Additive-controlled asymmetric iodocyclization enables enantioselective access to both α- and β-nucleosides
β-Nucleosides and their analogs are dominant clinically-used antiviral and antitumor drugs. α-Nucleosides, the anomers of β-nucleosides, exist in nature and have significant potential as drugs or drug carriers. Currently, the most widely used methods for synthesizing β- and α-nucleosides are via N -...
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Veröffentlicht in: | Nature communications 2023-01, Vol.14 (1), p.138-138, Article 138 |
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Sprache: | eng |
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Zusammenfassung: | β-Nucleosides and their analogs are dominant clinically-used antiviral and antitumor drugs. α-Nucleosides, the anomers of β-nucleosides, exist in nature and have significant potential as drugs or drug carriers. Currently, the most widely used methods for synthesizing β- and α-nucleosides are via
N
-glycosylation and pentose aminooxazoline, respectively. However, the stereoselectivities of both methods highly depend on the assisting group at the C2’ position. Herein, we report an additive-controlled stereodivergent iodocyclization method for the selective synthesis of α- or β-nucleosides. The stereoselectivity at the anomeric carbon is controlled by the additive (NaI for β-nucleosides; PPh
3
S for α-nucleosides). A series of β- and α-nucleosides are prepared in high yields (up to 95%) and stereoselectivities (β:α up to 66:1, α:β up to 70:1). Notably, the introduced iodine at the C2’ position of the nucleoside is readily functionalized, leading to multiple structurally diverse nucleoside analogs, including stavudine, an FDA-approved anti-HIV agent, and molnupiravir, an FDA-approved anti-SARS-CoV-2 agent.
Nucleosides and their analogs are pharmacologically important molecules. Here, the authors report an additive-controlled stereodivergent iodocyclization method for the selective synthesis of α- or β-nucleosides. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-022-35610-w |