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. 2023 Nov 30;28(23):7869.
doi: 10.3390/molecules28237869.

Photoinduced Synthesis of Sulfonyl-Containing Phosphorothioates via a Three-Component Reaction

Xianda Wu  1 , Minghong Chen  2 , Shuiyun Zheng  2 , Jie Wu  2   3   4 , Gang Liu  1 , Fu-Sheng He  2
Affiliations

Photoinduced Synthesis of Sulfonyl-Containing Phosphorothioates via a Three-Component Reaction

Xianda Wu et al. Molecules. .

Abstract

Both sulfonyl and phosphorothioate are important privileged structural motifs which are widely presented in pharmaceuticals and agrochemicals. Herein, we describe an efficient approach to synthesizing sulfonyl-containing phosphorothioates by merging photoredox and copper catalysis at room temperature. This protocol is compatible with a wide range of substrates and can be applied to the late-stage modification of complex molecules. Control experiments are conducted to demonstrate the generation of the sulfonyl radical in the transformation.

Keywords: alkene difunctionalization; copper; multicomponent reaction; phosphorothioate; photoredox catalysis; sulfonyl.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Scheme 1
Scheme 1
The development of alkene thiosulfonylation.
Figure 1
Figure 1
Substrate scope for the photoinduced synthesis of sulfonyl-containing phosphorothioates a,b. a Reactions conditions: alkene 1 (0.2 mmol), sulfonyl chloride 2 (0.4 mmol), phosphorothioate 3 (0.4 mmol), Ir(ppy)3 (2 mol%), Cu(OTf)2 (5 mol%), K2HPO4 (0.4 mmol), DCE (2 mL), irradiation with 30 W blue LEDs at room temperature for 12 h. b Isolated yield based on alkene 1.
Scheme 2
Scheme 2
Late-stage functionalization of bioactive molecules.
Scheme 3
Scheme 3
Control experiments.
Scheme 4
Scheme 4
Proposed reaction mechanism.
See this image and copyright information in PMC

References

    1. Li N.S., Frederiksen J.K., Piccirilli J.A. Synthesis, Properties, and Applications of Oligonucleotides Containing an RNA Dinucleotide Phosphorothiolate Linkage. Acc. Chem. Res. 2011;44:1257–1269. doi: 10.1021/ar200131t. - DOI - PMC - PubMed
    1. Kumar T.S., Yang T., Mishra S., Cronin C., Chakraborty S., Shen J.-B., Liang B.T., Jacobson K.A. 5′-Phosphate and 5′-Phosphonate Ester Derivatives of (N)-Methanocarba Adenosine with in Vivo Cardioprotective Activity. J. Med. Chem. 2013;56:902–914. doi: 10.1021/jm301372c. - DOI - PMC - PubMed
    1. Yan H., Wang X., KuoLee R., Chen W. Synthesis and immunostimulatory properties of the phosphorothioate analogues of cdiGMP. Bioorg. Med. Chem. Lett. 2008;18:5631–5634. doi: 10.1016/j.bmcl.2008.08.088. - DOI - PubMed
    1. Cogoi S., Rapozzi V., Quadrifoglio F., Xodo L. Anti-gene Effect in Live Cells of AG Motif Triplex-Forming Oligonucleotides Containing an Increasing Number of Phosphorothioate Linkages. Biochemistry. 2001;40:1135–1143. doi: 10.1021/bi0012639. - DOI - PubMed
    1. Milligan J.F., Uhlenbeck O.C. Determination of RNA-protein contacts using thiophosphate substitutions. Biochemistry. 1989;28:2849–2855. doi: 10.1021/bi00433a016. - DOI - PubMed

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