Introducing covalent warheads on spirocyclic sp2–sp3 fragments by innate C–H functionalization

文献情報

出版日 2023-11-15

DOI 10.1039/D3OB01746J

インパクトファクター 3.876

著者

Christophe Giorgiutti, Thomas Fessard, Quentin Lefebvre

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要旨

Sp2–sp3 fragments play a vital role in fragment-based drug design (FBDD). Strategies to chemically modify them and efficiently access libraries of these compounds have been goals of the highest priority in the last decades. In this work, a series of sp2–sp3 fragments was synthesized and validated for that purpose, based on their measured physical–chemical properties. Selective C–H cyanation and allylation of these fragments was demonstrated by simple heating in presence of an appropriate hydrogen-atom transfer reagent and a radical acceptor. These conditions enabled a streamlined access to covalent fragments in a single step, by direct introduction of the desired covalent binder. Preliminary results on vinylation, as well as late-stage functionalization of a drug analogue were disclosed.

掲載誌

Organic & Biomolecular Chemistry

CiteScore: 3.4

自己引用率: 10.3%

年間論文数: 1041

Organic & Biomolecular Chemistry (OBC) publishes original and high impact research and reviews in organic chemistry. We welcome research that shows new or significantly improved protocols or methodologies in total synthesis, synthetic methodology or physical and theoretical organic chemistry as well as research that shows a significant advance in the organic chemistry or molecular design aspects of chemical biology, catalysis, supramolecular and macromolecular chemistry, theoretical chemistry, mechanism-oriented physical organic chemistry, medicinal chemistry or natural products. Articles published in the journal should report new work which makes a highly-significant impact in the field. Routine and incremental work is generally not suitable for publication in the journal. More details about key areas of our scope are below. In all cases authors should include in their article clear rationale for why their research has been carried out.