A novel synthesis and transformations of isothiochroman 2,2-dioxide

Shyshkina, Olena O.; Tkachuk, T. M.; Volovnenko, T. A.; Volovenko, Yulian M.; Zubatyuk, Roman I.; Medviediev, Volodymyr V.; Шишкин, Олег В.

doi:10.1016/j.tetlet.2012.05.163

Cited by 10 publications

(3 citation statements)

References 16 publications

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“…Following up on this result, the phenyl-conjugated derivative of 31a , isothiochroman-4-one 2,2-dioxide ( 31b ) was prepared using a three-step literature reported procedure. 55 Like 31a , the keto form of 31b predominates (Table S1, † Entry F) and showed a rate enhancement of almost 70-fold ( k obs = 54.9 min –1 ), when compared to dimedone ( 1 ). Another direct follow-up to 31a is the class of compounds in which the sulfone is replaced with a sulfonamide moiety, as in 2-alkyl-1,2-thiazinan-5-one 1,1-dioxide ( 31c , d ) 56 and 2-alkyl-2 H -1,2-thiazin-5(6 H )-one 1,1-dioxide ( 31e , f ) 57 (prepared as described in Scheme S17 † ).…”

Section: Resultsmentioning

confidence: 99%

Profiling the reactivity of cyclic C-nucleophiles towards electrophilic sulfur in cysteine sulfenic acid

2016

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Oxidation of a protein cysteine thiol to sulfenic acid, termed S-sulfenylation, is a reversible post-translational modification that plays a crucial role in regulating protein function and is correlated with disease states. The majority of reaction-based small molecule and immunochemical probes used for detecting sulfenic acids are based on the 5,5-dimethyl-1,3-cyclohexanedione (dimedone) scaffold, which is selective, but suffers from low reactivity. In addition, mechanistic details and features that diminish or enhance nucleophile reactivity remain largely unknown. A significant hurdle to resolving the aforementioned issues has been the chemically unstable nature of small-molecule sulfenic acid models. Herein, we report a facile mass spectrometry-based assay and repurposed dipeptide-based model to screen a library of cyclic C-nucleophiles for reactivity with sulfenic acid under aqueous conditions. Observed rate constants for ~100 cyclic C-nucleophiles were obtained and, from this collection, we have identified novel compounds with more than 200-fold enhanced reactivity, as compared to dimedone. The increase in reactivity and retention of selectivity of these C-nucleophiles were validated in secondary assays, including a protein model for sulfenic acid. Together, this work represents a significant step toward developing new chemical reporters for detecting protein S-sulfenylation with superior kinetic resolution. The enhanced rates and varied composition of the C-nucleophiles should enable more comprehensive analyses of the sulfenome and serve as the foundation for reversible or irreversible nucleophilic covalent inhibitors that target oxidized cysteine residues in therapeutically important proteins.

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Section: Resultsmentioning

confidence: 99%

Profiling the reactivity of cyclic C-nucleophiles towards electrophilic sulfur in cysteine sulfenic acid

2016

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“…The synthesis of 1H-isothiochromen-4(3H)-one 2,2-dioxide (1) has been described [13,15,16] previously. Enamine 2 was synthesized by treating 1 with dimethylformamide dimethylacetal (DMF-DMA) (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

Novel transformations of 1H-isothiochromen-4(3H)-one 2,2-dioxide

et al. 2012

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“…However, the reaction of 3j with PhMgBr delivered the 1,4-addition product 11 in 74% yield (Scheme 3, d). Decarboxylation of 3b by refluxing in aqueous NaOH solution 24 or by reflux in aque-ous AcOH/HCl solution failed. 25 Finally, using Happer's decarboxylation procedure, 26 3b was directly converted into hCA II inhibitor 12 in 66% yield in only one step (Scheme 3, e).…”

Section: Paper Syn Thesismentioning

confidence: 99%

A Tandem Sulfonylation and Knoevenagel Condensation for the Preparation of Sulfocoumarin-3-carboxylates

Dong

Yang

et al. 2019

Synthesis

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Sulfocoumarins are key structural motifs in several bioactive molecules. Herein, we describe a simple, one-pot procedure for the synthesis of structurally diverse sulfonocoumarin-3-carboxylates by heating 2-hydroxyaryl aldehydes with an active sulfonyl chloride in the presence of pyridine. The process tolerates numerous functional groups including alkoxy, alkyl, halogen, nitro, and even nucleophilic phenolic hydroxy. Additionally, reactions of 2-hydroxyaryl ketones and 2-methylaminoaryl aldehydes give 4-substituted sulfocoumarins and 1-aza-2-sulfocoumarins, respectively. A gram-scale synthesis and further derivatizations are also reported. The ester group is easily removed via Happer’s decarboxylation.

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A novel synthesis and transformations of isothiochroman 2,2-dioxide

Cited by 10 publications

References 16 publications

Profiling the reactivity of cyclic C-nucleophiles towards electrophilic sulfur in cysteine sulfenic acid

Profiling the reactivity of cyclic C-nucleophiles towards electrophilic sulfur in cysteine sulfenic acid

Novel transformations of 1H-isothiochromen-4(3H)-one 2,2-dioxide

A Tandem Sulfonylation and Knoevenagel Condensation for the Preparation of Sulfocoumarin-3-carboxylates

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