Umpolung Phosphorylation of Tyrosine via 1,2-Phospha-Brook Rearrangement

Phosphorylated tyrosine is a fundamental building block of bioactive peptides and proteins. However, the chemoselective phosphorylation of tyrosine over other nucleophilic amino acid residues in unprotected peptides remains a significant challenge. Here we report an umpolung strategy that converts t...

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Bibliographic Details
Published in:Organic letters 2024-10, Vol.26 (41), p.8827-8831
Main Authors: Fukuta, Tomoyuki, Tatsumi, Toshifumi, Fujiyoshi, Kohei, Koyama, Takashi, Kawashima, Shigehiro A., Mitsunuma, Harunobu, Yamatsugu, Kenzo, Kanai, Motomu
Format: Article
Language:English
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Summary:Phosphorylated tyrosine is a fundamental building block of bioactive peptides and proteins. However, the chemoselective phosphorylation of tyrosine over other nucleophilic amino acid residues in unprotected peptides remains a significant challenge. Here we report an umpolung strategy that converts the C-terminal tyrosine into an electrophilic spirolactone cyclohexadienone motif through hypervalent iodine oxidation, followed by a 1,2-phospha-Brook rearrangement using phosphite diesters as nucleophilic phosphoryl donors. This reaction proceeds chemoselectively at the tyrosine phenol and is applicable to a wide range of peptide substrates containing various nucleophilic amino acid residues, including serine and threonine.
ISSN:1523-7060
1523-7052
1523-7052
DOI:10.1021/acs.orglett.4c03223