Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Isotope Science Center, The University of Tokyo, Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
Org Lett. 2024 Oct 18;26(41):8827-8831. doi: 10.1021/acs.orglett.4c03223. Epub 2024 Oct 10.
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.
磷酸化酪氨酸是生物活性肽和蛋白质的基本结构单元。然而，在未保护的肽中，酪氨酸相对于其他亲核氨基酸残基的化学选择性磷酸化仍然是一个重大挑战。在这里，我们报告了一种反转策略，通过高价碘氧化将 C 末端酪氨酸转化为亲电螺环内酯环己二烯酮基序，然后使用亚磷酸二酯作为亲核磷酰供体进行 1,2-膦a-Brook 重排。该反应在酪氨酸酚上具有化学选择性，适用于包含各种亲核氨基酸残基（包括丝氨酸和苏氨酸）的各种肽底物。
