Modular, stereocontrolled C β –H/C α –C activation of alkyl carboxylic acids
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Abstract
Significance: The combination of two newly emerging methods for chemical synthesis enables access to molecular space that was previously challenging or impossible to access. Thus, a C–H activation of ubiquitous carboxylic acids followed by their decarboxylative functionalization provides modular access to difunctionalized carbon frameworks with distinctly controlled stereochemistry. Application of this strategy to simplify the synthesis of medicinally important entities and to discover potent antimalarial compounds is described.
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Several of the enantiopure fragment recognition groups deployed herein are poised for direct modification using synthetic methodologies such as C-H bond activation chemistry.
“Toward this end, we note that the enantioprobes offer a convenient target engagement assay for assessing competitive binding of elaborated analogues in cells, and that several of the enantiopure fragment recognition groups deployed herein are poised for direct modification using synthetic methodologies such as C-H bond activation chemistry44–46.”
From Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs (2019) · cites this paper as [44]
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- Authors
- Shang, M., Feu, K. S., Vantourout, J. C., Barton, L. M., Osswald, H. L., Kato, N., Gagaring, K., McNamara, C. W., Chen, G., Hu, L., Ni, S., Fernández-Canelas, P., Chen, M., Merchant, R. R., Qin, T., Schreiber, S. L., Melillo, B., Yu, J.-Q., & Baran, P. S.
- Affiliations
- Scripps Research Institute (US)
- Broad Institute (US)
- Corresponding author
- Melillo, Bruno
- Yu, Jin-Quan
- Baran, Phil S.
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-04-17
- Volume
- 116
- Issue
- 18
- Pages
- 8721-8727
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6500144
- OpenAlex
- W2937850742
- Cited by
- 53
- References
- 72
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 5 · 2023: 5 · 2022: 9 · 2021: 6 · 2020: 13 · 2019: 6
- FWCI
- 3.33
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion, cc-by)
- ChemRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Royal College of Surgeons in Ireland (submittedVersion, cc-by-nc-nd)
- Funders
- HHS | National Institutes of Health (GM-118176)
- Bill and Melinda Gates Foundation (OPP11823830)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Catalytic C–H Functionalization Methods
- Physical Sciences › Chemistry › Organic Chemistry › Cyclopropane Reaction Mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Asymmetric Synthesis and Catalysis
- Keywords
- C–H activation, decarboxylative coupling, alkyl carboxylic acids, asymmetric synthesis, stereocontrol, vicinal difunctionalization, modular synthesis, diversity-oriented synthesis, antimalarial compounds
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