One-pot synthesis of unsymmetrical disulfides using 1-chlorobenzotriazole as oxidant: Interception of the sulfenyl chloride intermediate

Stellenboom, Nashia; Hunter, Roger; Caira, Mino R.

doi:10.1016/j.tet.2010.02.077

Cited by 36 publications

(21 citation statements)

References 46 publications

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“…Yield: 54%, as a yellow oil; 1 H NMR δ (500 MHz, [46] Yield: 67%, as a yellow oil; 1 [47] Yield: 69%, as a yellow oil; 1 [45] Yield: 84%, as a yellow oil; 1 1-(Hexyldisulfanyl)-4-methoxybenzene (17a) [46] Yield: 85%, as a yellow oil; 1 1-(Cyclohexyldisulfanyl)-4-methoxybenzene (18a) [47] Yield: 89%, as a yellow oil; 1…”

Section: -(4-tert-butylbenzyldisulfanyl)-4-methylbenzene (10a)mentioning

confidence: 99%

“…The asymmetric disulfides 7a-11a, 14a-19a, and 21a-22a were synthesized by nucleophilic substitution (Scheme 2, Eq 3) via a sulfenyl chloride intermediate [46] , and all symmetric and asymmetric disulfides were used in the next synthesis step without any further purification. Symmetric and asymmetric disulfides were converted to the corresponding thiosulfinate (Eq 2 and 4) by oxidation, using m-chloroperoxybenzoic acid, to provide our target thiosulfinates.…”

Section: Chemistrymentioning

confidence: 99%

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Synthesis and in vitro biological evaluation of thiosulfinate derivatives for the treatment of human multidrug-resistant breast cancer

2017

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Organosulfur compounds derived from Allium vegetables have long been recognized for various therapeutic effects, including anticancer activity. Allicin, one of the main biologically active components of garlic, shows promise as an anticancer agent; however, instability makes it unsuitable for clinical application. The aim of this study was to investigate the effect of stabilized allicin derivatives on human breast cancer cells in vitro. In this study, a total of 22 stabilized thiosulfinate derivatives were synthesized and screened for their in vitro antiproliferative activities against drug-sensitive (MCF-7) and multidrug-resistant (MCF-7/Dx) human adenocarcinoma breast cancer cells. Assays for cell death, apoptosis, cell cycle progression and mitochondrial bioenergetic function were performed. Seven compounds (4b, 7b, 8b, 13b, 14b, 15b and 18b) showed greater antiproliferative activity against MCF-7/Dx cells than allicin. These compounds were also selective towards multidrug-resistant (MDR) cells, a consequence attributed to collateral sensitivity. Among them, 13b exhibited the greatest anticancer activity in both MCF-7/Dx and MCF-7 cells, with IC values of 18.54±0.24 and 46.50±1.98 μmol/L, respectively. 13b altered cellular morphology and arrested the cell cycle at the G/M phase. Additionally, 13b dose-dependently induced apoptosis, and inhibited cellular mitochondrial respiration in cells at rest and under stress. MDR presents a significant obstacle to the successful treatment of cancer clinically. These results demonstrate that thiosulfinate derivatives have potential as novel anticancer agents and may offer new therapeutic strategies for the treatment of chemoresistant cancers.

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Section: -(4-tert-butylbenzyldisulfanyl)-4-methylbenzene (10a)mentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Synthesis and in vitro biological evaluation of thiosulfinate derivatives for the treatment of human multidrug-resistant breast cancer

2017

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“…In addition, F. Yang et al [ 11 ] have also developed one-pot synthesis of aromatic-aromatic and aromatic-aliphatic disulfide unsymmetrical disulfide using TCCA (Trichloroisocyanuric Acid). N. Stellenboom et al [ [12] , [13] ] prepared unsymmetrical glycosyl disulfides derived from sugar, alkyl/aryl or thiols. M. Bao et al [ 14 ] have developed the N-Trifluoroacetyl arenesulfenamides effective precursors for the synthesis of unsymmetrical disulfides.…”

Section: Introductionmentioning

confidence: 99%

QSAR study of unsymmetrical aromatic disulfides as potent avian SARS-CoV main protease inhibitors using quantum chemical descriptors and statistical methods

Chtita

Belhassan

Bakhouch

et al. 2021

Chemometrics and Intelligent Laboratory Systems

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In silico research was executed on forty unsymmetrical aromatic disulfide derivatives as inhibitors of the SARS Coronavirus (SARS-CoV-1). Density functional theory (DFT) calculation with B3LYP functional employing 6-311+G(d,p) basis set was used to calculate quantum chemical descriptors. Topological, physicochemical and thermodynamic parameters were calculated using ChemOffice software. The dataset was divided randomly into training and test sets consisting of 32 and 8 compounds, respectively. In attempt to explore the structural requirements for bioactives molecules with significant anti-SARS-CoV-2 activity, we have built valid and robust statistics models using QSAR approach. Hundred linear pentavariate and quadrivariate models were established by changing training set compounds and further applied in test set to calculate predicted IC 50 values of compounds. Both built models were individually validated internally as well as externally along with Y-Randomization according to the OECD principles for the validation of QSAR model and the model acceptance criteria of Golbraikh and Tropsha’s. Model 34 is chosen with higher values of R 2 , R 2 test and Q 2 cv (R 2 = 0.838, R 2 test = 0.735, Q 2 cv = 0.757). It is very important to notice that anti-SARS-CoV main protease of these compounds appear to be mainly governed by five descriptors, i.e. highest occupied molecular orbital energy (E HOMO ), energy of molecular orbital below HOMO energy (E HOMO-1 ), Balaban index (BI), bond length between the two sulfur atoms (S1S2) and bond length between sulfur atom and benzene ring (S2Bnz). Here the possible action mechanism of these compounds was analyzed and discussed, in particular, important structural requirements for great SARS-CoV main protease inhibitor will be by substituting disulfides with smaller size electron withdrawing groups. Based on the best proposed QSAR model, some new compounds with higher SARS-CoV inhibitors activities have been designed. Further, in silico prediction studies on ADMET pharmacokinetics properties were conducted.

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“…Cysteine peptides are diagnostically and therapeutically important in many areas of biomedical research (1–6) and thus attractive targets for drug discovery. Consequently, interest in cysteine peptide synthesis has increased significantly (7–9), including the preparation of unsymmetrical disulfides (10,11), formation of oligodeoxynucleotide (ODN)‐peptide covalent linkages (12), and the synthesis of cyclic peptides (13).…”

mentioning

confidence: 99%

Cysteinoyl‐ and Cysteine‐containing Dipeptidoylbenzotriazoles with Free Sulfhydryl Groups: Easy Access to N‐terminal and Internal Cysteine Peptides

et al. 2012

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N‐Protected cysteines 4a–c each with a free sulfhydryl group were prepared in 70–75% yields by treatment of l‐cysteine with 1‐(benzyloxycarbonyl) benzotriazole (Cbz‐Bt) 1a, N‐(tert‐butyloxy‐carbonyl)benzotriazole (Boc‐Bt) 1b, and 1‐(9‐fluorenylmethoxy‐carbonyl)benzotriazole (Fmoc‐Bt) 1c, respectively. N‐Protected, free sulfhydryl cysteines 4a–c were then converted into the corresponding N‐protected, free sulfhydryl cysteinoylbenzotriazoles 7a–c (70–85%), which on treatment with diverse amino acids and dipeptides afforded the corresponding N‐protected, free sulfhydryl N‐terminal cysteine dipeptides 8a–e and tripeptides 8f–h in 73–80% yields. N‐Protected, free sulfhydryl cysteine‐containing dipeptides 9a,b were converted into the corresponding N‐protected, free sulfhydryl dipeptidoylbenzotriazoles 10a,b (69–81%), which on treatment with amino acids, dipeptides, and a tripeptide afforded internal cysteine tripeptides 11a–c, tetrapeptides 11d,e and pentapeptide 11f, each containing a N‐protected, free sulfhydryl groups in 70–90% yields under mild conditions. Treatment of N‐protected, free sulfhydryl cysteinoylbenzotriazole 7a with diamines 12a,b afforded directly the cysteine‐containing disulfide‐bridged cyclic peptides 14a,b in 50% yields.

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One-pot synthesis of unsymmetrical disulfides using 1-chlorobenzotriazole as oxidant: Interception of the sulfenyl chloride intermediate

Cited by 36 publications

References 46 publications

Synthesis and in vitro biological evaluation of thiosulfinate derivatives for the treatment of human multidrug-resistant breast cancer

Synthesis and in vitro biological evaluation of thiosulfinate derivatives for the treatment of human multidrug-resistant breast cancer

QSAR study of unsymmetrical aromatic disulfides as potent avian SARS-CoV main protease inhibitors using quantum chemical descriptors and statistical methods

Cysteinoyl‐ and Cysteine‐containing Dipeptidoylbenzotriazoles with Free Sulfhydryl Groups: Easy Access to N‐terminal and Internal Cysteine Peptides

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