Dataset Information

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes.

ABSTRACT: An efficient copper-promoted hydration reaction and its application in the synthesis of benzo[b]furan and benzo[b]thiophene derivatives is presented starting from readily available 2-fluorophenylacetylene derivatives. The key annulation step involves the hydration of the C-F bond of 2-fluorophenylacetylene derivatives followed by an intramolecular annulation to afford benzo[b]furan and benzo[b]thiophene derivatives. Moreover, structurally important 2,2'-bisbenzofuran scaffolds are provided in good yields.

SUBMITTER: Li Y

PROVIDER: S-EPMC4273265 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes.

Li Yibiao Y Cheng Liang L Liu Xiaohang X Li Bin B Sun Ning N

Beilstein journal of organic chemistry 20141204

An efficient copper-promoted hydration reaction and its application in the synthesis of benzo[b]furan and benzo[b]thiophene derivatives is presented starting from readily available 2-fluorophenylacetylene derivatives. The key annulation step involves the hydration of the C-F bond of 2-fluorophenylacetylene derivatives followed by an intramolecular annulation to afford benzo[b]furan and benzo[b]thiophene derivatives. Moreover, structurally important 2,2'-bisbenzofuran scaffolds are provided in go ...[more]

PMID: 25550754

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Project description:Structural alerts are commonly used in drug discovery to identify molecules likely to form reactive metabolites and thereby become toxic. Unfortunately, as useful as structural alerts are, they do not effectively model if, when, and why metabolism renders safe molecules toxic. Toxicity due to a specific structural alert is highly conditional, depending on the metabolism of the alert, the reactivity of its metabolites, dosage, and competing detoxification pathways. A systems approach, which explicitly models these pathways, could more effectively assess the toxicity risk of drug candidates. In this study, we demonstrated that mathematical models of P450 metabolism can predict the context-specific probability that a structural alert will be bioactivated in a given molecule. This study focuses on the furan, phenol, nitroaromatic, and thiophene alerts. Each of these structural alerts can produce reactive metabolites through certain metabolic pathways but not always. We tested whether our metabolism modeling approach, XenoSite, can predict when a given molecule's alerts will be bioactivated. Specifically, we used models of epoxidation, quinone formation, reduction, and sulfur-oxidation to predict the bioactivation of furan-, phenol-, nitroaromatic-, and thiophene-containing drugs. Our models separated bioactivated and not-bioactivated furan-, phenol-, nitroaromatic-, and thiophene-containing drugs with AUC performances of 100%, 73%, 93%, and 88%, respectively. Metabolism models accurately predict whether alerts are bioactivated and thus serve as a practical approach to improve the interpretability and usefulness of structural alerts. We expect that this same computational approach can be extended to most other structural alerts and later integrated into toxicity risk models. This advance is one necessary step toward our long-term goal of building comprehensive metabolic models of bioactivation and detoxification to guide assessment and design of new therapeutic molecules.

Dataset Information

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes.

Publications

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes.

Similar Datasets

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