Bioconjugation by Native Chemical Tagging of C–H Bonds

Zhou, Qianghui; Gui, Jinghan; Pan, Chung‐Mao; Albone, Earl F.; Cheng, Xin; Suh, Edward M.; Grasso, Luigi; Ishihara, Yoshihiro; Baran, Phil S.

doi:10.1021/ja407739y

Cited by 115 publications

(94 citation statements)

References 25 publications

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“…101 A new sulfinate reagent, diflouroalkylazidosulfinate-sodium (DASS-Na), was developed for the late-stage functionalization of heteroaromatics that to append an alkyl azide moiety onto a small molecule of interest. 99 Chemical biology technologies, such as target engagement studies, use click chemistry as a means for bioorthogonal functionalization 100 and heavily rely on easy functionalization of drug like small molecules.…”

Section: A Series Of Collaborations Betweenmentioning

confidence: 99%

Modern advances in heterocyclic chemistry in drug discovery

et al. 2016

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New advances in synthetic methodologies that allow rapid access to a wide variety of functionalized heterocyclic compounds are of critical importance to the medicinal chemist as it provides the ability to expand the available drug-like chemical space and drive more efficient delivery of drug discovery programs. Furthermore, the development of robust synthetic routes that can readily generate bulk quantities of a desired compound help to accelerate the drug development process. While established synthetic methodologies are commonly utilized during the course of a drug discovery program, the development of innovative heterocyclic syntheses that allow for different bond forming strategies are having a significant impact in the pharmaceutical industry. This review will focus on recent applications of new methodologies in C-H activation, photoredox chemistry, borrowing hydrogen catalysis, multicomponent reactions, regio- and stereoselective syntheses, as well as other new, innovative general syntheses for the formation and functionalization of heterocycles that have helped drive project delivery. Additionally, the importance and value of collaborations between industry and academia in shaping the development of innovative synthetic approaches to functionalized heterocycles that are of greatest interest to the pharmaceutical industry will be highlighted.

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Section: A Series Of Collaborations Betweenmentioning

confidence: 99%

Modern advances in heterocyclic chemistry in drug discovery

et al. 2016

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“…3 In a recent report, a sulfinate salt was used to append a trifluoromethyl group onto (−)-agelastatin A, which led to the synthesis of the most potent derivative of this natural product. 4 The surging commercial demand for sulfinate reagents pointed to a clear drawback in that only a limited set are currently available.…”

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confidence: 99%

Simple Sulfinate Synthesis Enables CH Trifluoromethylcyclopropanation

et al. 2014

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A simple method to convert readily available carboxylic acids into sulfinate salts employing an interrupted Barton decarboxylation reaction is reported. A medicinally oriented panel of ten new sulfinate reagents was created using this method, including a key trifluoromethylcyclopropanation reagent TFCS-Na. The reactivity of six of these salts towards C–H functionalization was field-tested using several different classes of heterocycles.

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“…73 This strategy is based on (flouro)alkanesulfinate reagents and their ability to form radicals in situ under oxidative conditions, that then react with heteroaromatics through a formal C–H functionalization. 79–81 The azide-containing alkylsulfinate 68 allows the direct derivatization of various heterocycles and the resulting azidoalkyl chain can then be used for conjugation to reporter tags, as demostrated by the attachment of the derivatized products to an alkyne-containing monoclonal antibody through a Hüisgen cycloaddition.…”

Section: Addendummentioning

confidence: 99%

Chemo- and site-selective derivatizations of natural products enabling biological studies

2014

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Bioactive natural products and derivatives remain an enduring starting point for the discovery of new cellular targets for disease intervention and lead compounds for the development of new therapeutic agents. The former goal is accomplished through the synthesis of bioactive cellular probes from natural products enabling insights into the mechanism of action of these natural products by classical affinity chromatography or more recent proteome profiling methods. However, the direct and selective modification of native natural products for these purposes remains a challenge due to the structural complexity and the wide functional group diversity found in these natural substances. The lack of selective synthetic methods available to directly manipulate unprotected complex small molecules, in particular to perform structure-activity relationship studies and prepare appropriate cellular probes, has recently begun to be addressed benefitting from the broader emerging area of chemoselective synthetic methodology. Thus, new reagents, catalysts and reaction processes are enabling both chemo- and site-selective modifications of complex, native natural products. In this review, we describe selected recent examples of these functionalization strategies in this emerging area.

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Bioconjugation by Native Chemical Tagging of C–H Bonds

Cited by 115 publications

References 25 publications

Modern advances in heterocyclic chemistry in drug discovery

Modern advances in heterocyclic chemistry in drug discovery

Simple Sulfinate Synthesis Enables CH Trifluoromethylcyclopropanation

Chemo- and site-selective derivatizations of natural products enabling biological studies

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