent Iodine(III) Reagents under Aqueous Micellar Conditions

Cited by 26 publications

References 92 publications

Cyclic Thiosulfonates for Thiol-Mediated Uptake: Cascade Exchangers, Transporters, Inhibitors

Cyclic Thiosulfonates for Thiol-Mediated Uptake: Cascade Exchangers, Transporters, Inhibitors

Planarizable Push‐Pull Probes with Sulfoximine‐Bridged Dithienothiophene Acceptors

Hypervalent iodine (III) reagents and ammonia as useful combination for highly chemoselective N-transfer to low-valent organosulfur compounds and amines

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