Stereoselective synthesis of a phosphonate pThr mimetic via palladium-catalyzed γ-C(sp 3 )-H activation for peptide preparation

We report a facile synthetic strategy toward CH2-substituted phosphothreonine mimetics. Herein, inexpensive valine with a directing group was converted into homothreonine via palladium-catalyzed γ-methyl C(sp3)-H bond activation, followed by construction of a phosphorus-carbon bond via the well-deve...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2019-02, Vol.17 (8), p.2099-2102
Main Authors: Duan, Hua-Zhen, Chen, Hong-Xue, Yu, Qing, Hu, Jun, Li, Yan-Mei, Chen, Yong-Xiang
Format: Article
Language:English
Subjects:
Activation
Hydrogen bonds
Palladium
Phosphoproteins
Phosphorus
Solid phase methods
Solid phase synthesis
Solid phases
Stereoselectivity
Valine
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Summary:We report a facile synthetic strategy toward CH2-substituted phosphothreonine mimetics. Herein, inexpensive valine with a directing group was converted into homothreonine via palladium-catalyzed γ-methyl C(sp3)-H bond activation, followed by construction of a phosphorus-carbon bond via the well-developed Appel reaction and Michaelis-Becker reaction with a total yield of 30%. Furthermore, the derived mimetic was applied for solid-phase synthesis of two phosphopeptide inhibitors. This efficient synthesis provides a chance to prepare not only phosphopeptides but also phosphoproteins resistant to phosphatases.
ISSN:1477-0520
1477-0539
DOI:10.1039/c8ob02999g