Author
Wenbo Sun
Bio: Wenbo Sun is an academic researcher. The author has contributed to research in topics: Catalysis & Aryl. The author has an hindex of 1, co-authored 1 publications receiving 2 citations.
Topics: Catalysis, Aryl, Photoredox catalysis
Papers
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TL;DR: In this paper, a highly efficient approach to C(sp3)-C(sp 3) bond construction via photoredox catalysis between on-DNA alkenes and N-aryl tertiary amines was developed.
16 citations
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TL;DR: A visible light-promoted divergent synthesis of on-DNA benzoheterocycles from aldehydes is presented, demonstrating the feasibility of this approach in DNA-encoded chemical library construction.
14 citations
TL;DR: In this article, the authors abstracted and analyzed DNA-encoded libraries from the literature to assess the synthesis strategy, selections of reactions and monomers and their propensity to reveal hits.
12 citations
TL;DR: A Giese addition is reported to install highly functionalized bicyclo-BCPs using tricyclo-TCP as a radical linchpin, as well as other diverse alkyl groups, on-DNA from the corresponding organohalides as non-stabilized radical precursors.
Abstract: DNA-encoded libraries have proven their tremendous value in the identification of new lead compounds for drug discovery. To access libraries in new chemical space, many methods have emerged to transpose traditional mol-scale reactivity to nmol-scale, on-DNA chemistry. However, procedures to access libraries with a greater fraction of C(sp3) content are still limited, and the need to "escape from flatland" more readily on-DNA remains. Herein, we report a Giese addition to install highly functionalized bicyclo[1.1.1]pentanes (BCPs) using tricyclo[1.1.1.01,3]pentane (TCP) as a radical linchpin, as well as other diverse alkyl groups, on-DNA from the corresponding organohalides as non-stabilized radical precursors. Telescoped procedures allow extension of the substrate pool by at least an order of magnitude to ubiquitous alcohols and carboxylic acids, allowing us to "upcycle" these abundant feedstocks to afford non-traditional libraries with different physicochemical properties for the small-molecule products (i.e., non-peptide libraries with acids). This approach is amenable to library production, as a DNA damage assessment revealed good PCR amplifiability and only 6% mutated sequences for a full-length DNA tag.
12 citations
TL;DR: The deaminative alkylation method is believed to offer a high potential for constructing DNA-encoded libraries, as was demonstrated by the production of a mock library in a 2 × 3 matrix format and confirmation of DNA stability by UPLC-MS and qPCR experiments.
10 citations
TL;DR: Forging carbon-carbon linkage in DNA-encoded combinatorial library synthesis represents a fundamental task for drug discovery, especially with broad substrate scope and exquisite functional group tolerance.
Abstract: Forging carbon–carbon (C–C) linkage in DNA-encoded combinatorial library synthesis represents a fundamental task for drug discovery, especially with broad substrate scope and exquisite functional group tolerance. Here we reported the palladium-catalyzed Suzuki–Miyaura, Heck and Hiyama type cross-coupling via DNA-conjugated aryl diazonium intermediates for DNA-encoded chemical library (DEL) synthesis. Starting from commodity arylamines, this synthetic route facilely delivers vast chemical diversity at a mild temperature and pH, thus circumventing damage to fragile functional groups. Given its orthogonality with traditional aryl halide-based cross-coupling, the aryl diazonium-centered strategy expands the compatible synthesis of complex C–C bond-connected scaffolds. In addition, DNA-tethered pharmaceutical compounds (e.g., HDAC inhibitor) are constructed without decomposition of susceptible bioactive warheads (e.g., hydroxamic acid), emphasizing the superiority of the aryl diazonium-based approach. Together with the convenient transformation into an aryl azide photo-crosslinker, aryl diazonium's DNA-compatible diversification synergistically demonstrated its competence to create medicinally relevant combinatorial libraries and investigate protein–ligand interactions in pharmaceutical research.
5 citations