Catalytic Enantioselective 1,3‐Alkyl Shift in Alkyl Aryl Ethers: Efficient Synthesis of Optically Active 3,3′‐Diaryloxindoles

Gade, Amol B.; Bagle, Pradip N.; Shinde, Popat S.; Bhardwaj, Vipin; Banerjee, Subhrashis; Chande, Ajit; Patil, Nitin T.

doi:10.1002/ange.201801650

Cited by 10 publications

(3 citation statements)

References 87 publications

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“…The route in Scheme 3A yields usable quantities of material; however, inconsistent yields, impurity formation, and multiple batch failures were observed upon scale-up. Taking inspiration from other work on the synthesis of 3,3,-disubstituted oxindoles utilizing heteroatom nucleophiles, 30,31 we found that employing THF as the solvent (step 1, Scheme 3B) yielded a cleaner tertiary chloride intermediate. Changing to a more basic reaction with excess cesium carbonate in dichloromethane with overnight stirring followed by TBAF deprotection was a highly efficient route to compound 2, produced in 95% yield over three steps (Scheme 3B).…”

Section: ■ Resultsmentioning

confidence: 90%

Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer

et al. 2022

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Approximately 75% of breast cancers are estrogen receptor alpha-positive (ERα+), and targeting ERα directly with ERα antagonists/degraders or indirectly with aromatase inhibitors is a successful therapeutic strategy. However, such treatments are rarely curative and development of resistance is universal. We recently reported ErSO, a compound that induces ERα-dependent cancer cell death through a mechanism distinct from clinically approved ERα drugs, via hyperactivation of the anticipatory unfolded protein response. ErSO has remarkable tumor-eradicative activity in multiple ERα+ tumor models. While ErSO has promise as a new drug, it has effects on ERα-negative (ERα−) cells in certain contexts. Herein, we construct modified versions of ErSO and identify variants with enhanced differential activity between ERα+ and ERα– cells. We report ErSO-DFP, a compound that maintains antitumor efficacy, has enhanced selectivity for ERα+ cancer cells, and is well tolerated in rodents. ErSO-DFP and related compounds represent an intriguing new class for the treatment of ERα+ cancers.

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Section: ■ Resultsmentioning

confidence: 90%

Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer

et al. 2022

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“…Patil and co-workers expanded an efficient and mild chiral Brønsted acid catalyzed asymmetric 1,3-alkyl shift of alkyl aryl ethers 23. 58 A broad range of substituted enantiomers of 3,3′-diaryloxindoles 24 have been prepared with good to excellent yields (up to 88% yield, 99% ee). As a demonstration of the scalability of this system, this reaction can be readily scaled up to 3 mmol without significant loss of efficiency.…”

Section: Brønsted Acid Catalysismentioning

confidence: 99%

Recent advances in catalytic asymmetric [1,3]-rearrangement reactions

Zhang

Chen

2022

Org. Chem. Front.

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“…Cell growth assays were carried out using MTT (3-(4,5dimethylthiazol-2-yl)-2,5-diph-enyltetrazolium bromide) reagent (Sigma, USA) as described previously [52]. In brief, transfected cells were trypsinized, counted, and plated into 96-well plates.…”

Section: Mtt Assaysmentioning

confidence: 99%

CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells

Chen

Jiang

et al. 2020

Cell Commun Signal

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Introduction Radioresistance is a major challenge in lung cancer radiotherapy, and new radiosensitizers are urgently needed. Estrogen receptor β (ERβ) is involved in the progression of non-small cell lung cancer (NSCLC), however, the role of ERβ in the response to radiotherapy in lung cancer remains elusive. In the present study, we investigated the mechanism underlying ERβ-mediated transcriptional activation and radioresistance of NSCLC cells. Methods Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the expression of CLPTM1L, ERβ and other target genes. The mechanism of CLPTM1L in modulation of radiosensitivity was investigated by chromatin immunoprecipitation assay, luciferase reporter gene assay, immunofluorescence staining, confocal microscopy, coimmunoprecipitation and GST pull-down assays. The functional role of CLPTM1L was detected by function assays in vitro and in vivo. Results CLPTM1L expression was negatively correlated with the radiosensitivity of NSCLC cell lines, and irradiation upregulated CLPTM1L in radioresistant (A549) but not in radiosensitive (H460) NSCLC cells. Meanwhile, IR induced the translocation of CLPTM1L from the cytoplasm into the nucleus in NSCLC cells. Moreover, CLPTM1L induced radioresistance in NSCLC cells. iTRAQ-based analysis and cDNA microarray identified irradiation-related genes commonly targeted by CLPTM1L and ERβ, and CLPTM1L upregulated ERβ-induced genes CDC25A, c-Jun, and BCL2. Mechanistically, CLPTM1L coactivated ERβ by directly interacting with ERβ through the LXXLL NR (nuclear receptor)-binding motif. Functionally, ERβ silencing was sufficient to block CLPTM1L-enhanced radioresistance of NSCLC cells in vitro. CLPTM1L shRNA treatment in combination with irradiation significantly inhibited cancer cell growth in NSCLC xenograft tumors in vivo. Conclusions The present results indicate that CLPTM1L acts as a critical coactivator of ERβ to promote the transcription of its target genes and induce radioresistance of NSCLC cells, suggesting a new target for radiosensitization in NSCLC therapy.

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Catalytic Enantioselective 1,3‐Alkyl Shift in Alkyl Aryl Ethers: Efficient Synthesis of Optically Active 3,3′‐Diaryloxindoles

Cited by 10 publications

References 87 publications

Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer

Activators of the Anticipatory Unfolded Protein Response with Enhanced Selectivity for Estrogen Receptor Positive Breast Cancer

Recent advances in catalytic asymmetric [1,3]-rearrangement reactions

CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells

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