Synthesis and reactions of 2-aryl-8-oxabicycloc[3.2.1]oct-6-en-3-ones

Mann, John; Wilde, Philip D.; Finch, Mark W.

doi:10.1016/s0040-4020(01)87724-3

Cited by 21 publications

(7 citation statements)

References 5 publications

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“…To our surprise, isolation of IE epoxide derivatives was found to be quite elusive. Classic epoxidation conditions − using m -chloroperoxybenzoic acid ( m -CPBA) and t -butyl hydroperoxide ( t BHP), as well as two-step process with N -bromosuccinimide (NBS) and alkali on isoeugenol and acetylated isoeugenol failed to provide the expected epoxides. Only a major adduct of isoeugenol with m -CPBA was produced, whereas reaction with NBS led to the formation of methoxylated phenylpropanoid and benzofuranoid as sole byproducts (SI Figure S14).…”

Section: Resultsmentioning

confidence: 99%

Is Isoeugenol a Prehapten? Characterization of a Thiol-Reactive Oxidative Byproduct of Isoeugenol and Potential Implications for Skin Sensitization

Ahn

Avonto

Chittiboyina

et al. 2020

Chem. Res. Toxicol.

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Isoeugenol is widely used by the cosmetic and fragrance industries, but it also represents a known cause of skin sensitization adverse effects. Although devoid of a structural alert, isoeugenol has been classified as prehapten in virtue of the presence of a pre-Michael acceptor domain. Isoeugenol oxidation could theoretically lead to the generation of reactive toxic quinones, and photoinduced oxidative degradation of isoeugenol was reported to generate strongly thiol reactive byproducts. Nonetheless, the isoeugenol degradation product responsible for increased reactivity was found to be elusive. In the present study, an aged isoeugenol sample was subjected to reactivity-guided experiments to trap elusive thiol reactive species with a fluorescent nucleophile, viz. dansyl cysteamine (DCYA). The results herein presented demonstrate that photo-oxidation of isoeugenol led to the formation of a dimeric 7,4′-oxyneolignan with strong chemical reactivity, capable of nucleophilic substitution with thiols. The results were confirmed by isolation, structural characterization, and further NMR reactivity studies. Isoeugenol is already well-known as moderately reactive in thiol depletion assays, and was herein demonstrated to be capable of converting to more potent electrophilic species upon degradation, thus acting as a prehapten. The application of the reactivity-guided strategy described herein was shown to serve as an effective tool to investigate elusive skin sensitizers.

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Section: Resultsmentioning

confidence: 99%

Is Isoeugenol a Prehapten? Characterization of a Thiol-Reactive Oxidative Byproduct of Isoeugenol and Potential Implications for Skin Sensitization

Ahn

Avonto

Chittiboyina

et al. 2020

Chem. Res. Toxicol.

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“…In a medium of intermediate polarity and proton donor ability, mixtures of 25 and 26 were formed. These results can be explained by the assumption that in an aprotic and mildly polar medium a concerted cyclopropanone formation is favored, whereas in a protic and polar medium a nonconcerted pathway involving a dipolar intermediate is 3-Aryl propanoic acid esters, produced via a Favorskii rearrangement, were obtained as major side-products when the cycloaddition reaction between furan and the oxyallyl cations generated from 1-aryl-1-bromopropanones were tried [24]. The rearrangement was only observed when the aryl ring was moderately electron-rich.…”

Section: -Bromo Ketonesmentioning

confidence: 99%

The Favorskii Rearrangement: Synthetic Applications

Guijarro¹,

Yus²

2005

COC

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“…This may allow for protonation of the enol ether, which may initiate a cation-mediated cycloreversion reaction (as is illustrated in Scheme A). Mann and co-workers disclosed a mechanistically related fragmentation that supports this proposal (Scheme B) . This could happen either through sp hybridized oxonium formation (as shown) or through a hemiacetal or hydrate intermediate.…”

Section: Resultsmentioning

confidence: 52%

“…Mann and co-workers disclosed a mechanistically related fragmentation that supports this proposal (Scheme 8B). 25 This could happen either through sp hybridized oxonium formation (as shown) or through a hemiacetal or hydrate intermediate. However, no noticeable differences in reactivity were observed when the reaction was run over molecular sieves.…”

Section: ■ Results and Discussionmentioning

confidence: 91%

Triflic Acid-Mediated Rearrangements of 3-Methoxy-8-oxabicyclo[3.2.1]octa-3,6-dien-2-ones: Synthesis of Methoxytropolones and Furans

et al. 2013

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Methoxytropolones are useful scaffolds for therapeutic development due to their known biological activity and established value in the synthesis of α-hydroxytropolones. Upon treatment with triflic acid, a series of 3-methoxy-8-oxabicyclo[3.2.1]octa-3,6-dien-2-ones rearrange rapidly and cleanly to form methoxytropolones. Interestingly, bicycles that are derived from dimethyl acetylenedicarboxylate (R2=R3=CO2Me) instead form furans as the major product.

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Synthesis and reactions of 2-aryl-8-oxabicycloc[3.2.1]oct-6-en-3-ones

Cited by 21 publications

References 5 publications

Is Isoeugenol a Prehapten? Characterization of a Thiol-Reactive Oxidative Byproduct of Isoeugenol and Potential Implications for Skin Sensitization

Is Isoeugenol a Prehapten? Characterization of a Thiol-Reactive Oxidative Byproduct of Isoeugenol and Potential Implications for Skin Sensitization

The Favorskii Rearrangement: Synthetic Applications

Triflic Acid-Mediated Rearrangements of 3-Methoxy-8-oxabicyclo[3.2.1]octa-3,6-dien-2-ones: Synthesis of Methoxytropolones and Furans

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