Microwave-Based Reaction Screening: Tandem Retro-Diels–Alder/Diels–Alder Cycloadditions of<i>o</i>-Quinol Dimers

Dong, Suwei; Cahill, Kath arine J.; Kang, Moon Il; Colburn, Nancy H.; Henrich, Curtis J.; Wilson, Jennifer A.; Beutler, John A.; Johnson, Richard P.; Porco, John A.

doi:10.1021/jo201658y

Cited by 31 publications

(27 citation statements)

References 54 publications

(86 reference statements)

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“…However, only a small amount of product 19h was isolated (entry 8), presumably due to the multiple reaction sites for the generated cyclopentadienone intermediate. In all cases, reactions to form [4+2] adducts proceeded in high diastereoselectivity which was in accordance with previous observations in our synthesis of chamaecypanone C. 5a Endo -selectivity and facial-selectivity align well with the observed reactivity of o -quinols, 35 wherein the bulky aromatic substituents are oriented away from the sterically demanding quaternary center.…”

Section: Resultssupporting

confidence: 90%

Synthesis of Chamaecypanone C Analogues from in Situ-Generated Cyclopentadienones and Their Biological Evaluation

Dong

Qin

Hamel³

et al. 2012

J. Am. Chem. Soc.

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A rhodium-catalyzed dehydrogenation protocol has been developed for conversion of 3,5-diarylcyclopentenones to the corresponding 2,4-diarylcyclopentadienones. Using this protocol, analogues of the cytotoxic agent chamaecypanone C have been synthesized via Diels-Alder cycloaddition between the cyclopentadienones and in situ-generated ortho-quinols. Biological evaluation of these analogues revealed a compound with higher activity as a microtubule inhibitor and cytotoxic agent in comparison with the parent structure.

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Section: Resultssupporting

confidence: 90%

Synthesis of Chamaecypanone C Analogues from in Situ-Generated Cyclopentadienones and Their Biological Evaluation

Dong

Qin

Hamel³

et al. 2012

J. Am. Chem. Soc.

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“…150 Moreover, (−)- 97 does not display inhibition of HIF-2, NF-κB, or SRE dependent transcription at the same concentration. However, during the experiments in the NCI 60-cell screen at 10 μM, (−)- 97 did not pass the threshold for further evaluation of cell growth inhibition.…”

Section: Development Of Small Molecules Targeting Ap-1mentioning

confidence: 97%

Small Molecule Inhibitors Targeting Activator Protein 1 (AP-1)

et al. 2014

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Activator protein 1 (AP-1) is a pivotal transcription factor that regulates a wide range of cellular processes including proliferation, apoptosis, differentiation, survival, cell migration, and transformation. Accumulating evidence supports that AP-1 plays an important role in several severe disorders including cancer, fibrosis, and organ injury, as well as inflammatory disorders such as asthma, psoriasis, and rheumatoid arthritis. AP-1 has emerged as an actively pursued drug discovery target over the past decade. Excitingly, a selective AP-1 inhibitor T-5224 (51) has been investigated in phase II human clinical trials. Nevertheless, no effective AP-1 inhibitors have yet been approved for clinical use. Despite significant advances achieved in understanding AP-1 biology and function, as well as the identification of small molecules modulating AP-1 associated signaling pathways, medicinal chemistry efforts remain an urgent need to yield selective and efficacious AP-1 inhibitors as a viable therapeutic strategy for human diseases.

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“…Dong et al recently reported an interesting MW-assisted parallel reaction screening for evaluation of the Diels-Alder cycloaddition of o-quinol dimers in order to identify reactive reaction partners and bioactive compounds [98]. The reaction between o-quinol dimers (252) and various dienes or dienophiles under MW activation led to bicyclo[2.2.2]octenones (253/254) via retro-[4 + 2]-followed by [4 + 2]-cycloaddition with external dienophiles (Scheme 17.43).…”

Section: Intermolecular Diels-alder Reactionsmentioning

confidence: 99%

“…The nonthermal MW effects, demonstrated by the absence of reaction products when the reactions were carried out under conventional heating conditions, were explained by considering the development of polarities between ground state and transition state generated from PM3 calculations of the dipole moments of reagents, products, and transition states[41].Willy et al developed the synthesis of 3,4,5-substituted isoxazoles (102) by a one-pot, three-component reaction pathway[42]. Alkynyl ketones (100) (Scheme 17.13), obtained by coupling of acid chlorides(98) with terminal alkynes…”

mentioning

confidence: 99%