Ring opening reactions of heterocycles with selenium and tellurium nucleophiles

The control of cysteine reactivity is of paramount importance for the synthesis of proteins using the native chemical ligation (NCL) reaction. We report that this goal can be achieved in a traceless manner during ligation by appending a simple N-selenoethyl group to cysteine. While in synthetic organic chemistry the cleavage of carbon-nitrogen bonds is notoriously difficult, we describe that N-selenoethyl cysteine (SetCys) loses its selenoethyl arm in water under mild conditions upon reduction of its selenosulfide bond. Detailed mechanistic investigations show that the cleavage of the selenoethyl arm proceeds through an anionic mechanism with assistance of the cysteine thiol group. The implementation of the SetCys unit in a process enabling the modular and straightforward assembly of linear or backbone cyclized polypeptides is illustrated by the synthesis of biologically active cyclic hepatocyte growth factor variants.

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Section: Resultsmentioning

confidence: 99%

A cysteine selenosulfide redox switch for protein chemical synthesis

et al. 2020

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“…Finally, we further enlarge the scope of this procedure with variously substituted diselenides allowing the synthesis of organoselenides 8a-c from diselenides 6a-c and diselenides 6a,b,d,e gave N-(4-(benzylselanyl)phenyl)acetamides 9a-d, bearing two selenated moieties onto the same molecular skeleton ( Figure 2). Additionally, on the basis of our recent findings on the reactivity of selenols with elecrophiles [17][18][19][20], we also evaluated an alternative and milder approach to 2-seleno-acetamides 7-9. Thus, aryl-and alkyl-selenols 10a-d were efficiently deprotonated by using a Cs 2 CO 3 /TBAI system [21,22] and then treated with 2-chloroacetamides 2a-c to afford the corresponding selenium-containing acetamides 7-9 in good yield (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

Evaluation of Thio- and Seleno-Acetamides Bearing Benzenesulfonamide as Inhibitor of Carbonic Anhydrases from Different Pathogenic Bacteria

Angeli

Pinteala²,

Maier³

et al. 2020

IJMS

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A series of 2-thio- and 2-seleno-acetamides bearing the benzenesulfonamide moiety were evaluated as Carbonic Anhydrase (CA, EC 4.2.1.1) inhibitors against different pathogenic bacteria such as the Vibrio cholerae (VchCA-α and VchCA-β), Burkholderia pseudomallei (BpsCA-β and BpsCA-γ), Mycobacterium tuberculosis (Rv3723-β) and the Salmonella enterica serovar Typhimurium (StCA2-β). The molecules represent interesting leads worth developing as innovative antibacterial agents since they possess new mechanism of action and isoform selectivity preferentially against the bacterial expressed CAs. The identification of potent and selective inhibitors of bacterial CAs may lead to tools also useful for deciphering the physiological role(s) of such proteins.

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“…The proposed mechanism is reminiscent of the cleavage of alkylamines by phenylselenol, albeit such reactions usually require elevated temperatures and/or assistance by metals. 16,17,32 Intrigued by the ease of SetCys to Cys conversion, we sought to determine if the SetCys thiol participates to the departure of the 2-selanylethyl limb. To this end, a N-(2-selanylethyl)-alanyl (SetAla) peptide analogue was prepared and treated with MPAA/TCEP/ascorbate at the optimal pH for the SetCys to Cys conversion, i.e., pH 6.0 ( Figure 3d).…”

Section: Insights Into the Conversion Of Setcys To A Cys Residuementioning

confidence: 99%

A Cysteine Selenosulfide Redox Switch for Protein Chemical Synthesis

Diemer¹,

Ollivier²,

Leclercq³

et al. 2020

Preprint

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The control of cysteine reactivity is of paramount importance for the synthesis of proteins using the native chemical ligation (NCL) reaction. We discovered that this goal can be achieved in a traceless manner during ligation by appending a simple N-selenoethyl group to cysteine. While in synthetic organic chemistry the cleavage of carbon-nitrogen bonds is notoriously difficult, we found that N-selenoethyl cysteine (SetCys) loses its selenoethyl arm in water under mild conditions upon reduction of its selenosulfide bond. Detailed mechanistic investigations uncover a novel mode of reactivity for Cys. Its implementation in a process enabling the modular and straightforward assembly of linear or backbone cyclized polypeptides is illustrated by the synthesis of biologically active cyclic hepatocyte growth factor variants.<br>

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Ring opening reactions of heterocycles with selenium and tellurium nucleophiles

Abstract: An overview of the preparation and synthetic potentialities of functionalized organoselenium and organotellurium compounds is presented.

Cited by 43 publications

References 104 publications

A cysteine selenosulfide redox switch for protein chemical synthesis

A cysteine selenosulfide redox switch for protein chemical synthesis

Evaluation of Thio- and Seleno-Acetamides Bearing Benzenesulfonamide as Inhibitor of Carbonic Anhydrases from Different Pathogenic Bacteria

A Cysteine Selenosulfide Redox Switch for Protein Chemical Synthesis

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